Human Normal Immunoglobulin (The Japan Blood Products Organization)

Real-World Evidence Study Strengthens the Body of Evidence Supporting ANX005 for Treatment of GBS ANX005 Phase 3 Population Was Matched 1:1 on Prespecified Criteria with Patients in International GBS Outcomes Study (IGOS) Matched Cohort Study Showed Early and Greater Benefits of ANX005 over IVIg or PE in Muscle Strength and Functional Outcomes Across Multiple Measurements Conference Call and Webcast Today at 8:30 a.m. ET BRISBANE, Calif., Dec. 16, 2024 (GLOBE NEWSWIRE) -- Annexon, Inc. (Nasdaq: ANNX), a biopharmaceutical company advancing a late-stage clinical platform of novel therapies for people living with devastating classical complement-mediated neuroinflammatory diseases of the body, brain, and eye, today announced positive topline results from a real-world evidence (RWE) study supporting ANX005 as a potential treatment for Guillain-Barré Syndrome (GBS). GBS is a rapid-onset and acute neuromuscular disease with no U.S. Food and Drug Administration (FDA)-approved treatments. ANX005, the most advanced targeted immunotherapy in development for GBS, is designed to rapidly block C1q and complement activity with a single dose to halt disease progression during the critical progressive phase of the disease. Working in collaboration, the IGOS investigators and Annexon established a cohort of 79 real-world patients from the IGOS global patient registry that was matched based on key prespecified prognostic factors to the cohort of 79 patients treated with ANX005 30 mg/kg from Annexon’s completed Phase 3 study conducted outside the United States. Patients in the ANX005 Phase 3 population had moderate to severe disease, and the matching level demonstrates that the Phase 3 population is represented within the global GBS patient spectrum captured in IGOS. Patients treated with ANX005 showed faster and greater improvement in muscle strength and disability compared to patients in the matched IGOS cohort treated with IVIg or PE. The comparison also showed that fewer patients treated with ANX005 required mechanical ventilation. Further, ANX005-treated patients were observed to spend less time on ventilation and less time in the intensive care unit (ICU). These findings indicate that ANX005 may decrease the overall burden of GBS care. “We’re highly encouraged by the growing body of evidence demonstrating consistent, robust effects of ANX005 treatment across the Phase 3 trial and in this real-world study of patients with GBS,” said Douglas Love, president and chief executive officer of Annexon. “We look forward to discussing these data and our overall regulatory package with regulators as we prepare for our planned U.S. Biologics License Application submission in the first half of 2025.” Hugh Willison, MBBS, PhD, professor emeritus of neurology, University of Glasgow and a member of the IGOS Steering Committee added: “In this analysis, patients treated with a single dose of ANX005 showed improved and more rapid benefit on muscle strength and disability over matched patients treated with multiple days of IVIg or PE. Recognizing the common role of complement biology in GBS pathogenesis, it’s reasonable to expect these results could translate well to a broad population of patients with GBS.” Key findings comparing ANX005 30 mg/kg to IVIg or PE: By week 1, patients treated with ANX005 showed more than a 10-point improvement in muscle strength over patients treated with IVIg or PE, a clinically meaningful benefit as measured by Medical Research Council (MRC) sumscore and an indicator for future recovery potential1 (p < 0.0001) Patients treated with ANX005 were approximately twice as likely to be in a better state of health than patients on IVIg or PE on the GBS-Disability Scale (GBS-DS) at multiple timepoints throughout the study, including at week 8, the primary endpoint for the Phase 3 trial (p = 0.0459) Approximately half the number of patients treated with ANX005 (n=15 of 79) required mechanical ventilation compared with patients treated with IVIg or PE (n=32 of 79) (p = 0.022) ANX005-treated patients were observed to spend fewer days on mechanical ventilation and fewer days in the ICU (median of 12 fewer days for each measure, p = n.s.