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Multiple Investigator Sponsored Studies Support the Potential of BLINCYTO® (blinatumomab) Across Acute Lymphoblastic Leukemia Treatment Paradigm New Data Reinforce KYPROLIS® (carfilzomib) as an Important Treatment Option for Relapsed or Refractory Multiple Myeloma Additional Analyses Support Eculizumab (a biosimilar candidate to SOLIRIS®) as a Potential Option in Paroxysmal Nocturnal Hemoglobinuria THOUSAND OAKS, Calif., Dec. 8, 2023 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced the presentation of new data from its blood cancer portfolio and pipeline at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition, taking place from Dec. 9-12 in San Diego. "Data at this year's ASH meeting illustrate the expanding potential of our innovative hematology medicines, BLINCYTO and KYPROLIS, as well as our commitment to providing additional treatment options with our biosimilar eculizumab," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "As the pioneer of T-cell engager technology and building on nearly a decade of real-world experience, we continue to advance our first-in-class BiTE® molecule, BLINCYTO, into earlier lines of treatment where we have seen encouraging data in patients living with acute lymphoblastic leukemia." Abstracts are available on the ASH website. Key Abstracts and Presentation Times: Amgen Sponsored Abstracts KYPROLIS® (carfilzomib) Real-World Outcomes for Relapsed or Refractory Multiple Myeloma Patients Treated with Lenalidomide and Daratumumab Sparing Triplet Regimens: A United States Retrospective Cohort Study Abstract #4705, Session #652, Monday, December 11 from 6:00 - 8:00 p.m. PT Eculizumab ( investigational biosimilar ABP 959 candidate to SOLIRIS®) Efficacy of Parallel and Crossover Analysis As Well As Pharmacokinetic Similarity Were Confirmed between ABP 959 and Eculizumab Reference Product in Patients with PNH Abstract #4092, Session #508, Monday, December 11 from 6:00 - 8:00 p.m. PT Investigator Sponsored Studies BLINCYTO® (blinatumomab) Chemotherapy-Free Combination of Blinatumomab and Ponatinib in Adults With Newly Diagnosed Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia: Updates From a Phase II Trial Abstract #2827, Session #612, Sunday, December 10 from 6:00 - 8:00 p.m. PT Phase II Study of Low-Intensity Chemotherapy (Mini-Hyper-CVD) and Ponatinib Followed by Blinatumomab and Ponatinib in Patients With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Abstract #2868, Session #614, Sunday, December 10 from 6:00 - 8:00 p.m. PT Assessment of Outcomes of Consolidation Therapy By Number of Cycles of Blinatumomab Received in Newly Diagnosed Measurable Residual Disease Negative Patients with B-Lineage Acute Lymphoblastic Leukemia: In the ECOG-ACRIN E1910 Randomized Phase III National Clinical Trials Network Trial* Abstract #2877, Session #614, Sunday, December 10 from 6:00 - 8:00 p.m. PT Phase 2 Trial of Mini-Hyper-CVD Plus Inotuzumab Ozogamicin, With or Without Blinatumomab, in Older Patients With Newly Diagnosed Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia Abstract #2878, Session #614, Sunday, December 10 from 6:00 - 8:00 p.m. PT Pediatric Patients with High-Risk B-Cell ALL in First Complete Remission May Benefit from Less Toxic Immunotherapy with Blinatumomab – Results from Randomized Controlled Phase 3 Trial AIEOP-BFM ALL 2017 Abstract #825, Session #614, Monday, December 11 from 2:45 - 4:15 p.m. PT Dose Reduced Chemotherapy in Sequence with Blinatumomab for Newly Diagnosed Older Patients with Ph/BCR::ABL Negative B-Precursor Adult Lymphoblastic Leukemia (ALL): Preliminary Results of the GMALL Bold Trial Abstract #964, Session #614, Monday, December 11 from 4:30 - 6:00 p.m. PT Updated Results from a Phase II Study of Hyper-CVAD, with or without Inotuzumab Ozogamicin, and Sequential Blinatumomab in Patients with Newly Diagnosed B-cell Acute Lymphoblastic Leukemia Abstract #4245, Session #614, Monday, December 11 from 6:00 - 8:00 p.m. PT Comparison between Dasatinib-Blinatumomab Vs Ponatinib-Blinatumomab Chemo-Free Strategy for Newly Diagnosed Ph+ Acute Lymphoblastic Leukemia Patients. Preliminary Results of the Gimema ALLL2820 Trial Abstract #4249, Session #614, Monday, December 11 from 6:00 - 8:00 p.m. PT *E1910 is sponsored by National Cancer Institute (NCI), part of the National Institutes of Health, and conducted by the NCI Funded National Clinical Trial Network. KYPROLIS® (carfilzomib) Carfilzomib-Lenalidomide-Dexamethasone (KRd) Vs. Lenalidomide-Dexamethasone (Rd) in Newly Diagnosed Fit or Intermediate-Fit Multiple Myeloma Patients Not Eligible for Autologous Stem-Cell Transplantation (Phase III EMN20 Trial): Analysis of Sustained Undetectable Minimal Residual Disease (MRD) Abstract #205, Session #653, Saturday, December 9 from 2:00 - 3:30 p.m. PT Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone Induction and Consolidation with Tandem Transplant in High-Risk Newly Diagnosed Myeloma Patients: Final Results of the Phase 2 Study IFM 2018-04 Abstract #207, Session #653, Saturday, December 9 from 2:00 - 3:30 p.m. PT GEM2017FIT Trial: Induction Therapy with Bortezomib-Melphalan and Prednisone (VMP) Followed By Lenalidomide and Dexamethasone (Rd) Versus Carfilzomib, Lenalidomide and Dexamethasone (KRd) Plus/Minus Daratumumab (D), 18 Cycles, Followed By Consolidation and Maintenance Therapy with Lenalidomide and Daratumumab: Phase III, Multicenter, Randomized Trial for Elderly Fit Newly Diagnosed Multiple Myeloma (NDMM) Patients Aged between 65 and 80 Years Abstract #209, Session #653, Saturday, December 9 from 2:00 - 3:30 p.m. PT Results of the Phase III Randomized Iskia Trial: Isatuximab-Carfilzomib-Lenalidomide-Dexamethasone Vs Carfilzomib-Lenalidomide-Dexamethasone As Pre-Transplant Induction and Post-Transplant Consolidation in Newly Diagnosed Multiple Myeloma Patients Abstract #4, Plenary Scientific Session, Sunday, December 10 from 2:00 - 4:00 p.m. PT About BLINCYTO® (blinatumomab) BLINCYTO is a BiTE® (bispecific T-cell engager) immuno-oncology therapy that targets CD19 surface antigens on B cells. BiTE molecules fight cancer by helping the body's immune system detect and target malignant cells by engaging T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. By bringing T cells near cancer cells, the T cells can inject toxins and trigger cancer cell death (apoptosis). BiTE immuno-oncology therapies are currently being investigated for their potential to treat a wide variety of cancers. BLINCYTO was granted breakthrough therapy and priority review designations by the U.S. Food and Drug Administration and is approved in the U.S. for the treatment of: CD19-positive B-cell precursor ALL in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1% in adults and pediatric patients. relapsed or refractory CD19-positive B-cell precursor ALL in adults and pediatric patients. In the European Union (EU), BLINCYTO is indicated as monotherapy for the treatment of: adults with Philadelphia chromosome-negative CD19 positive relapsed or refractory B-precursor acute lymphoblastic leukemia (ALL). Patients with Philadelphia chromosome-positive B-precursor ALL should have failed treatment with at least 2 tyrosine kinase inhibitors (TKIs) and have no alternative treatment options. adults with Philadelphia chromosome-negative CD19 positive B-precursor ALL in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1%. pediatric patients aged 1 year or older with Philadelphia chromosome-negative CD19 positive B-precursor ALL which is refractory or in relapse after receiving at least two prior therapies or in relapse after receiving prior allogeneic hematopoietic stem cell transplantation. pediatric patients aged 1 year or older with high-risk first relapsed Philadelphia chromosome-negative CD19 positive B-precursor ALL as part of the consolidation therapy. BLINCYTO® IMPORTANT SAFETY INFORMATION WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving BLINCYTO®. Interrupt or discontinue BLINCYTO® and treat with corticosteroids as recommended. Neurological toxicities, which may be severe, life-threatening or fatal, occurred in patients receiving BLINCYTO®. Interrupt or discontinue BLINCYTO® as recommended. Contraindications BLINCYTO® is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation. Warnings and Precautions Cytokine Release Syndrome (CRS): CRS, which may be life-threatening or fatal, occurred in 15% of patients with R/R ALL and in 7% of patients with MRD-positive ALL. The median time to onset of CRS is 2 days after the start of infusion and the median time to resolution of CRS was 5 days among cases that resolved. Closely monitor and advise patients to contact their healthcare professional for signs and symptoms of serious adverse events such as fever, headache, nausea, asthenia, hypotension, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased total bilirubin (TBILI), and disseminated intravascular coagulation (DIC). The manifestations of CRS after treatment with BLINCYTO® overlap with those of infusion reactions, capillary leak syndrome, and hemophagocytic histiocytosis/macrophage activation syndrome. If severe CRS occurs, interrupt BLINCYTO® until CRS resolves. Discontinue BLINCYTO® permanently if life-threatening CRS occurs. Administer corticosteroids for severe or life-threatening CRS. Neurological Toxicities: Approximately 65% of patients receiving BLINCYTO® in clinical trials experienced neurological toxicities. The median time to the first event was within the first 2 weeks of BLINCYTO® treatment and the majority of events resolved. The most common (≥ 10%) manifestations of neurological toxicity were headache and tremor. Severe, life–threatening, or fatal neurological toxicities occurred in approximately 13% of patients, including encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders. Manifestations of neurological toxicity included cranial nerve disorders. Monitor patients for signs or symptoms and interrupt or discontinue BLINCYTO® as outlined in the PI. Infections: Approximately 25% of patients receiving BLINCYTO® in clinical trials experienced serious infections such as sepsis, pneumonia, bacteremia, opportunistic infections, and catheter-site infections, some of which were life-threatening or fatal. Administer prophylactic antibiotics and employ surveillance testing as appropriate during treatment. Monitor patients for signs or symptoms of infection and treat appropriately, including interruption or discontinuation of BLINCYTO® as needed. Tumor Lysis Syndrome (TLS), which may be life-threatening or fatal, has been observed. Preventive measures, including pretreatment nontoxic cytoreduction and on-treatment hydration, should be used during BLINCYTO® treatment. Monitor patients for signs and symptoms of TLS and interrupt or discontinue BLINCYTO® as needed to manage these events. Neutropenia and Febrile Neutropenia, including life-threatening cases, have been observed. Monitor appropriate laboratory parameters (including, but not limited to, white blood cell count and absolute neutrophil count) during BLINCYTO® infusion and interrupt BLINCYTO® if prolonged neutropenia occurs. Effects on Ability to Drive and Use Machines: Due to the possibility of neurological events, including seizures, patients receiving BLINCYTO® are at risk for loss of consciousness, and should be advised against driving and engaging in hazardous occupations or activities such as operating heavy or potentially dangerous machinery while BLINCYTO® is being administered. Elevated Liver Enzymes: Transient elevations in liver enzymes have been associated with BLINCYTO® treatment with a median time to onset of 3 days. In patients receiving BLINCYTO®, although the majority of these events were observed in the setting of CRS, some cases of elevated liver enzymes were observed outside the setting of CRS, with a median time to onset of 19 days. Grade 3 or greater elevations in liver enzymes occurred in approximately 7% of patients outside the setting of CRS and resulted in treatment discontinuation in less than 1% of patients. Monitor ALT, AST, gamma-glutamyl transferase, and TBILI prior to the start of and during BLINCYTO® treatment. BLINCYTO® treatment should be interrupted if transaminases rise to > 5 times the upper limit of normal (ULN) or if TBILI rises to > 3 times ULN. Pancreatitis: Fatal pancreatitis has been reported in patients receiving BLINCYTO® in combination with dexamethasone in clinical trials and the post-marketing setting. Evaluate patients who develop signs and symptoms of pancreatitis and interrupt or discontinue BLINCYTO® and dexamethasone as needed. Leukoencephalopathy: Although the clinical significance is unknown, cranial magnetic resonance imaging (MRI) changes showing leukoencephalopathy have been observed in patients receiving BLINCYTO®, especially in patients previously treated with cranial irradiation and antileukemic chemotherapy. Preparation and administration errors have occurred with BLINCYTO® treatment. Follow instructions for preparation (including admixing) and administration in the PI strictly to minimize medication errors (including underdose and overdose). Immunization: Vaccination with live virus vaccines is not recommended for at least 2 weeks prior to the start of BLINCYTO® treatment, during treatment, and until immune recovery following last cycle of BLINCYTO®. Benzyl Alcohol Toxicity in Neonates: Serious adverse reactions, including fatal reactions and the "gasping syndrome", have been reported in very low birth weight (VLBW) neonates born weighing less than 1500 g, and early preterm neonates (infants born less than 34 weeks gestational age) who received intravenous drugs containing benzyl alcohol as a preservative. Early preterm VLBW neonates may be more likely to develop these reactions, because they may be less able to metabolize benzyl alcohol. Use the preservative-free preparations of BLINCYTO® where possible in neonates. When prescribing BLINCYTO® (with preservative) for neonatal patients, consider the combined daily metabolic load of benzyl alcohol from all sources including BLINCYTO® (with preservative), other products containing benzyl alcohol or other excipients (e.g., ethanol, propylene glycol) which compete with benzyl alcohol for the same metabolic pathway. Monitor neonatal patients receiving BLINCYTO® (with preservative) for new or worsening metabolic acidosis. The minimum amount of benzyl alcohol at which serious adverse reactions may occur in neonates is not known. The BLINCYTO® 7-Day bag (with preservative) contains 7.4 mg of benzyl alcohol per mL. Embryo-Fetal Toxicity: Based on its mechanism of action, BLINCYTO® may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with BLINCYTO® and for 48 hours after the last dose. Adverse Reactions The most common adverse reactions (≥ 20%) are pyrexia, infusion-related reactions, infections (pathogen unspecified), headache, neutropenia, anemia, and thrombocytopenia. Dosage and Administration Guidelines BLINCYTO® is administered as a continuous intravenous infusion at a constant flow rate using an infusion pump which should be programmable, lockable, non-elastomeric, and have an alarm. It is very important that the instructions for preparation (including admixing) and administration provided in the full Prescribing Information are strictly followed to minimize medication errors (including underdose and overdose). INDICATIONS BLINCYTO® (blinatumomab) is indicated for the treatment of CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1% in adult and pediatric patients. BLINCYTO® is indicated for the treatment of relapsed or refractory CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in adult and pediatric patients. Please see BLINCYTO® full Prescribing Information , including BOXED WARNINGS. About BiTE® Technology BiTE® (bispecific T-cell engager) technology is a targeted immuno-oncology platform that is designed to engage patient's own T cells to any tumor-specific antigen, activating the cytotoxic potential of T cells to eliminate detectable cancer. The BiTE immuno-oncology platform has the potential to treat different tumor types through tumor-specific antigens. The BiTE platform has a goal of leading to off-the-shelf solutions, which have the potential to make innovative T cell treatment available to all providers when their patients need it. Amgen is advancing more than a dozen BiTE molecules across a broad range of hematologic malignancies and solid tumors, further investigating BiTE technology with the goal of enhancing patient experience and therapeutic potential. To learn more about BiTE technology, visit . About KYPROLIS® (carfilzomib) Proteasomes play an important role in cell function and growth by breaking down proteins that are damaged or no longer needed.1 KYPROLIS has been shown to block proteasomes, leading to an excessive build-up of proteins within cells.2 In some cells, KYPROLIS can cause cell death, especially in myeloma cells because they are more likely to contain a higher amount of abnormal proteins.1,2 Since its first approval in 2012, more than 285,000 patients worldwide have received KYPROLIS. KYPROLIS is approved in the U.S. for the following: for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy in combination with Lenalidomide and dexamethasone; or Dexamethasone; or Daratumumab and dexamethasone. Daratumumab and hyaluronidase-fihj and dexamethasone; or Isatuximab and dexamethasone as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy. KYPROLIS is also approved in Algeria, Argentina, Australia, Bahrain, Belarus, Brazil, Canada, Chile, Colombia, Ecuador, Egypt, European Union, Hong Kong, India, Israel, Japan, Jordan, Kazakhstan, Kuwait, Lebanon, Macao, Malaysia, Mexico, Morocco, New Zealand, Oman, Peru, Philippines, Qatar, Russia, Saudi Arabia, Serbia, Singapore, S. Africa, S. Korea, Switzerland, Taiwan, Thailand, Turkey and United Arab Emirates. KYPROLIS® IMPORTANT SAFETY INFORMATION Cardiac Toxicities New onset or worsening of pre-existing cardiac failure (e.g., congestive heart failure, pulmonary edema, decreased ejection fraction), cardiomyopathy, myocardial ischemia, and myocardial infarction including fatalities have occurred following administration of KYPROLIS®. Some events occurred in patients with normal baseline ventricular function. Death due to cardiac arrest has occurred within one day of administration. Monitor patients for signs or symptoms of cardiac failure or ischemia. Evaluate promptly if cardiac toxicity is suspected. Withhold KYPROLIS® for Grade 3 or 4 cardiac adverse reactions until recovery, and consider whether to restart at 1 dose level reduction based on a benefit/risk assessment. While adequate hydration is required prior to each dose in Cycle 1, monitor all patients for evidence of volume overload, especially patients at risk for cardiac failure. Adjust total fluid intake as clinically appropriate. For patients ≥ 75 years, the risk of cardiac failure is increased. Patients with New York Heart Association Class III and IV heart failure, recent myocardial infarction, conduction abnormalities, angina, or arrhythmias may be at greater risk for cardiac complications and should have a comprehensive medical assessment prior to starting treatment with KYPROLIS® and remain under close follow-up with fluid management. Acute Renal Failure Cases of acute renal failure, including some fatal renal failure events, and renal insufficiency (including renal failure) have occurred. Acute renal failure was reported more frequently in patients with advanced relapsed and refractory multiple myeloma who received KYPROLIS® monotherapy. Monitor renal function with regular measurement of the serum creatinine and/or estimated creatinine clearance. Reduce or withhold dose as appropriate. Tumor Lysis Syndrome Cases of Tumor Lysis Syndrome (TLS), including fatal outcomes, have occurred. Patients with a high tumor burden should be considered at greater risk for TLS. Adequate hydration is required prior to each dose in Cycle 1, and in subsequent cycles as needed. Consider uric acid lowering drugs in patients at risk for TLS. Monitor for evidence of TLS during treatment and manage promptly, and withhold until resolved. Pulmonary Toxicity Acute Respiratory Distress Syndrome (ARDS), acute respiratory failure, and acute diffuse infiltrative pulmonary disease such as pneumonitis and interstitial lung disease have occurred. Some events have been fatal. In the event of drug-induced pulmonary toxicity, discontinue KYPROLIS®. Pulmonary Hypertension Pulmonary arterial hypertension (PAH) was reported. Evaluate with cardiac imaging and/or other tests as indicated. Withhold KYPROLIS® for PAH until resolved or returned to baseline and consider whether to restart based on a benefit/risk assessment. Dyspnea Dyspnea was reported in patients treated with KYPROLIS®. Evaluate dyspnea to exclude cardiopulmonary conditions including cardiac failure and pulmonary syndromes. Stop KYPROLIS® for Grade 3 or 4 dyspnea until resolved or returned to baseline. Consider whether to restart based on a benefit/risk assessment. Hypertension Hypertension, including hypertensive crisis and hypertensive emergency, has been observed, some fatal. Control hypertension prior to starting KYPROLIS®. Monitor blood pressure regularly in all patients. If hypertension cannot be adequately controlled, withhold KYPROLIS® and evaluate. Consider whether to restart based on a benefit/risk assessment. Venous Thrombosis Venous thromboembolic events (including deep venous thrombosis and pulmonary embolism) have been observed. Provide thromboprophylaxis for patients being treated with the combination of KYPROLIS® with dexamethasone or with lenalidomide plus dexamethasone or with daratumumab and dexamethasone. The thromboprophylaxis regimen should be based on an assessment of the patient's underlying risks. For patients using hormonal contraception associated with a risk of thrombosis, consider an alternative method of effective contraception during treatment. Infusion-Related Reactions Infusion-related reactions, including life-threatening reactions, have occurred. Signs and symptoms include fever, chills, arthralgia, myalgia, facial flushing, facial edema, laryngeal edema, vomiting, weakness, shortness of breath, hypotension, syncope, chest tightness, or angina. These reactions can occur immediately following or up to 24 hours after administration. Premedicate with dexamethasone to reduce the incidence and severity of infusion-related reactions. Hemorrhage Fatal or serious cases of hemorrhage have been reported. Hemorrhagic events have included gastrointestinal, pulmonary, and intracranial hemorrhage and epistaxis. Promptly evaluate signs and symptoms of blood loss. Reduce or withhold dose as appropriate. Thrombocytopenia KYPROLIS® causes thrombocytopenia with recovery to baseline platelet count usually by the start of the next cycle. Monitor platelet counts frequently during treatment. Reduce or withhold dose as appropriate. Hepatic Toxicity and Hepatic Failure Cases of hepatic