*) “GBS is a traumatizing disease that can affect anyone, anywhere, at any time, resulting in nerve damage, severe weakness and acute paralysis,” said Lisa Butler, executive director, GBS/CIDP Foundation International. “These new data from the ANX005 real-world study support the value of ANX005 as a potential novel targeted therapy for GBS. After decades with limited treatment options, none of which are FDA-approved, the GBS community deserves a future where patients can be hopeful for a quicker recovery and better outcomes.” Conference Call and Webcast InformationAnnexon management will hold a conference call and webcast today at 8:30 a.m. ET to discuss topline results from its real-world evidence (RWE) study in GBS. The dial-in number for the conference call is 1-877-407-0784 (U.S./Canada) or 1-201-689-8560 (international). The conference ID for all callers is 13750635. The live webcast and replay may be accessed by visiting Annexon’s website at https://ir.annexonbio.com/events-and-presentations/events. Call me™: Click here. Participants can use guest dial-in numbers above and be answered by an operator or they can click the Call me™ link for instant telephone access to the event (dial-out). The Call me™ link will be made active 15 minutes prior to scheduled start time. About the Real-World Evidence Study Comparing ANX005 Treatment to IGOS Matched CohortWorking in collaboration, the IGOS investigators and Annexon conducted the RWE study. The RWE study applied a well-accepted statistical method of propensity score matching to establish 1:1 cohorts of patients matched on key prespecified prognostic factors of disease severity (muscle strength and GBS disability score measured at the time of hospitalization, prior to treatment). The same analytical and statistical approaches used to measure efficacy in the Phase 3 trial were applied to assess treatment effect in the matched populations (n=79 in each cohort). IGOS is a global, prospective, observational, multicenter cohort study that enrolled 2,000 patients who were followed for one to three years. Consistent with global standards of care (SoC), patients in the IGOS registry were treated with IVIg or PE. Published literature has demonstrated that more severe patients experience less benefit from IVIg or PE, further highlighting the unmet need in this patient population.2, 3, 4, 5 About ANX005Annexon’s lead investigational therapy, ANX005, is a first-of-its kind selective, targeted and rapid-acting agent designed to reduce inflammation and nerve damage by stopping C1q activity in the peripheral and central nervous systems. In GBS, ANX005 is designed to seek out C1q and prevent its binding to targets on peripheral nerves. ANX005 is administered intravenously and has been observed to act almost immediately in blocking C1q function. The aim of an effective treatment in GBS is to rapidly stop the autoimmune damage on nerve cells, allowing patients to regain muscle strength sooner and to regain independence and return to pre-illness activities. ANX005 has received both Fast Track and Orphan Drug designations from the U.S. Food and Drug Administration as well as orphan drug designation from the European Medicines Agency for the treatment of GBS. About the ANX005 Phase 3 Trial Positive data from a previously reported Phase 3 study demonstrated statistically significant effects of 30mg/kg ANX005 treatment over placebo on multiple measures of GBS, including on the primary endpoint GBS-DS. Patients treated with ANX005 demonstrated a higher likelihood of being in a better state of health at week 1 on the GBS-DS, a benefit that was observed across the 26-week study period. Early, robust and durable treatment effects were observed, which resulted in expedited recovery and reduced days on mechanical ventilation, allowing patients to walk approximately one month earlier. ANX005 was generally well-tolerated with a safety profile similar to placebo. About Guillain-Barré Syndrome (GBS)GBS is a severe disease resulting from an acute autoantibody and classical complement-mediated attack on peripheral nerves that generally occurs post-infection in otherwise healthy persons. It is an acute, rapidly progressive neurological disease with a narrow timeframe for therapeutic intervention. GBS results in the hospitalization of more than 22,000 people annually in the U.S. and Europe. The peripheral nerve damage progresses rapidly, causing acute neuromuscular paralysis that can lead to significant morbidity, disability and mortality. Currently, there are no approved treatments for GBS in the United States. The long-term disease burden associated with GBS has led to a multi-billion-dollar annual economic cost to the U.S. healthcare system alone. About AnnexonAnnexon Biosciences (Nasdaq: ANNX) is harnessing therapeutics against classical complement-driven neuroinflammation to advance potentially