failure, including fatal cases, have occurred. KYPROLIS® can cause increased serum transaminases. Monitor liver enzymes regularly regardless of baseline values. Reduce or withhold dose as appropriate. Thrombotic Microangiopathy Cases of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), including fatal outcome, have occurred. Monitor for signs and symptoms of TTP/HUS. Discontinue if diagnosis is suspected. If the diagnosis of TTP/HUS is excluded, KYPROLIS® may be restarted. The safety of reinitiating KYPROLIS® is not known. Posterior Reversible Encephalopathy Syndrome (PRES) Cases of PRES have occurred in patients receiving KYPROLIS®. If PRES is suspected, discontinue and evaluate with appropriate imaging. The safety of reinitiating KYPROLIS® is not known. Progressive Multifocal Leukoencephalopathy (PML) Cases of PML, including fatal cases, have occurred. In addition to KYPROLIS®, other contributary factors may include prior or concurrent use of immunosuppressive therapy. Consider PML in any patient with new onset of or changes in pre-existing neurological signs or symptoms. If PML is suspected, discontinue and initiate evaluation for PML including neurology consultation. Increased Fatal and Serious Toxicities in Combination with Melphalan and Prednisone in Newly Diagnosed Transplant-ineligible Patients In a clinical trial of transplant-ineligible patients with newly diagnosed multiple myeloma comparing KYPROLIS®, melphalan, and prednisone (KMP) vs bortezomib, melphalan, and prednisone (VMP), a higher incidence of serious and fatal adverse reactions was observed in patients in the KMP arm. KMP is not indicated for transplant-ineligible patients with newly diagnosed multiple myeloma. Embryo-fetal Toxicity KYPROLIS® can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Females of reproductive potential should use effective contraception during treatment with KYPROLIS® and for 6 months following the final dose. Males of reproductive potential should use effective contraception during treatment with KYPROLIS® and for 3 months following the final dose. Adverse Reactions The most common adverse reactions in the combination therapy trials: anemia, diarrhea, fatigue, hypertension, pyrexia, upper respiratory tract infection, thrombocytopenia, cough, dyspnea, and insomnia. The most common adverse reactions in monotherapy trials: anemia, fatigue, thrombocytopenia, nausea, pyrexia, dyspnea, diarrhea, headache, cough, edema peripheral. Please see accompanying full Prescribing Information. INDICATIONS KYPROLIS® (carfilzomib) is indicated in combination with dexamethasone, or with lenalidomide plus dexamethasone, or with daratumumab plus dexamethasone, or with daratumumab plus hyaluronidase-fihj plus dexamethasone, or with isatuximab plus dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy. KYPROLIS® is indicated as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy. About Amgen Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology. Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential. Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average and is also part of the Nasdaq-100 index. In 2023, Amgen was named one of "America's Greatest Workplaces" by Newsweek, one of "America's Climate Leaders" by USA Today and one of the "World's Best Companies" by TIME. For more information, visit Amgen.com and follow us on X (formerly known as Twitter), LinkedIn, Instagram, TikTok, YouTube and Threads. Amgen Forward-Looking Statements This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen. 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We develop product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as we may have believed at the time of entering into such relationship. Also, we or others could identify safety, side effects or manufacturing problems with our products, including our devices, after they are on the market. Our results may be affected by our ability to successfully market both new and existing products domestically and internationally, clinical and regulatory developments involving current and future products, sales growth of recently launched products, competition from other products including biosimilars, difficulties or delays in manufacturing our products and global economic conditions. In addition, sales of our products are affected by pricing pressure, political and public scrutiny and reimbursement policies imposed by third-party payers, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and healthcare cost containment. Furthermore, our research, testing, pricing, marketing and other operations are subject to extensive regulation by domestic and foreign government regulatory authorities. Our business may be impacted by government investigations, litigation and product liability claims. In addition, our business may be impacted by the adoption of new tax legislation or exposure to additional tax liabilities. If we fail to meet the compliance obligations in the corporate integrity agreement between us and the U.S. government, we could become subject to significant sanctions. Further, while we routinely obtain patents for our products and technology, the protection offered by our patents and patent applications may be challenged, invalidated or circumvented by our competitors, or we may fail to prevail in present and future intellectual property litigation. We perform a substantial amount of our commercial manufacturing activities at a few key facilities, including in Puerto Rico, and also depend on third parties for a portion of our manufacturing activities, and limits on supply may constrain sales of certain of our current products and product candidate development. An outbreak of disease or similar public health threat, such as COVID-19, and the public and governmental effort to mitigate against the spread of such disease, could have a significant adverse effect on the supply of materials for our manufacturing activities, the distribution of our products, the commercialization of our product candidates, and our clinical trial operations, and any such events may have a material adverse effect on our product development, product sales, business and results of operations. We rely on collaborations with third parties for the development of some of our product candidates and for the commercialization and sales of some of our commercial products. In addition, we compete with other companies with respect to many of our marketed products as well as for the discovery and development of new products. Further, some raw materials, medical devices and component parts for our products are supplied by sole third-party suppliers. Certain of our distributors, customers and payers have substantial purchasing leverage in their dealings with us. The discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations. Our efforts to collaborate with or acquire other companies, products or technology, and to integrate the operations of companies or to support the products or technology we have acquired, may not be successful. There can be no guarantee that we will be able to realize any of the strategic benefits, synergies or opportunities arising from the Horizon acquisition, and such benefits, synergies or opportunities may take longer to realize than expected. We may not be able to successfully integrate Horizon, and such acquisition or integration may take longer, be more difficult or cost more than expected. A breakdown, cyberattack or information security breach of our information technology systems could compromise the confidentiality, integrity and availability of our systems and our data. Our stock price is volatile and may be affected by a number of events. Our business and operations may be negatively affected by the failure, or perceived failure, of achieving our environmental, social and governance objectives. The effects of global climate change and related natural disasters could negatively affect our business and operations. Global economic conditions may magnify certain risks that affect our business. Our business performance could affect or limit the ability of our Board of Directors to declare a dividend or our ability to pay a dividend or repurchase our common stock. We may not be able to access the capital and credit markets on terms that are favorable to us, or at all. The scientific information discussed in this news release related to our product candidates is preliminary and investigative. Such product candidates are not approved by the U.S. Food and Drug Administration, and no conclusions can or should be drawn regarding the safety or effectiveness of the product candidates. Further, any scientific information discussed in this news release relating to new indications for our products is preliminary and investigative and is not part of the labeling approved by the U.S. Food and Drug Administration for the products. The products are not approved for the investigational use(s) discussed in this news release, and no conclusions can or should be drawn regarding the safety or effectiveness of the products for these uses. CONTACT: Amgen, Thousand Oaks Elissa Snook, 609-251-1407 (media) Jessica Akopyan, 805-440-5721 (media) Justin Claeys, 805-313-9775 (investors) 1 Moreau P, et al. Blood. 2012;120(5):947-59. 2 Kortuem KM and Stewart AK. Blood. 2013;7;121(6):893. SOURCE Amgen

SHIRLEY, N.Y., Oct. 10, 2023 /PRNewswire/ -- American Regent announces the release and availability of Levocarnitine Injection, USP, FDA-approved, "AP" rated, and therapeutically equivalent to Carnitor®. Levocarnitine is indicated for the acute and chronic treatment of patients with an inborn error of metabolism which results in secondary carnitine deficiency, and for the prevention and treatment of carnitine deficiency in patients with end-stage renal disease who are undergoing dialysis. Continue Reading American Regent announces the release and availability of Levocarnitine Injection, USP. Tweet this Levocarnitine Injection is supplied as a 5 mL single-dose vial, with a strength of 1 gram/5 mL (200 mg/mL), and as a 20 mL single-dose vial, with a strength of 4 grams/20 mL (200 mg/mL) "We are pleased to make this crucial medication available to patients who need it. We are equally pleased to add Levocarnitine Injection to our robust line of products, which are formulated, filled, and finished at our US-based manufacturing facilities," stated Joann Gioia, Vice President and Chief Commercial Officer at American Regent, Inc. This product is available for immediate shipment. Customers can order Levocarnitine Injection, USP, through their wholesaler/distributor, or by contacting our Customer Support Group at 1-800-645-1706. See the following Important Safety Information, in addition to the product's Full Prescribing Information. For additional information, please visit . All trademarks are the property of their respective owners. References: 1. Orange book: Approved drug products with therapeutic equivalence evaluations. U.S. Food & Drug Administration. . Accessed April 27, 2023. PP-LI-US-0006 Levocarnitine Injection, USP For intravenous use only INDICATIONS AND USAGE For the acute and chronic treatment of patients with an inborn error of metabolism which results in secondary carnitine deficiency. For the prevention and treatment of carnitine deficiency in patients with end-stage renal disease who are undergoing dialysis. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS None known. WARNINGS Hypersensitivity Reactions Serious hypersensitivity reactions, including anaphylaxis, laryngeal edema, and bronchospasm have been reported following levocarnitine administration, mostly in patients with end-stage renal disease who are undergoing dialysis. Some reactions occurred within minutes after intravenous administration of levocarnitine. If a severe hypersensitivity reaction occurs, discontinue levocarnitine treatment and initiate appropriate medical treatment. Consider the risks and benefits of re-administering levocarnitine to individual patients following a severe reaction. If the decision is made to re-administer the product, monitor patients for a reoccurrence of signs and symptoms of a severe hypersensitivity reaction. PRECAUTIONS General The safety and efficacy of oral levocarnitine has not been evaluated in patients with renal insufficiency. Chronic administration of high doses of oral levocarnitine in patients with severely compromised renal function or in ESRD patients on dialysis may result in accumulation of the potentially toxic metabolites, trimethylamine and trimethylamine-N-oxide, since these metabolites are normally excreted in the urine. Drug Interactions Reports of INR increase with the use of warfarin have been observed. It is recommended that INR levels be monitored in patients on warfarin therapy after the initiation of treatment with levocarnitine or after dose adjustments. Pregnancy There are no adequate and well-controlled studies in pregnant women. This drug should be used during pregnancy only if clearly needed. Nursing Mothers Levocarnitine supplementation in nursing mothers has not been specifically studied. Studies in dairy cows indicate that the concentration of levocarnitine in milk is increased following exogenous administration of levocarnitine. In nursing mothers receiving levocarnitine, any risks to the child of excess carnitine intake need to be weighed against the benefits of levocarnitine supplementation to the mother. Consideration may be given to discontinuation of nursing or of levocarnitine treatment. ADVERSE REACTIONS Clinical Trials Experience Transient nausea and vomiting have been observed. Less frequent adverse reactions are body odor, nausea, and gastritis. Postmarketing Experience The following adverse reactions have been reported: Neurologic Reactions: Seizures have been reported to occur in patients, with or without pre-existing seizure activity, receiving either oral or intravenous levocarnitine. In patients with pre-existing seizure activity, an increase in seizure frequency and/or severity has been reported. Hypersensitivity reactions: Anaphylaxis, laryngeal edema, and bronchospasm. For additional safety information, please see Full Prescribing Information. You are encouraged to report adverse drug events to American Regent, Inc. at 1-800-734-9236 or to the FDA by visiting or calling 1-800-FDA-1088. REF 1593 11/2022 You are encouraged to report adverse drug events (ADEs) to American Regent: T 1.800.734.9236; E [email protected]; F 1.610.650.0170 ADEs may also be reported to the FDA: 1.800.FDA.1088 or Medical Information: T 1.888.354.4855 (9:00 am–5:00 pm Eastern Time, Monday–Friday) medical information outside of normal business hours that cannot wait until the next business day, please call 1.877.845.6371 About American Regent American Regent, Inc.®, a Daiichi Sankyo Group company, is an industry-leading injectable manufacturer. For over 50 years, American Regent has been developing, manufacturing, and supplying quality generic and branded injectables for healthcare providers. For more than 20 years, we have been a leader in IV iron therapy. American Regent is committed to US-based manufacturing. To that end, over the last several years we have made significant investments in expanding and modernizing our manufacturing facilities in Ohio and New York. This expansion will nearly double our capacity and allow us to better serve our customers now and in the future. Speed counts. Flexibility matters. Reliability and quality are paramount. Because patients should never have to wait for the medications they need. For more information, please visit . About Daiichi Sankyo Group Daiichi Sankyo is dedicated to creating new modalities and innovative medicines by leveraging our world-class science and technology for our purpose "to contribute to the enrichment of quality of life around the world." In addition to our current portfolio of medicines for cancer and cardiovascular disease, Daiichi Sankyo is primarily focused on developing novel therapies for people with cancer as well as other diseases with high unmet medical needs. With more than 100 years of scientific expertise and a presence in more than 20 countries, Daiichi Sankyo and its 16,000 employees around the world draw upon a rich legacy of innovation to realize our 2030 Vision to become an "Innovative Global Healthcare Company Contributing to the Sustainable Development of Society." For more information, please visit: . All trademarks are the property of their respective owners. Reference: 1. Orange book: Approved drug products with therapeutic equivalence evaluations. US Food & Drug Administration. Accessed April 27, 2023. SOURCE American Regent Inc

RARITAN, N.J., September 27, 2023 — The Janssen Pharmaceutical Companies of Johnson & Johnson announced today more than 35 presentations from the Company’s industry-leading multiple myeloma portfolio will be featured at the 20th International Myeloma Society (IMS) Annual Meeting. Presentations will include new and updated data in the treatment of multiple myeloma across all lines of therapy based on clinical data supporting DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj), DARZALEX® (daratumumab), CARVYKTI® (ciltacabtagene autoleucel; cilta-cel), TECVAYLI® (teclistamab-cqyv) and TALVEY™ (talquetamab-tgvs). The research presented at IMS represents Janssen’s 20-year commitment to advance the science of multiple myeloma through a deep understanding of the disease and by delivering an innovative portfolio of first-in-class, complementary immunotherapies and regimens that target the disease in different ways. The entirety of the portfolio is being investigated for use alone or in combination throughout the course of the disease.New and updated data will highlight the effectiveness of DARZALEX® in the treatment of newly diagnosed multiple myeloma (NDMM), and the use of TECVAYLI® and TALVEY™ in patients with triple-class exposed (TCE) relapsed or refractory multiple myeloma (RRMM). Notable additional presentations include analyses of data from the Phase 3 CARTITUDE-4 study of CARVYKTI® in adults with relapsed and lenalidomide-refractory multiple myeloma who received one to three prior lines of therapy, which will be featured in oral presentations. Importantly, a poster presentation will highlight perspectives of hematologist-oncologists and specialist nurses on the challenges experienced in multiple myeloma care for healthcare providers and patients, reflecting insights from the Global Multiple Myeloma Call-to-Action (CTA). The CTA, a Janssen-led initiative, was developed in partnership with a global multidisciplinary council driving toward delivering cures by addressing the greatest areas of unmet need in multiple myeloma.Other key highlights include an oral presentation on the proactive management, education and supportive care of dermatologic toxicities associated with TALVEY™ and an oral presentation focused on preliminary recommendations for prevention and management of infections during treatment with TECVAYLI®. Other notable data include the poster presentation of the efficacy and safety of patient subgroups from MonumenTAL-1 featuring the first look at outcomes for TALVEY™ in subgroups such as high-risk cytogenetics and prior B-cell maturation antigen (BCMA)-directed therapies. “Our largest-ever presence at IMS underscores our commitment to relentlessly innovate and transform the treatment of multiple myeloma by harnessing the power of our portfolio of first- and best-in-class therapies,” said Yusri Elsayed, M.D., M.HSc., Ph.D., Vice President, Disease Area Leader, Hematologic Malignancies, Janssen Research & Development, LLC. "In the last two years, we’ve significantly expanded the treatment landscape with the approvals of CARVYKTI, TECVAYLI and TALVEY — three groundbreaking therapies for patients with relapsed or refractory disease — while also continuing to advance a foundational standard of care treatment option with DARZALEX in the frontline setting. We will continue to progress research and strategies that aim to move from a focus on treating to disease progression to the promise of treating to cure."IMS Data Presentation Highlights  About Multiple MyelomaMultiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.1 In multiple myeloma, these plasma cells change, spread rapidly and replace normal cells in the bone marrow with tumors.2 Multiple myeloma is the third most common blood cancer and remains an incurable disease.3 In 2023, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 people will die from the disease.4 People living with multiple myeloma have a 5-year relative survival rate of 59.8 percent.5 While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels and kidney problems or infections.6,7About DARZALEX FASPRO® and DARZALEX®DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) received U.S. FDA approval in May 2020 and is approved for eight indications in multiple myeloma, three of which are for frontline treatment in newly diagnosed patients who are transplant eligible or ineligible.8 It is the only subcutaneous CD38-directed antibody approved to treat patients with MM. DARZALEX FASPRO® is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE® drug delivery technology.DARZALEX® (daratumumab) received U.S. FDA approval in November 2015 and is approved in eight indications, three of which are in the frontline setting, including newly diagnosed patients who are transplant eligible and ineligible.9DARZALEX® is the first CD38-directed antibody approved to treat multiple myeloma.10 DARZALEX®-based regimens have been used in the treatment of more than 422,000 patients worldwide and more than 68,000 patients in the U.S. alone.In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize daratumumab.Since 2020, the National Comprehensive Cancer Network® (NCCN®) has recommended daratumumab based combination regimens for the treatment of newly diagnosed multiple myeloma and relapsed and refractory multiple myeloma.† For newly diagnosed multiple myeloma, the NCCN® guidelines recommend daratumumab in combination with lenalidomide and dexamethasone as a Category 1 preferred regimen in non-transplant candidates; daratumumab in combination with bortezomib, melphalan, and prednisone as another recommended Category 1 regimen for non-transplant candidates; and daratumumab in combination with bortezomib, thalidomide and dexamethasone as a Category 2A regimen useful in certain circumstances for transplant candidates. In relapsed/refractory myeloma, four daratumumab regimens are listed as Category 1 preferred regimens for early relapses (1-3 prior therapies): daratumumab in combination with lenalidomide and dexamethasone; daratumumab in combination with bortezomib and dexamethasone; daratumumab in combination with carfilzomib and dexamethasone; and daratumumab in combination with pomalidomide and dexamethasone [after one prior therapy including lenalidomide and a proteasome inhibitor (PI)]. The NCCN® also recommends daratumumab in combination with cyclophosphamide, bortezomib and dexamethasone as an other Category 2A regimen for early relapses (1-3 prior therapies) and as monotherapy as a Category 2A regimen useful in certain circumstances for early relapse patients after at least three prior therapies, including a PI and an immunomodulatory agent, or for patients who are double refractory to a PI and an immunomodulatory agent.For more information, visit www.DARZALEX.com.About CARVYKTI®CARVYKTI® (cilta-cel) received U.S. Food and Drug Administration approval in February 2022 for the treatment of adults with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.11 In May 2022, the European Commission granted conditional marketing authorization of CARVYKTI® (cilta-cel) for the treatment of adults with relapsed and refractory multiple myeloma who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody, and have demonstrated disease progression on the last therapy.CARVYKTI® is a BCMA-directed, genetically modified autologous T-cell immunotherapy, which involves reprogramming a patient’s own T-cells with a transgene encoding chimeric antigen receptor (CAR) that directs the CAR positive T-cells to eliminate cells that express BCMA. BCMA is primarily expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B cells and plasma cells. The CARVYKTI® CAR protein features two BCMA-targeting single domains designed to confer high avidity against human BCMA. Upon binding to BCMA-expressing cells, the CAR promotes T-cell activation, expansion, and elimination of target cells.In December 2017, Janssen Biotech, Inc. entered into an exclusive worldwide license and collaboration agreement with Legend Biotech USA, Inc. to develop and commercialize CARVYKTI®.For more information, visit www.CARVYKTI.com.About TALVEY™TALVEY™ (talquetamab-tgvs) received approval from the U.S. FDA in August 2023 as a first-in-class bispecific antibody for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody.12 The European Commission (EC) has granted conditional marketing authorization (CMA) of TALVEY™ ▼ (talquetamab) in August 2023 as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma (RRMM) who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody and have demonstrated disease progression on the last therapy.13TALVEY™ is a bispecific T-cell engaging antibody that binds to the CD3 receptor expressed on the surface of T cells and G protein-coupled receptor class C group 5 member D (GPRC5D), a novel multiple myeloma target which is highly expressed on the surface of multiple myeloma cells and non-malignant plasma cells, as well as some healthy tissues such as epithelial cells of the skin and tongue.For more information, visit www.TALVEY.com.About TECVAYLI®TECVAYLI® (teclistamab-cqyv) received approval from the U.S. FDA in October 2022 as an off-the-shelf (or ready to use) antibody that is administered as a subcutaneous treatment for adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody.14 The European Commission (EC) granted TECVAYLI® conditional marketing authorization (CMA) in August 2022 as monotherapy for the treatment of adult patients with RRMM who have received at three prior therapies, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody, and have demonstrated disease progression since the last therapy.15 In August 2023, the EC granted the approval of a Type II variation application for TECVAYLI®, providing the option for a reduced dosing frequency of 1.5mg/kg every two weeks in patients who have achieved a complete response (CR) or better for a minimum of six months.5 TECVAYLI® is a first-in-class, bispecific T-cell engager antibody therapy which uses innovative science to activate the immune system by binding to the CD3 receptor expressed on the surface of T-cells and to the B-cell maturation antigen (BCMA) expressed on the surface of multiple myeloma cells and some healthy B-lineage cells.16For more information, visit www.TECVAYLI.com.All information below is applicable to the U.S. FDA indications.DARZALEX FASPRO® IMPORTANT SAFETY INFORMATION INDICATIONSDARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) is indicated for the treatment of adult patients with multiple myeloma:CONTRAINDICATIONSDARZALEX FASPRO® is contraindicated in patients with a history of severe hypersensitivity to daratumumab, hyaluronidase, or any of the components of the formulation.WARNINGS AND PRECAUTIONSHypersensitivity and Other Administration ReactionsBoth systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur with DARZALEX FASPRO®. Fatal reactions have been reported with daratumumab-containing products, including DARZALEX FASPRO®.Systemic ReactionsIn a pooled safety population of 898 patients with multiple myeloma (N=705) or light chain (AL) amyloidosis (N=193) who received DARZALEX FASPRO® as monotherapy or in combination, 9% of patients experienced a systemic administration-related reaction (Grade 2: 3.2%, Grade 3: 1%). Systemic administration-related reactions occurred in 8% of patients with the first injection, 0.3% with the second injection, and cumulatively 1% with subsequent injections. The median time to onset was 3.2 hours (range: 4 minutes to 3.5 days). Of the 140 systemic administration-related reactions that occurred in 77 patients, 121 (86%) occurred on the day of DARZALEX FASPRO® administration. Delayed systemic administration-related reactions have occurred in 1% of the patients.Severe reactions included hypoxia, dyspnea, hypertension, tachycardia, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Other signs and symptoms of systemic administration-related reactions may include respiratory symptoms, such as bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, and wheezing, as well as anaphylactic reaction, pyrexia, chest pain, pruritus, chills, vomiting, nausea, hypotension, and blurred vision.Pre-medicate patients with histamine-1 receptor antagonist, acetaminophen, and corticosteroids. Monitor patients for systemic administration-related reactions, especially following the first and second injections. For anaphylactic reaction or life-threatening (Grade 4) administration-related reactions, immediately and permanently discontinue DARZALEX FASPRO®. Consider administering corticosteroids and other medications after the administration of DARZALEX FASPRO® depending on dosing regimen and medical history to minimize the risk of delayed (defined as occurring the day after administration) systemic administration-related reactions.Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with daratumumab-containing products. If ocular symptoms occur, interrupt DARZALEX FASPRO® and seek immediate ophthalmologic evaluation prior to restarting DARZALEX FASPRO®.Local ReactionsIn this pooled safety population, injection-site reactions occurred in 8% of patients, including Grade 2 reactions in 0.7%. The most frequent (>1%) injection-site reaction was injection-site erythema. These local reactions occurred a median of 5 minutes (range: 0 minutes to 6.5 days) after starting administration of DARZALEX FASPRO®. Monitor for local reactions and consider symptomatic management.NeutropeniaDaratumumab may increase neutropenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX FASPRO® until recovery of neutrophils. In lower body weight patients receiving DARZALEX FASPRO®, higher rates of Grade 3-4 neutropenia were observed.ThrombocytopeniaDaratumumab may increase thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Consider withholding DARZALEX FASPRO® until recovery of platelets.Embryo-Fetal ToxicityBased on the mechanism of action, DARZALEX FASPRO® can cause fetal harm when administered to a pregnant woman. DARZALEX FASPRO® may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX FASPRO® and for 3 months after the last dose.The combination of DARZALEX FASPRO® with lenalidomide, thalidomide, or pomalidomide is contraindicated in pregnant women because lenalidomide, thalidomide, and pomalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, thalidomide, or pomalidomide prescribing information on use during pregnancy.Interference With Serological TestingDaratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab administration. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type are not impacted.Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX FASPRO®. Type and screen patients prior to starting DARZALEX FASPRO®.Interference With Determination of Complete ResponseDaratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some DARZALEX FASPRO®-treated patients with IgG kappa myeloma protein.ADVERSE REACTIONSIn multiple myeloma, the most common adverse reaction (≥20%) with DARZALEX FASPRO® monotherapy is upper respiratory tract infection. The most common adverse reactions with combination therapy (≥20% for any combination) include fatigue, nausea, diarrhea, dyspnea, insomnia, headache, pyrexia, cough, muscle spasms, back pain, vomiting, hypertension, upper respiratory tract infection, peripheral sensory neuropathy, constipation, pneumonia, and peripheral edema.The most common hematology laboratory abnormalities (≥40%) with DARZALEX FASPRO® are decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin.Please click here to see the full Prescribing Information.DARZALEX® IMPORTANT SAFETY INFORMATION INDICATIONS DARZALEX® (daratumumab) is indicated for the treatment of adult patients with multiple myeloma:CONTRAINDICATIONS DARZALEX® is contraindicated in patients with a history of severe hypersensitivity (eg, anaphylactic reactions) to daratumumab or any of the components of the formulation.  WARNINGS AND PRECAUTIONS Infusion-Related Reactions DARZALEX® can cause severe and/or serious infusion-related reactions including anaphylactic reactions. These reactions can be life threatening, and fatal outcomes have been reported. In clinical trials (monotherapy and combination: N=2066), infusion-related reactions occurred in 37% of patients with the Week 1 (16 mg/kg) infusion, 2% with the Week 2 infusion, and cumulatively 6% with subsequent infusions. Less than 1% of patients had a Grade 3/4 infusion-related reaction at Week 2 or subsequent infusions. The median time to onset was 1.5 hours (range: 0 to 73 hours). Nearly all reactions occurred during infusion or within 4 hours of completing DARZALEX®. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension and blurred vision. When DARZALEX® dosing was interrupted in the setting of ASCT (CASSIOPEIA) for a median of 3.75 months (range: 2.4 to 6.9 months), upon re-initiation of DARZALEX®, the incidence of infusion-related reactions was 11% for the first infusion following ASCT. Infusion-related reactions occurring at re-initiation of DARZALEX® following ASCT were consistent in terms of symptoms and severity (Grade 3 or 4: <1%) with those reported in previous studies at Week 2 or subsequent infusions. In EQUULEUS, patients receiving combination treatment (n=97) were administered the first 16 mg/kg dose at Week 1 split over two days, ie, 8 mg/kg on Day 1 and Day 2, respectively. The incidence of any grade infusion-related reactions was 42%, with 36% of patients experiencing infusion-related reactions on Day 1 of Week 1, 4% on Day 2 of Week 1, and 8% with subsequent infusions. Pre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt DARZALEX® infusion for reactions of any severity and institute medical management as needed. Permanently discontinue DARZALEX® therapy if an anaphylactic reaction or life-threatening (Grade 4) reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.  