first-in-kind treatments for millions of people living with serious neuroinflammatory diseases of the body, brain and eye. Our novel scientific approach focuses on C1q, the initiating molecule of the classical complement cascade, which can inappropriately lead to severe tissue damage and loss. By targeting C1q, our immunotherapies are designed to stop neuroinflammatory diseases where they start. Our pipeline spans three diverse therapeutic areas – autoimmune, neurodegenerative and ophthalmic diseases – and includes targeted investigational drug candidates designed to address the unmet needs of over 8 million people worldwide. Annexon’s mission is to deliver game-changing therapies to patients so that they can live their best lives. To learn more visit annexonbio.com. *n.s. = not significant References 1 Walgaard, et al., 2011. Early recognition of poor prognosis in Guillain-Barré syndrome. Neurology 76:968. 2 The French Cooperative Group on Plasma Exchange in Guillain–Barré Syndrome. Plasma exchange in Guillain–Barré syndrome. Ann Neurol. 1987;22(6):753-761. 3 Hughes RAC, Swan AV, van Doorn PA. Intravenous immunoglobulin for Guillain‐Barré syndrome. Cochrane Database Syst Rev. 2014;(9):CD002063. 4 Van der Meché FGA, Schmitz PIM. A randomized trial comparing intravenous immune globulin and plasma exchange in Guillain–Barré syndrome. N Engl J Med. 1992;326(17):1123-1129. 5 Walgaard C, Lingsma HF, Ruts L, et al. Second intravenous immunoglobulin dose in patients with Guillain-Barré syndrome with poor prognosis (SID-GBS): a double-blind, randomized, placebo-controlled trial. Lancet Neurol. 2021;20(4):275-283. Forward Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. In some cases, you can identify forward-looking statements by terminology such as “aim,” “anticipate,” “assume,” “believe,” “contemplate,” “continue,” “could,” “design,” “due,” “estimate,” “expect,” “goal,” “intend,” “may,” “objective,” “plan,” “positioned,” “potential,” “predict,” “seek,” “should,” “suggest,” “target,” “on track,” “will,” “would” and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology. All statements other than statements of historical facts contained in this press release are forward-looking statements. These forward-looking statements include, but are not limited to, statements about: ability of ANX005 to stop C1q activity; ability to bring ANX005 to patients worldwide as soon as possible; the clinical and regulatory status of ANX005; the overall treatment potential of ANX005; the ability to translate the results of the RWE study to a broad population of GBS patients; the timing and outcomes of ongoing and future interactions with regulatory bodies, including the FDA; the adequacy and sufficiency of the RWE data to support marketing application; the anticipated timeline of our planned Biologics License Application (BLA) submission in the first half of 2025; the potential therapeutic benefit of ANX005 or any other product candidates on GBS, or other autoimmune, neurodegenerative and ophthalmic diseases; potential benefit of ANX005, if approved, compared to IVIg/plasma exchange or other existing therapies; and market size for GBS and other therapeutic areas of interest for Annexon. Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause actual results and events to differ materially from those anticipated, including, but not limited to, risks and uncertainties related to: the potential that FDA or EU regulators may not find the data from the RWE study sufficient for filing of a BLA; the potential that FDA and comparable foreign regulatory authorities may require additional information or studies prior to the approval of ANX005; the potential that regulatory authorities may not find the results of the ANX005 trial conducted outside the United States translate to a broad population of GBS patients; the potential for any final clinical trial results to differ from preliminary or topline results; the company’s history of net operating losses; the company’s ability to obtain necessary capital to fund its clinical programs; the early stages of clinical development of the company’s product candidates; the effects of public health crises on the company’s clinical programs and business operations; the company’s ability to obtain regulatory approval of and successfully commercialize its product candidates; any undesirable side effects or other properties of the company’s product candidates; the company’s reliance on third-party suppliers and manufacturers; the outcomes of any future collaboration agreements; and the company’s ability to adequately maintain intellectual property rights for its product candidates. These and other risks are described in greater detail under the section titled “Risk Factors” contained in the company’s Annual Report on Form 10-K and Quarterly Reports on Form 10-Q and the company’s other filings with the SEC. Any forward-looking statements that the company makes in this press release are made pursuant to the Private Securities Litigation Reform Act of 1995, as amended, and speak only as of the date of this press release. Except as required by law, the company undertakes no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise. Investor Contact:Joyce AllaireLifeSci Advisors, LLCjallaire@lifesciadvisors.com Media Contact:Sheryl SeapyReal Chemistry949-903-4750sseapy@realchemistry.com

89 percent of patients evaluable for MRD assessment were MRD negative, with the majority reaching MRD negativity in less than 2 months Results add to the overall survival (OS) benefits recently presented, as the first and only cell therapy to significantly extend OS versus standard therapies in multiple myeloma SAN DIEGO, Dec. 9, 2024 /PRNewswire/ -- Johnson & Johnson (NYSE:JNJ) announced today new results from the Phase 3 CARTITUDE-4 study that show a single infusion of CARVYKTI® (ciltacabtagene autoleucel; cilta-cel) significantly increased minimal residual disease (MRD) negativity rates (10-5) in patients with relapsed or refractory multiple myeloma (RRMM) who were lenalidomide-refractory and had received one to three prior lines of therapy, including a proteasome inhibitor (PI), compared to standard therapies of pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd).1 MRD is a prognostic marker of prolonged survival outcomes for patients with multiple myeloma. These results add to the overall survival (OS) benefits recently presented at the International Myeloma Society meeting earlier this year, as the first and only cell therapy to significantly extend OS versus standard therapies for patients with multiple myeloma.1 Findings were featured in an oral presentation at the 2024 American Society of Hematology (ASH) Annual Meeting (Abstract #1032).1 "CARVYKTI has established its significant impact on overall survival and improved progression-free survival compared to standard therapies," said Rakesh Popat, M.D., University College London Hospitals, NHS Foundation Trust, London, UK, and lead study investigator.* "The MRD negativity results demonstrate deep responses compared to standard therapies for people living with multiple myeloma and further underscore the benefit of CARVYKTI, administered as a single infusion as early as second line." The Phase 3 CARTITUDE-4 study evaluated CARVYKTI® compared to standard therapies of PVd or DPd for the treatment of patients with RRMM as early as after one prior line of therapy.1 Patients who received one to three prior lines of therapy, including a PI and immunomodulatory agent (IMiD), and were lenalidomide-refractory, were randomized (CARVYKTI®, n=208, standard therapies, n=211).1 At a median follow-up of almost three years (34 months), MRD-negativity rates for evaluable patients were more than double in those treated with CARVYKTI® versus standard therapies (89 percent, 38 percent; P<0.0001).1 At 2.5 years, sustained (12 months or more), MRD-negative complete response or better in evaluable patients treated with CARVYKTI® was five-fold higher than that of standard therapies (52 percent, 10 percent; P<0.0001). A post-hoc comparison between CARTITUDE-4 and CARTITUDE-1 was also presented, comparing earlier treatment (1-3 versus 3+ prior lines of therapy) demonstrating higher rates of MRD negativity, progression-free survival (PFS) and OS rates when CARVYKTI® is used earlier in treatment. "We are thrilled to present the latest MRD negativity results from the CARTITUDE-4 study showing that CARVYKTI, the first and only cell therapy approved for the treatment of patients with multiple myeloma as early as second line, shows profound long-term remission rates, including progression-free survival and overall survival benefits," said Jordan Schecter, M.D., Vice President, Disease Area Leader, Multiple Myeloma, Johnson & Johnson Innovative Medicine. "It is also increasingly clear that reaching MRD negativity is a key goal with CAR-T therapy in myeloma, and we see that MRD rates were higher in this analysis with earlier treatment." Additional data on patient reported outcomes (PROs) and time to worsening (TTW) of symptoms with CARVYKTI® will also be presented at ASH 2024 as a poster