To reduce the risk of delayed infusion-related reactions, administer oral corticosteroids to all patients following DARZALEX® infusions. Patients with a history of chronic obstructive pulmonary disease may require additional post-infusion medications to manage respiratory complications. Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with chronic obstructive pulmonary disease. Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with DARZALEX® infusion. If ocular symptoms occur, interrupt DARZALEX® infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX®. Interference With Serological Testing Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab infusion. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type is not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX®. Type and screen patients prior to starting DARZALEX®. Neutropenia and Thrombocytopenia DARZALEX® may increase neutropenia and thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX® until recovery of neutrophils or for recovery of platelets.Interference With Determination of Complete Response Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein. Embryo-Fetal Toxicity Based on the mechanism of action, DARZALEX® can cause fetal harm when administered to a pregnant woman. DARZALEX® may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX® and for 3 months after the last dose. The combination of DARZALEX® with lenalidomide, pomalidomide, or thalidomide is contraindicated in pregnant women because lenalidomide, pomalidomide, and thalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, pomalidomide, or thalidomide prescribing information on use during pregnancy. ADVERSE REACTIONS The most frequently reported adverse reactions (incidence ≥20%) were: upper respiratory infection, neutropenia, infusion related reactions, thrombocytopenia, diarrhea, constipation, anemia, peripheral sensory neuropathy, fatigue, peripheral edema, nausea, cough, pyrexia, dyspnea, and asthenia. The most common hematologic laboratory abnormalities (≥40%) with DARZALEX® are: neutropenia, lymphopenia, thrombocytopenia, leukopenia, and anemia.  Please click here to see the full Prescribing Information. CARVYKTI® IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONSCytokine Release Syndrome (CRS) including fatal or life-threatening reactions, occurred following treatment with CARVYKTI® in 95% (92/97) of patients receiving ciltacabtagene autoleucel. Grade 3 or higher CRS (2019 ASTCT grade) occurred in 5% (5/97) of patients, with Grade 5 CRS reported in 1 patient. The median time to onset of CRS was 7 days (range: 112 days). The most common manifestations of CRS included pyrexia (100%), hypotension (43%), increased aspartate aminotransferase (AST) (22%), chills (15%), increased alanine aminotransferase (ALT) (14%) and sinus tachycardia (11%). Grade 3 or higher events associated with CRS included increased AST and ALT, hyperbilirubinemia, hypotension, pyrexia, hypoxia, respiratory failure, acute kidney injury, disseminated intravascular coagulation and hemorrhage, HLH/MAS, angina pectoris, supraventricular and ventricular tachycardia, malaise, myalgias, increased Creactive protein, ferritin, blood alkaline phosphatase and gamma-glutamyl transferase.Identify CRS based on clinical presentation. Evaluate for and treat other causes of fever, hypoxia, and hypotension. CRS has been reported to be associated with findings of HLH/MAS, and the physiology of the syndromes may overlap. HLH/MAS is a potentially life-threatening condition. In patients with progressive symptoms of CRS or refractory CRS despite treatment, evaluate for evidence of HLH/MAS. One patient with CRS and suspected HLH/MAS developed a fatal retroperitoneal hemorrhage in the setting of thrombocytopenia, coagulopathy and anticoagulation.Sixty-nine of 97 (71%) patients received tocilizumab and/or a corticosteroid for CRS after infusion of ciltacabtagene autoleucel. Forty-four (45%) patients received only tocilizumab, of whom 33 (34%) received a single dose and 11 (11%) received more than one dose; 24 patients (25%) received tocilizumab and a corticosteroid, and one patient (1%) received only corticosteroids. Ensure that a minimum of two doses of tocilizumab are available prior to infusion of CARVYKTI®.Monitor patients at least daily for 10 days following CARVYKTI® infusion at a REMS-certified healthcare facility for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for at least 4 weeks after infusion. At the first sign of CRS, immediately institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids.Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time.Neurologic toxicities, which may be severe, life-threatening or fatal, occurred following treatment with CARVYKTI®. Neurologic toxicities included ICANS, neurologic toxicity with signs and symptoms of parkinsonism, Guillain-Barré Syndrome, immune mediated myelitis, peripheral neuropathies, and cranial nerve palsies. Counsel patients on the signs and symptoms of these neurologic toxicities, and on the delayed nature of onset of some of these toxicities. Instruct patients to seek immediate medical attention for further assessment and management if signs or symptoms of any of these neurologic toxicities occur at any time.Overall, one or more subtypes of neurologic toxicity described below occurred following ciltacabtagene autoleucel in 26% (25/97) of patients, of which 11% (11/97) of patients experienced Grade 3 or higher events. These subtypes of neurologic toxicities were also observed in two ongoing studies.Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS): Patients may experience fatal or life-threatening ICANS following treatment with CARVYKTI®, including before CRS onset, concurrently with CRS, after CRS resolution, or in the absence of CRS. ICANS occurred in 23% (22/97) of patients receiving ciltacabtagene autoleucel including Grade 3 or 4 events in 3% (3/97) and Grade 5 (fatal) events in 2% (2/97). The median time to onset of ICANS was 8 days (range 1-28 days). All 22 patients with ICANS had CRS. The most frequent (≥5%) manifestation of ICANS included encephalopathy (23%), aphasia (8%) and headache (6%).Monitor patients at least daily for 10 days following CARVYKTI® infusion at the REMS certified healthcare facility for signs and symptoms of ICANS. Rule out other causes of ICANS symptoms. Monitor patients for signs or symptoms of ICANS for at least 4 weeks after infusion and treat promptly. Neurologic toxicity should be managed with supportive care and/or corticosteroids as needed.Parkinsonism: Of the 25 patients in the CARTITUDE-1 study experiencing any neurotoxicity, five male patients had neurologic toxicity with several signs and symptoms of parkinsonism, distinct from immune effector cell-associated neurotoxicity syndrome (ICANS). Neurologic toxicity with parkinsonism has been reported in other ongoing trials of ciltacabtagene autoleucel. Patients had parkinsonian and non-parkinsonian symptoms that included tremor, bradykinesia, involuntary movements, stereotypy, loss of spontaneous movements, masked facies, apathy, flat affect, fatigue, rigidity, psychomotor retardation, micrographia, dysgraphia, apraxia, lethargy, confusion, somnolence, loss of consciousness, delayed reflexes, hyperreflexia, memory loss, difficulty swallowing, bowel incontinence, falls, stooped posture, shuffling gait, muscle weakness and wasting, motor dysfunction, motor and sensory loss, akinetic mutism, and frontal lobe release signs. The median onset of parkinsonism in the 5 patients in CARTITUDE-1 was 43 days (range 15-108) from infusion of ciltacabtagene autoleucel.Monitor patients for signs and symptoms of parkinsonism that may be delayed in onset and managed with supportive care measures. There is limited efficacy information with medications used for the treatment of Parkinson’s disease, for the improvement or resolution of parkinsonism symptoms following CARVYKTI® treatment.Guillain-Barré Syndrome: A fatal outcome following Guillain-Barré Syndrome (GBS) has occurred in another ongoing study of ciltacabtagene autoleucel despite treatment with intravenous immunoglobulin (IVIG). Symptoms reported include those consistent with Miller-Fisher variant of GBS, encephalopathy, motor weakness, speech disturbances and polyradiculoneuritis.Monitor for GBS. Evaluate patients presenting with peripheral neuropathy for GBS. Consider treatment of GBS with supportive care measures and in conjunction with immunoglobulin and plasma exchange, depending on severity of GBS.Immune Mediated Myelitis: Grade 3 myelitis has occurred 25 days following treatment in another ongoing study. Symptoms reported included hypoesthesia of the lower extremities and the lower abdomen with impaired sphincter control. Symptoms improved with the use of corticosteroids and intravenous immunoglobulin. Myelitis was ongoing at the time of death from other cause.Peripheral Neuropathy: Six patients in CARTITUDE-1 developed peripheral neuropathy. These neuropathies presented as sensory, motor or sensorimotor neuropathies. Median time of onset of symptoms was 62 days (range 4-136 days), median duration of peripheral neuropathies was 256 days (range 2-465 days) including those with ongoing neuropathy. Patients who experienced peripheral neuropathy also experienced cranial nerve palsies or GBS in other ongoing trials of ciltacabtagene autoleucel. Monitor patients for signs and symptoms of peripheral neuropathies.Cranial Nerve Palsies: Three patients (3.1%) experienced cranial nerve palsies in CARTITUDE1. All three patients had 7th cranial nerve palsy; one patient had 5th cranial nerve palsy as well. Median time to onset was 26 days (range 21-101 days) following infusion of ciltacabtagene autoleucel. Occurrence of 3rd and 6th cranial nerve palsy, bilateral 7th cranial nerve palsy, worsening of cranial nerve palsy after improvement, and occurrence of peripheral neuropathy in patients with cranial nerve palsy have also been reported in ongoing trials of ciltacabtagene autoleucel. Monitor patients for signs and symptoms of cranial nerve palsies. Consider management with systemic corticosteroids, depending on the severity and progression of signs and symptoms.Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS): Fatal HLH occurred in one patient (1%), 99 days after ciltacabtagene autoleucel. The HLH event was preceded by prolonged CRS lasting 97 days. The manifestations of HLH/MAS include hypotension, hypoxia with diffuse alveolar damage, coagulopathy, cytopenia, and multi-organ dysfunction, including renal dysfunction.One patient with Grade 4 HLH/MAS developed fatal intracerebral and gastrointestinal hemorrhage in the setting of coagulopathy and thrombocytopenia 12 days after treatment in another ongoing study. Patients who develop HLH/MAS have an increased risk of severe bleeding. Monitor hematological parameters in patients with HLH/MAS and transfuse per institutional guidelines.HLH is a life-threatening condition with a high mortality rate if not recognized and treated early. Treatment of HLH/MAS should be administered per institutional standards.CARVYKTI® REMS: Because of the risk of CRS and neurologic toxicities, CARVYKTI® is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the CARVYKTI® REMS.Further information is available at https://www.carvyktirems.com/ or 1-844-672-0067.Prolonged and Recurrent Cytopenias: Patients may exhibit prolonged and recurrent cytopenias following lymphodepleting chemotherapy and CARVYKTI® infusion. One patient underwent autologous stem cell therapy for hematopoietic reconstitution due to prolonged thrombocytopenia.In CARTITUDE-1, 30% (29/97) of patients experienced prolonged Grade 3 or 4 neutropenia and 41% (40/97) of patients experienced prolonged Grade 3 or 4 thrombocytopenia that had not resolved by Day 30 following ciltacabtagene autoleucel infusion.Recurrent Grade 3 or 4 neutropenia, thrombocytopenia, lymphopenia and anemia were seen in 63% (61/97), 18% (17/97), 60% (58/97), and 37% (36/97) after recovery from initial Grade 3 or 4 cytopenia following infusion. After Day 60 following ciltacabtagene autoleucel infusion, 31%, 12% and 6% of patients had a recurrence of Grade 3 or higher lymphopenia, neutropenia and thrombocytopenia, respectively, after initial recovery of their Grade 3 or 4 cytopenia. Eighty-seven percent (84/97) of patients had one, two, or three or more recurrences of Grade 3 or 4 cytopenias after initial recovery of Grade 3 or 4 cytopenia. Six and 11 patients had Grade 3 or 4 neutropenia and thrombocytopenia, respectively, at the time of death.Monitor blood counts prior to and after CARVYKTI® infusion. Manage cytopenias with growth factors and blood product transfusion support according to local institutional guidelines.Infections: CARVYKTI® should not be administered to patients with active infection or inflammatory disorders. Severe, life-threatening or fatal infections occurred in patients after CARVYKTI® infusion.Infections (all grades) occurred in 57 (59%) patients. Grade 3 or 4 infections occurred in 23% (22/97) of patients; Grade 3 or 4 infections with an unspecified pathogen occurred in 17%, viral infections in 7%, bacterial infections in 1%, and fungal infections in 1% of patients. Overall, four patients had Grade 5 infections: lung abscess (n=1), sepsis (n=2) and pneumonia (n=1).Grade 5 infections reported in other studies include bronchopulmonary aspergillosis, pneumocystis jirovecii pneumonia, and CMV colitis (with HSV-1 hepatitis). Another patient developed mycotic aneurysm due to cerebral aspergillosis and died of subarachnoid hemorrhage.Monitor patients for signs and symptoms of infection before and after CARVYKTI® infusion and treat patients appropriately. Administer prophylactic, pre-emptive and/or therapeutic antimicrobials according to the standard institutional guidelines. Febrile neutropenia was observed in 10% of patients after ciltacabtagene autoleucel infusion, and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids and other supportive care, as medically indicated.In a randomized controlled study of relapsed or refractory multiple myeloma (CARTITUDE-4), patients treated with ciltacabtagene autoleucel had an increased rate of fatal COVID19 infections compared to the standard therapy arm. Counsel patients on the importance of prevention measures. Follow institutional guidelines for the vaccination and management of immunocompromised patients with COVID-19.Viral Reactivation: Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and death, can occur in patients with hypogammaglobulinemia. Perform screening for Cytomegalovirus (CMV), HBV, hepatitis C virus (HCV), and human immunodeficiency virus (HIV), or any other infectious agents if clinically indicated in accordance with clinical guidelines before collection of cells for manufacturing. Consider antiviral therapy to prevent viral reactivation per local institutional guidelines/clinical practice.Hypogammaglobulinemia was reported as an adverse event in 12% (12/97) of patients; laboratory IgG levels fell below 500 mg/dL after infusion in 92% (89/97) of patients. Monitor immunoglobulin levels after treatment with CARVYKTI® and administer IVIG for IgG <400 mg/dL. Manage per local institutional guidelines, including infection precautions and antibiotic or antiviral prophylaxis.Use of Live Vaccines: The safety of immunization with live viral vaccines during or following CARVYKTI® treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during CARVYKTI® treatment, and until immune recovery following treatment with CARVYKTI®.Hypersensitivity Reactions have occurred in 5% (5/97) of patients following ciltacabtagene autoleucel infusion. Serious hypersensitivity reactions, including anaphylaxis, may be due to the dimethyl sulfoxide (DMSO) in CARVYKTI®. Patients should be carefully monitored for 2 hours after infusion for signs and symptoms of severe reaction. Treat promptly and manage appropriately according to the severity of the hypersensitivity reaction.Secondary Malignancies: Patients may develop secondary malignancies. Monitor life-long for secondary malignancies. In the event that a secondary malignancy occurs, contact Janssen Biotech, Inc., at 1-800-526-7736 for reporting and to obtain instructions on collection of patient samples for testing of secondary malignancy of T cell origin.Effects on Ability to Drive and Use Machines: Due to the potential for neurologic events, including altered mental status, seizures, neurocognitive decline, or neuropathy, patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following CARVYKTI® infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery during this initial period, and in the event of new onset of any neurologic toxicities.ADVERSE REACTIONSThe most common non-laboratory adverse reactions (incidence greater than 20%) are pyrexia, cytokine release syndrome, hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue, infections of unspecified pathogen, cough, chills, diarrhea, nausea, encephalopathy, decreased appetite, upper respiratory tract infection, headache, tachycardia, dizziness, dyspnea, edema, viral infections, coagulopathy, constipation, and vomiting. The most common laboratory adverse reactions (incidence greater than or equal to 50%) include thrombocytopenia, neutropenia, anemia, aminotransferase elevation, and hypoalbuminemia.Please read full Prescribing Information, including Boxed Warning, for CARVYKTI®.TECVAYLI® IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONSCytokine Release Syndrome - TECVAYLI® can cause cytokine release syndrome (CRS), including life-threatening or fatal reactions. In the clinical trial, CRS occurred in 72% of patients who received TECVAYLI® at the recommended dose, with Grade 1 CRS occurring in 50% of patients, Grade 2 in 21%, and Grade 3 in 0.6%. Recurrent CRS occurred in 33% of patients. Most patients experienced CRS following step-up dose 1 (42%), step-up dose 2 (35%), or the initial treatment dose (24%). Less than 3% of patients developed first occurrence of CRS following subsequent doses of TECVAYLI®. The median time to onset of CRS was 2 (range: 1 to 6) days after the most recent dose with a median duration of 2 (range: 1 to 9) days. Clinical signs and symptoms of CRS included, but were not limited to, fever, hypoxia, chills, hypotension, sinus tachycardia, headache, and elevated liver enzymes (aspartate aminotransferase and alanine aminotransferase elevation).Initiate therapy according to TECVAYLI® step-up dosing schedule to reduce risk of CRS. Administer pretreatment medications to reduce risk of CRS and monitor patients following administration of TECVAYLI® accordingly. At the first sign of CRS, immediately evaluate patient for hospitalization. Administer supportive care based on severity and consider further management per current practice guidelines. Withhold or permanently discontinue TECVAYLI® based on severity.TECVAYLI® is available only through a restricted program under a REMS.Neurologic Toxicity including ICANS - TECVAYLI® can cause serious or life-threatening neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS).In the clinical trial, neurologic toxicity occurred in 57% of patients who received TECVAYLI® at the recommended dose, with Grade 3 or 4 neurologic toxicity occurring in 2.4% of patients. The most frequent neurologic toxicities were headache (25%), motor dysfunction (16%), sensory neuropathy (15%), and encephalopathy (13%). With longer follow-up, Grade 4 seizure and fatal Guillain-Barré syndrome (one patient each) occurred in patients who received TECVAYLI®.In the clinical trial, ICANS was reported in 6% of patients who received TECVAYLI® at the recommended dose. Recurrent ICANS occurred in 1.8% of patients. Most patients experienced ICANS following step-up dose 1 (1.2%), step-up dose 2 (0.6%), or the initial treatment dose (1.8%). Less than 3% of patients developed first occurrence of ICANS following subsequent doses of TECVAYLI®. The median time to onset of ICANS was 4 (range: 2 to 8) days after the most recent dose with a median duration of 3 (range: 1 to 20) days. The most frequent clinical manifestations of ICANS reported were confusional state and dysgraphia. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS.Monitor patients for signs and symptoms of neurologic toxicity during treatment. At the first sign of neurologic toxicity, including ICANS, immediately evaluate patient and provide supportive therapy based on severity. Withhold or permanently discontinue TECVAYLI® based on severity per recommendations and consider further management per current practice guidelines.Due to the potential for neurologic toxicity, patients are at risk of depressed level of consciousness. Advise patients to refrain from driving or operating heavy or potentially dangerous machinery during and for 48 hours after completion of TECVAYLI® step-up dosing schedule and in the event of new onset of any neurologic toxicity symptoms until neurologic toxicity resolves.TECVAYLI® is available only through a restricted program under a REMS.TECVAYLI® and TALVEY™ REMS - TECVAYLI® is available only through a restricted program under a REMS called the TECVAYLI® and TALVEY™ REMS because of the risks of CRS and neurologic toxicity, including ICANS.Hepatotoxicity - TECVAYLI® can cause hepatotoxicity, including fatalities. In patients who received TECVAYLI® at the recommended dose in the clinical trial, there was one fatal case of hepatic failure. Elevated aspartate aminotransferase (AST) occurred in 34% of patients, with Grade 3 or 4 elevations in 1.2%. Elevated alanine aminotransferase (ALT) occurred in 28% of patients, with Grade 3 or 4 elevations in 1.8%. Elevated total bilirubin occurred in 6% of patients with Grade 3 or 4 elevations in 0.6%. Liver enzyme elevation can occur with or without concurrent CRS.Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold TECVAYLI® or consider permanent discontinuation of TECVAYLI® based on severity.Infections - TECVAYLI® can cause severe, life-threatening, or fatal infections. In patients who received TECVAYLI® at the recommended dose in the clinical trial, serious infections, including opportunistic infections, occurred in 30% of patients, with Grade 3 or 4 infections in 35%, and fatal infections in 4.2%. Monitor patients for signs and symptoms of infection prior to and during treatment with TECVAYLI® and treat appropriately. Administer prophylactic antimicrobials according to guidelines. Withhold TECVAYLI® or consider permanent discontinuation of TECVAYLI® based on severity.Monitor immunoglobulin levels during treatment with TECVAYLI® and treat according to guidelines, including infection precautions and antibiotic or antiviral prophylaxis.Neutropenia - TECVAYLI® can cause neutropenia and febrile neutropenia. In patients who received TECVAYLI® at the recommended dose in the clinical trial, decreased neutrophils occurred in 84% of patients, with Grade 3 or 4 decreased neutrophils in 56%. Febrile neutropenia occurred in 3% of patients.Monitor complete blood cell counts at baseline and periodically during treatment and provide supportive care per local institutional guidelines. Monitor patients with neutropenia for signs of infection. Withhold TECVAYLI® based on severity.Hypersensitivity and Other Administration Reactions - TECVAYLI® can cause both systemic administration-related and local injection-site reactions. Systemic Reactions - In patients who received TECVAYLI® at the recommended dose in the clinical trial, 1.2% of patients experienced systemic-administration reactions, which included Grade 1 recurrent pyrexia and Grade 1 swollen tongue. Local Reactions - In patients who received TECVAYLI® at the recommended dose in the clinical trial, injection-site reactions occurred in 35% of patients, with Grade 1 injection-site reactions in 30% and Grade 2 in 4.8%. Withhold TECVAYLI® or consider permanent discontinuation of TECVAYLI® based on severity.Embryo-Fetal Toxicity - Based on its mechanism of action, TECVAYLI® may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with TECVAYLI® and for 5 months after the last dose.ADVERSE REACTIONSThe most common adverse reactions (≥20%) were pyrexia, CRS, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea. The most common Grade 3 to 4 laboratory abnormalities (≥20%) were decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin, and decreased platelets.Please read full Prescribing Information, including Boxed WARNING, for TECVAYLI®.TALVEY™ Important Safety InformationCONTRAINDICATIONS: NoneWARNINGS AND PRECAUTIONSCytokine Release Syndrome (CRS): TALVEY™ can cause cytokine release syndrome, including life-threatening or fatal reactions. In the clinical trial, CRS occurred in 76% of patients who received TALVEY™ at the recommended dosages, with Grade 1 CRS occurring in 57% of patients, Grade 2 in 17%, and Grade 3 in 1.5%. Recurrent CRS occurred in 30% of patients. Most events occurred following step-up dose 1 (29%), step-up dose 2 (44%), or the initial treatment dose for the weekly dosing schedule (30%) (N=186) and the third step-up dose for the biweekly dosing schedule (33%) (N=153). CRS occurred in 12% of patients treated with the first 0.8 mg/kg dose of the biweekly dosing schedule. The median time to onset of CRS was 27 (range: 0.1 to 167) hours from the last dose, and the median duration was 17 (range: 0 to 622) hours. Clinical signs and symptoms of CRS include but are not limited to pyrexia, hypotension, chills, hypoxia, headache and tachycardia. Potentially life-threatening complications of CRS may include cardiac dysfunction, acute respiratory distress syndrome, neurologic toxicity, renal and/or hepatic failure and disseminated intravascular coagulation (DIC).Initiate therapy with step-up dosing and administer pre-treatment medications (corticosteroids, antihistamine and antipyretics) prior to each dose of TALVEY™ in the step-up dosing schedule to reduce the risk of CRS. Monitor patients following administration accordingly. In patients who experience CRS, pre-treatment medications should be administered prior to the next TALVEY™ dose.Counsel patients to seek medical attention should signs or symptoms of CRS occur. At the first sign of CRS, immediately evaluate patient for hospitalization and institute treatment with supportive care based on severity and consider further management per current practice guidelines. Withhold TALVEY™ until CRS resolves or permanently discontinue based on severity.Neurologic Toxicity including ICANS: TALVEY™ can cause serious, life-threatening or fatal neurologic toxicity, including ICANS. In the clinical trial, neurologic toxicity including ICANS occurred in 55% of patients who received the recommended dosages, with Grade 3 or 4 neurologic toxicity occurring in 6% of patients. The most frequent neurologic toxicities were headache (20%), encephalopathy (15%), sensory neuropathy (14%), motor dysfunction (10%).ICANS was reported in 9% of 265 patients where ICANS was collected and who received the recommended dosages. Recurrent ICANS occurred in 3% of patients. Most patients experienced ICANS following step-up dose 1 (3%), step-up dose 2 (3%), step-up dose 3 of the biweekly dosing schedule (1.8%), or the initial treatment dose of the weekly dosing schedule (2.6%) (N=156) or the biweekly dosing schedule (3.7%) (N=109). The median time to onset of ICANS was 2.5 (range: 1 to 16) days after the most recent dose with a median duration of 2 (range: 1 to 22) days. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Clinical signs and symptoms of ICANS may include but are not limited to confusional state, depressed level of consciousness, disorientation, somnolence, lethargy and bradyphrenia.Monitor patients for signs and symptoms of neurologic toxicity during treatment. At the first sign of neurologic toxicity, including ICANS, immediately evaluate the patient and provide supportive care based on severity. Withhold or permanently discontinue TALVEY™ based on severity and consider further management per current practice guidelines (see Dosage and Administration [2.5] in the full Prescribing Information).Due to the potential for neurologic toxicity, patients receiving TALVEY™ are at risk of depressed level of consciousness. Advise patients to refrain from driving or operating heavy or potentially dangerous machinery during the step-up dosing schedule and for 48 hours after completion of the step-up dosing schedule and in the event of new onset of any neurological symptoms, until symptoms resolve.TECVAYLI® and TALVEY™ REMS: TALVEY™ is available only through a restricted program under a REMS called the TECVAYLI® and TALVEY™ REMS because of the risks of CRS and neurologic toxicity, including ICANS.Further information about the TECVAYLI® and TALVEY™ REMS program is available at www.TEC-TALREMS.com or by telephone at 1-855-810-8064.Oral Toxicity and Weight Loss: TALVEY™ can cause oral toxicities, including dysgeusia, dry mouth, dysphagia and stomatitis. In the clinical trial, 80% of patients had oral toxicity, with Grade 3 occurring in 2.1% of patients who received the recommended dosages. The most frequent oral toxicities were dysgeusia (49%), dry mouth (34%), dysphagia (23%) and ageusia (18%). The median time to onset of oral toxicity was 15 (range: 1 to 634) days, and the median time to resolution to baseline was 43 (1 to 530) days. Oral toxicity did not resolve to baseline in 65% of patients.TALVEY™ can cause weight loss. In the clinical trial, 62% of patients experienced weight loss, regardless of having an oral toxicity, including 29% of patients with Grade 2 (10% or greater) weight loss and 2.7% of patients with Grade 3 (20% or greater) weight loss. The median time to onset of Grade 2 or higher weight loss was 67 (range: 6 to 407) days, and the median time to resolution was 50 (range: 1 to 403) days. Weight loss did not resolve in 57% of patients who reported weight loss.Monitor patients for signs and symptoms of oral toxicity. Counsel patients to seek medical attention should signs or symptoms of oral toxicity occur and provide supportive care as per current clinical practice including consultation with a nutritionist. Monitor weight regularly during therapy. Evaluate clinically significant weight loss further. Withhold TALVEY™ or permanently discontinue based on severity.Infections: TALVEY™ can cause infections, including life-threatening or fatal infections. Serious infections occurred in 16% of patients, with fatal infections in 1.5% of patients. Grade 3 or 4 infections occurred in 17% of patients. The most common serious infections reported were bacterial infection (8%), which included sepsis, and COVID-19 (2.7%).Monitor patients for signs and symptoms of infection prior to and during treatment with TALVEY™ and treat appropriately. Administer prophylactic antimicrobials according to local guidelines. Withhold or permanently discontinue TALVEY™ as recommended based on severity.Cytopenias: TALVEY™ can cause cytopenias, including neutropenia and thrombocytopenia. In the clinical trial, Grade 3 or 4 decreased neutrophils occurred in 35% of patients, and Grade 3 or 4 decreased platelets occurred in 22% of patients who received TALVEY™. The median time to onset for Grade 3 or 4 neutropenia was 22 (range: 1 to 312) days, and the median time to resolution to Grade 2 or lower was 8 (range: 1 to 79) days. The median time to onset for Grade 3 or 4 thrombocytopenia was 12 (range: 2 to 183) days, and the median time to resolution to Grade 2 or lower was 10 (range: 1 to 64) days. Monitor complete blood counts during treatment and withhold TALVEY™ as recommended based on severity.Skin Toxicity: TALVEY™ can cause serious skin reactions, including rash, maculo-papular rash, erythema and erythematous rash. In the clinical trial, skin reactions occurred in 62% of patients, with Grade 3 skin reactions in 0.3%. The median time to onset was 25 (range: 1 to 630) days. The median time to improvement to Grade 1 or less was 33 days.Monitor for skin toxicity, including rash progression. Consider early intervention and treatment to manage skin toxicity. Withhold or permanently discontinue TALVEY™ based on severity.Hepatotoxicity: TALVEY™ can cause hepatoxicity. In the clinical trial, elevated ALT occurred in 33% of patients, with Grade 3 or 4 ALT elevation occurring in 2.7%; elevated AST occurred in 31% of patients, with Grade 3 or 4 AST elevation occurring in 3.3%. Grade 3 or 4 elevations of total bilirubin occurred in 0.3% of patients. Liver enzyme elevation can occur with or without concurrent CRS.Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold TALVEY™ or consider permanent discontinuation of TALVEY™ based on severity (see Dosage and Administration [2.5] in the full Prescribing Information).Embryo-Fetal Toxicity: Based on its mechanism of action, TALVEY™ may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with TALVEY™ and for 3 months after the last dose.Please read full Prescribing Information including Boxed Warning for TALVEY™.About the Janssen Pharmaceutical Companies of Johnson & JohnsonAt Janssen, we're creating a future where disease is a thing of the past. We're the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular, Metabolism & Retina; Immunology; Infectious Diseases & Vaccines; Neuroscience; Oncology; and Pulmonary Hypertension.Learn more at www.janssen.com. Follow us at @JanssenUS and @JanssenGlobal. Janssen Research & Development, LLC and Janssen Biotech, Inc. are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.†See the NCCN Guidelines for detailed recommendations, including other treatment options.Cautions Concerning Forward-Looking StatementsThis press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of CARVYKTI® (ciltacabtagene autoleucel), TECVAYLI® (teclistamab-cqyv), TALVEY™ (talquetamab-tgvs), DARZALEX® (daratumumab), DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj). The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections Janssen Research & Development, LLC, Janssen Biotech, Inc., any of the other Janssen Pharmaceutical Companies and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended January 1, 2023, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in Johnson & Johnson’s subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of the Janssen Pharmaceutical Companies nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.References1Rajkumar SV. Multiple myeloma: 2020 update on diagnosis, risk-stratification and management. Am J Hematol. 2020;95(5):548-5672020;95(5):548-567. http://www.ncbi.nlm.nih.gov/pubmed/322121782National Cancer Institute. Plasma Cell Neoplasms. 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