presentation (Abstract #2002).2 Based on the Multiple Myeloma Symptom and Impact Questionnaire (MySlm-Q) system and impact domain scores, patients treated with CARVYKTI® reported significantly longer TTW of symptoms compared to standard therapies.2 At three-year follow up, 83 percent of patients treated with CARVYKTI® had not experienced worsening of functional impacts, compared to 69 percent in the standard therapies arm.2 About CARTITUDE-4 CARTITUDE-4 (NCT04181827) is the first randomized Phase 3 study evaluating the efficacy and safety of CARVYKTI®. The study compares CARVYKTI® with standard of care treatments PVd or DPd in adult patients with relapsed and lenalidomide-refractory multiple myeloma who received one to three prior lines of therapy. The primary endpoint of the study is PFS; safety, OS, MRD negativity rate and overall response rate are secondary endpoints. About CARVYKTI® (ciltacabtagene autoleucel; cilta-cel) CARVYKTI® is a BCMA-directed, genetically modified autologous T-cell immunotherapy that 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. 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. In April 2024, CARVYKTI® was approved as the first and only cell therapy in the U.S. for treatment of adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy including a proteasome inhibitor, an immunomodulatory agent, and who are refractory to lenalidomide. In April 2024, the European Medicines Agency (EMA) approved a Type II variation for CARVYKTI® for the treatment of adults with relapsed and refractory multiple myeloma who have received at least one prior therapy, including an immunomodulatory agent and a proteasome inhibitor, have demonstrated disease progression on the last therapy, and are refractory to lenalidomide. In December 2017, Janssen Biotech, Inc., a Johnson & Johnson company, entered into an exclusive worldwide license and collaboration agreement with Legend Biotech USA, Inc. to develop and commercialize CARVYKTI®. For more information, visit . About Multiple Myeloma Multiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.3 In multiple myeloma, these plasma cells proliferate and spread rapidly and replace normal cells in the bone marrow with tumors.4 Multiple myeloma is the third most common blood cancer worldwide and remains an incurable disease.5 In 2024, it was estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 people would die from the disease.6 People living with multiple myeloma have a 5-year survival rate of 59.8 percent.7 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.8,9 CARVYKTI® IMPORTANT SAFETY INFORMATION INDICATIONS AND USAGE CARVYKTI® (ciltacabtagene autoleucel) is a B-cell maturation antigen (BCMA)-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory multiple myeloma, who have received at least 1 prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent, and are refractory to lenalidomide. IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Increased early mortality - In CARTITUDE-4, a (1:1) randomized controlled trial, there was a numerically higher percentage of early deaths in patients randomized to the CARVYKTI® treatment arm compared to the control arm. Among patients with deaths occurring within the first 10 months from randomization, a greater proportion (29/208; 14%) occurred in the CARVYKTI® arm compared to (25/211; 12%) in the control arm. Of the 29 deaths that occurred in the CARVYKTI® arm within the first 10 months of randomization, 10 deaths occurred prior to CARVYKTI® infusion, and 19 deaths occurred after CARVYKTI® infusion. Of the 10 deaths that occurred prior to CARVYKTI® infusion, all occurred due to disease progression, and none occurred due to adverse events. Of the 19 deaths that occurred after CARVYKTI® infusion, 3 occurred due to disease progression, and 16 occurred due to adverse events. The most common adverse events were due to infection (n=12). Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred following treatment with CARVYKTI®. Among patients receiving CARVYKTI® for RRMM in the CARTITUDE-1 & 4 studies (N=285), CRS occurred in 84% (238/285), including ≥Grade 3 CRS (ASCT 2019) in 4% (11/285) of patients. Median time to onset of CRS, any grade, was 7 days (range: 1 to 23 days). CRS resolved in 82% with a median duration of 4 days (range: 1 to 97 days). The most common manifestations of CRS in all patients combined (≥10%) included fever (84%), hypotension (29%) and aspartate aminotransferase increased (11%). Serious events that may be associated with CRS include pyrexia, hemophagocytic lymphohistiocytosis, respiratory failure, disseminated intravascular coagulation, capillary leak syndrome, and supraventricular and ventricular tachycardia. CRS occurred in 78% of patients in CARTITUDE-4 (3% Grade 3 to 4) and in 95% of patients in CARTITUDE-1 (4% Grade 3 to 4). 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. Ensure that a minimum of two doses of tocilizumab are available prior to infusion of CARVYKTI®. Of the 285 patients who received CARVYKTI® in clinical trials, 53% (150/285) patients received tocilizumab; 35% (100/285) received a single dose, while 18% (50/285) received more than 1 dose of tocilizumab. Overall, 14% (39/285) of patients received at least one dose of corticosteroids for treatment of CRS. 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, GBS, 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. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies for RRMM, one or more neurologic toxicities occurred in 24% (69/285), including ≥Grade 3 cases in 7% (19/285) of patients. Median time to onset was 10 days (range: 1 to 101) with 63/69 (91%) of cases developing by 30 days. Neurologic toxicities resolved in 72% (50/69) of patients with a median duration to resolution of 23 days (range: 1 to 544). Of patients developing neurotoxicity, 96% (66/69) also developed CRS. Subtypes of neurologic toxicities included ICANS in 13%, peripheral neuropathy in 7%, cranial nerve palsy in 7%, parkinsonism in 3%, and immune mediated myelitis in 0.4% of the patients. Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS): Patients receiving CARVYKTI® 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. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, ICANS occurred in 13% (36/285), including Grade ≥3 in 2% (6/285) of the patients. Median time to onset of ICANS was 8 days (range: 1 to 28 days). ICANS resolved in 30 of 36 (83%) of patients with a median time to resolution of 3 days (range: 1 to 143 days). Median duration of ICANS was 6 days (range: 1 to 1229 days) in all patients including those with ongoing neurologic events at the time of death or data cut off. Of patients with ICANS 97% (35/36) had CRS. The onset of ICANS occurred during CRS in 69% of patients, before and after the onset of CRS in 14% of patients respectively. Immune Effector Cell-associated Neurotoxicity Syndrome occurred in 7% of patients in CARTITUDE-4 (0.5% Grade 3) and in 23% of patients in CARTITUDE-1 (3% Grade 3). The most frequent ≥2% manifestations of ICANS included encephalopathy (12%), aphasia (4%), headache (3%), motor dysfunction (3%), ataxia (2%) and sleep disorder (2%). 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: Neurologic toxicity with parkinsonism has been reported in clinical trials of CARVYKTI®. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, parkinsonism occurred in 3% (8/285), including Grade ≥ 3 in 2% (5/285) of the patients. Median time to onset of parkinsonism was 56 days (range: 14 to 914 days). Parkinsonism resolved in 1 of 8 (13%) of patients with a median time to resolution of 523 days. Median duration of parkinsonism was 243.5 days (range: 62 to 720 days) in all patients including those with ongoing neurologic events at the time of death or data cut off. The onset of parkinsonism occurred after CRS for all patients and after ICANS for 6 patients. Parkinsonism occurred in 1% of patients in CARTITUDE-4 (no Grade 3 to 4) and in 6% of patients in CARTITUDE-1 (4% Grade 3 to 4). Manifestations of parkinsonism included movement disorders, cognitive impairment, and personality changes. 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 GBS occurred following treatment with CARVYKTI® despite treatment with intravenous immunoglobulins. 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 immunoglobulins and plasma exchange, depending on severity of GBS. Immune mediated myelitis: Grade 3 myelitis occurred 25 days following treatment with CARVYKTI® in CARTITUDE-4 in a patient who received CARVYKTI® as subsequent therapy. 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 immune globulin. Myelitis was ongoing at the time of death from other cause. Peripheral neuropathy occurred following treatment with CARVYKTI®. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, peripheral neuropathy occurred in 7% (21/285), including Grade ≥3 in 1% (3/285) of the patients. Median time to onset of peripheral neuropathy was 57 days (range: 1 to 914 days). Peripheral neuropathy resolved in 11 of 21 (52%) of patients with a median time to resolution of 58 days (range: 1 to 215 days). Median duration of peripheral neuropathy was 149.5 days (range: 1 to 692 days) in all patients including those with ongoing neurologic events at the time of death or data cut off. Peripheral neuropathies occurred in 7% of patients in CARTITUDE-4 (0.5% Grade 3 to 4) and in 7% of patients in CARTITUDE-1 (2% Grade 3 to 4). Monitor patients for signs and symptoms of peripheral neuropathies. Patients who experience peripheral neuropathy may also experience cranial nerve palsies or GBS. Cranial nerve palsies occurred following treatment with CARVYKTI®. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, cranial nerve palsies occurred in 7% (19/285), including Grade ≥3 in 1% (1/285) of the patients. Median time to onset of cranial nerve palsies was 21 days (range: 17 to 101 days). Cranial nerve palsies resolved in 17 of 19 (89%) of patients with a median time to resolution of 66 days (range: 1 to 209 days). Median duration of cranial nerve palsies was 70 days (range: 1 to 262 days) in all patients including those with ongoing neurologic events at the time of death or data cut off. Cranial nerve palsies occurred in 9% of patients in CARTITUDE-4 (1% Grade 3 to 4) and in 3% of patients in CARTITUDE-1 (1% Grade 3 to 4). The most frequent cranial nerve affected was the 7th cranial nerve. Additionally, cranial nerves III, V, and VI have been reported to be affected. 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): Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, HLH/MAS occurred in 1% (3/285) of patients. All events of HLH/MAS had onset within 99 days of receiving CARVYKTI®, with a median onset of 10 days (range: 8 to 99 days) and all occurred in the setting of ongoing or worsening CRS. The manifestations of HLH/MAS included hyperferritinemia, hypotension, hypoxia with diffuse alveolar damage, coagulopathy and hemorrhage, cytopenia and multi-organ dysfunction, including renal dysfunction and respiratory failure. Patients who develop HLH/MAS have an increased risk of severe bleeding. Monitor hematologic parameters in patients with HLH/MAS and transfuse per institutional guidelines. Fatal cases of HLH/MAS occurred following treatment with CARVYKTI®. 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 or 1-844-672-0067. Prolonged and Recurrent Cytopenias: Patients may exhibit prolonged and recurrent cytopenias following lymphodepleting chemotherapy and CARVYKTI® infusion. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, Grade 3 or higher cytopenias not resolved by day 30 following CARVYKTI® infusion occurred in 62% (176/285) of the patients and included thrombocytopenia 33% (94/285), neutropenia 27% (76/285), lymphopenia 24% (67/285) and anemia 2% (6/285). After Day 60 following CARVYKTI® infusion 22%, 20%, 5%, and 6% of patients had a recurrence of Grade 3 or 4 lymphopenia, neutropenia, thrombocytopenia, and anemia respectively, after initial recovery of their Grade 3 or 4 cytopenia. Seventy-seven percent (219/285) 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. Sixteen and 25 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. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, infections occurred in 57% (163/285), including ≥Grade 3 in 24% (69/285) of patients. Grade 3 or 4 infections with an unspecified pathogen occurred in 12%, viral infections in 6%, bacterial infections in 5%, and fungal infections in 1% of patients. Overall, 5% (13/285) of patients had Grade 5 infections, 2.5% of which were due to COVID-19. Patients treated with CARVYKTI® had an increased rate of fatal COVID-19 infections compared to the standard therapy arm. 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 5% of patients after CARVYKTI® 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. 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: can occur in patients receiving treatment with CARVYKTI®. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, hypogammaglobulinemia adverse event was reported in 36% (102/285) of patients; laboratory IgG levels fell below 500mg/dl after infusion in 93% (265/285) of patients. Hypogammaglobulinemia either as an adverse reaction or laboratory IgG level below 500mg/dl, after infusion occurred in 94% (267/285) of patients treated. Fifty six percent (161/285) of patients received intravenous immunoglobulin (IVIG) post CARVYKTI® for either an adverse reaction or prophylaxis. 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 occurred following treatment with CARVYKTI®. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, hypersensitivity reactions occurred in 5% (13/285), all of which were ≤Grade 2. Manifestations of hypersensitivity reactions included flushing, chest discomfort, tachycardia, wheezing, tremor, burning sensation, non-cardiac chest pain, and pyrexia. 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 patients appropriately according to the severity of the hypersensitivity reaction. Secondary Malignancies: Patients treated with CARVYKTI® may develop secondary malignancies. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, myeloid neoplasms occurred in 5% (13/285) of patients (9 cases of myelodysplastic syndrome, 3 cases of acute myeloid leukemia, and 1 case of myelodysplastic syndrome followed by acute myeloid leukemia). The median time to onset of myeloid neoplasms was 447 days (range: 56 to 870 days) after treatment with CARVYKTI®. Ten of these 13 patients died following the development of myeloid neoplasms; 2 of the 13 cases of myeloid neoplasm occurred after initiation of subsequent antimyeloma therapy. Cases of myelodysplastic syndrome and acute myeloid leukemia have also been reported in the post marketing setting. T-cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies, including CARVYKTI®. Mature T-cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusions, and may include fatal outcomes. 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. 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 receiving CARVYKTI® 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 REACTIONS The most common nonlaboratory adverse reactions (incidence greater than 20%) are pyrexia, cytokine release syndrome, hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue, infections-pathogen unspecified, 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 Grade 3 or 4 laboratory adverse reactions (incidence greater than or equal to 50%) include lymphopenia, neutropenia, white blood cell decreased, thrombocytopenia, and anemia. Please read full Prescribing Information, including Boxed Warning, for CARVYKTI®. About Johnson & Johnson At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity. Learn more at or at . Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC, Janssen Biotech, Inc., and Janssen Global Services, LLC are Johnson & Johnson companies. Cautions Concerning Forward-Looking Statements This 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; cilta-cel). 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 of Janssen Research & Development, LLC, Janssen Biotech, Inc., Janssen Global Services, LLC 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 December 31, 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 , or on request from Johnson & Johnson. None of Janssen Research & Development, LLC, Janssen Biotech, Inc., Janssen Global Services, LLC nor Johnson & Johnson undertake to update any forward-looking statement as a result of new information or future events or developments. * Dr Rakesh Popat, University College London Hospitals, NHS Foundation Trust, London, UK, has provided consulting, advisory, and speaking services to Johnson & Johnson; he has not been paid for any media work. 1 Popat R, et al. Ciltacabtagene Autoleucel (Cilta-cel) vs Standard of Care (SoC) in Patients With Lenalidomide (Len)-Refractory Multiple Myeloma (MM) After 1–3 Lines of Therapy: Minimal Residual Disease (MRD) Negativity in the Phase 3 CARTITUDE-4 Trial. American Society of Hematology 2024 Annual Meeting. December 2024. 2 Bar N, et al. Long-Term Benefits in Patient-Reported Outcomes and Time to Next Anti-Myeloma Therapy of Ciltacabtagene autoleucel (Cilta-cel) versus Standard of Care for Patients with Lenalidomide-Refractory Multiple Myeloma: Results from the Phase 3 CARTITUDE-4 Clinical Trial. American Society of Hematology 2024 Annual Meeting. December 2024. 3 Rajkumar SV. Multiple myeloma: 2020 update on diagnosis, risk-stratification and management. Am J Hematol. 2020;95(5):548-567. 4 National Cancer Institute. Plasma Cell Neoplasms. . Accessed December 2024. 5 City of Hope. Multiple Myeloma: Causes, Symptoms & Treatments. . Accessed December 2024. 6 American Cancer Society. Key Statistics About Multiple Myeloma. . Accessed December 2024. 7 SEER Explorer: An interactive website for SEER cancer statistics [Internet]. Surveillance Research Program, National Cancer Institute. . Accessed December 2024. 8 American Cancer Society. What is Multiple Myeloma? . Accessed December 2024. 9 American Cancer Society. Multiple Myeloma Early Detection, Diagnosis, and Staging. . Accessed December 2024. SOURCE Johnson & Johnson WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED