Tachycardia, Sinus

Favorable Findings from the Longest Public Clinical Study in CIDP Support HYQVIA as an Effective Long-Term Treatment Option for Maintaining Stable Disease Course in CIDP ADVANCE Clinical Program Reflects Takeda’s Commitment to Continued Research on the Role of Immunoglobulin (IG) Therapy for Patients with Rare Neuroimmunological Disorders OSAKA, Japan & CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Takeda (TSE:4502/NYSE:TAK) today announced data from the Phase 3 ADVANCE-CIDP 3 clinical trial, a long-term extension study evaluating the safety and efficacy of HYQVIA® [Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase] in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Results showed favorable long-term safety and tolerability of HYQVIA, and a low relapse rate, supporting its use as maintenance treatment for CIDP. These findings will be presented in a poster session on Sunday, June 23, 2024 at the Peripheral Nerve Society (PNS) Annual Meeting in Montreal, Canada. HYQVIA is the first and only facilitated subcutaneous immunoglobulin (fSCIG) for CIDP, approved earlier this year by the U.S. Food and Drug Association (FDA) as maintenance therapy in adults with CIDP and by the European Commission for patients of all ages with CIDP post-stabilization with intravenous immunoglobulin (IVIG). HYQVIA’s hyaluronidase component facilitates the dispersion and absorption of large immunoglobulin (IG) volumes in the subcutaneous space between the skin and the muscle. This allows high-volume IG administration (equivalent to volumes administered intravenously) into the subcutaneous tissue over a short time. As a result, HYQVIA can be infused up to once monthly (every two, three or four weeks). HYQVIA can be self-administered after appropriate patient or caregiver training or administered by a healthcare professional in a medical office, infusion center or at a patient’s home.1 “The long-term data from the ADVANCE-CIDP 3 clinical trial allow us to further characterize the safety, efficacy and tolerability pro HYQVIA and reinforces its role as a long-term, up-to once monthly maintenance treatment for this complex, chronic condition,” said Kristina Allikmets, senior vice president and head of Research & Development for Takeda’s Plasma-Derived Therapies Business Unit. “These results reflect our continued commitment to bringing the benefits of our differentiated immunoglobulin therapies to patients with neuroimmunological disorders, and providing a range of effective treatment options that address the individual needs of a broad range of patients.” The ADVANCE-CIDP 3 clinical trial is the longest extension study ever performed within context of a clinical trial in CIDP to date. The study, which enrolled 85 patients from the ADVANCE-CIDP 1 clinical trial, evaluated the safety, tolerability and immunogenicity of HYQVIA. The primary outcome measure was safety/tolerability and immunogenicity. The median duration of HYQVIA treatment was 33 months (0 to 77 months) with a cumulative overall follow-up time of 220 patient years. The findings were consistent with the known safety and tolerability pro HYQVIA and no new safety concerns were observed.2 Key findings showed: The median monthly dose of HYQVIA across all patients was 64 (28.0 to 200.0) g/4 weeks. The mean infusion duration per dose of HYQVIA was 135.5 minutes with 88.2% of doses administered every 4 weeks and 92.3% of doses administered across two infusion sites. HYQVIA was well tolerated among the 3487 infusions administered; 3 (0.1%) infusions had a reduced infusion rate, were interrupted or stopped due to intolerability. Overall, adverse events (AEs) were reported in 89.4% of patients. AEs related to HYQVIA were reported in 60% of patients. Most AEs were mild or moderate and self-limiting, and consistent with the established safety pro HYQVIA. The most common AEs per infusion (≥0.02 events per infusion) were headache, infusion site erythema, pyrexia, nausea, erythema, infusion site pruritis, fatigue and infusion site pain. Serious AEs possibly related to HYQVIA occurred in three patients (one event each): infection at the infusion site, exacerbation of migraine and fibromyalgia after infusion, and exacerbation of heart failure that resolved following treatment. HYQVIA maintained stable disease course in patients with CIDP. Thirteen percent of patients with data available experienced a relapse during the entire observation period with an annualized relapse rate of 4.5%. “Results of the ADVANCE-CIDP 3 study help provide additional confidence to those living with CIDP and their healthcare providers regarding the potential for extended maintenance of their condition with a facilitated subcutaneous immunoglobulin,” said Dr. Robert Hadden, MD, Consultant Neurologist, Neurology Department, King’s College Hospital, London, UK and Department of Basic & Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK and ADVANCE-CIDP 3 presenting author. “This treatment allows the convenience of potential self-treatment at home, typically only once every four weeks.” CIDP is an acquired, immune-mediated condition affecting the peripheral nervous system that is characterized by progressive, symmetric weakness in distal and proximal limbs and impaired sensory function in the extremities.3 The role of IG therapy for CIDP has been well-established4 and is considered a standard of care for this complex and heterogeneous condition in guidelines from the European Academy of Neurology and Peripheral Nerve Society due to its broad immunomodulatory and anti-inflammatory effects.5 Nearly a quarter of all IG therapy is used in the treatment of CIDP.6 About HYQVIA® HYQVIA® [Immune Globulin Infusion 10% (Human) with Recombinant Human Hyaluronidase] is a liquid medicine containing Recombinant Human Hyaluronidase and immunoglobulins (IG) and is approved by the European Medicines Agency (EMA) as a replacement therapy in adults, children and adolescents with primary immunodeficiency (PI) and with secondary immunodeficiency (SID) who suffer from severe or recurrent infections, ineffective antimicrobial treatment, and either proven specific antibody failure (PSAF) or serum IgG level of <4 g/L. In addition, it is approved by the EMA as maintenance therapy in adults, children and adolescents (0-18 years) with chronic inflammatory demyelinating polyneuropathy (CIDP) after stabilization with intravenous immunoglobulin therapy (IVIG). In the United States it is approved to treat adults and children two years of age and older with PI as a well as a maintenance therapy for adult patients with CIDP. HYQVIA is infused under the skin into the fatty subcutaneous tissue. HYQVIA contains IG collected from human plasma. IG are antibodies that maintain the body’s immune system. The hyaluronidase part of HYQVIA facilitates the dispersion and absorption of IG in the subcutaneous space between the skin and the muscle. HYQVIA is infused up to once a month (every two, three or four weeks for CIDP; every three or four weeks for PI). About the ADVANCE-CIDP 3 Clinical Trial ADVANCE-CIDP 3 was a long-term extension of ADVANCE-CIDP 1, a Phase 3, double-blind, randomized, placebo-controlled study.7 All patients entering ADVANCE-CIDP 3 received open-label HYQVIA and continued to receive the same dose and dosing regimen from ADVANCE-CIDP 1 (mean monthly dose equivalent of 1.1 g/kg).7 The primary objective was to analyze long-term safety, tolerability and immunogenicity. Efficacy was an exploratory outcome, including evaluation of CIDP relapse. Further information about the ADVANCE-CIDP 3 clinical trial is available at ClinicalTrials.gov under study identifier NCT02955355. HyQvia® (Human normal immunoglobulin) 100 mg/ml solution for infusion for subcutaneous use European PRESCRIBING INFORMATION Always refer to the Summary of Product Characteristics (SmPC) and the local prescribing information of your country before prescribing. Presentation: HyQvia is a dual vial unit consisting of one vial of 10% human normal immunoglobulin (Ig) and one vial of recombinant human hyaluronidase (see the SmPC for details). Indications: Replacement therapy in adults, children and adolescents (0-18 years) in: primary immunodeficiency syndromes (PID) with impaired antibody production; secondary immunodeficiencies (SID) in patients who suffer from severe or recurrent infections, ineffective antimicrobial treatment and either proven specific antibody failure (PSAF) or serum IgG level of <4 g/l. PSAF is a failure to mount at least a 2-fold rise in IgG antibody titre to pneumococcal polysaccharide and polypeptide antigen vaccines. Immunomodulatory therapy in adults, children and adolescents (0 to 18 years) in: chronic inflammatory demyelinating polyneuropathy (CIDP) as maintenance therapy after stabilization with IVIg. Dosage and administration: For subcutaneous use only. Therapy should be initiated and monitored under the supervision of a physician experienced in the treatment of immunodeficiency/CIDP. The product should be brought to room temperature before use. Inspect both vials for discolouration and particulate matter before administration. Do not use heating devices including microwaves. Do not shake or mix the components of the two vials. Suggested infusion site(s) are the middle to upper abdomen and thighs. The two components of the medicinal product must be administered sequentially through the same needle beginning with the recombinant human hyaluronidase followed by Ig 10%. Please see the SmPC for infusion rates. The full contents of the recombinant human hyaluronidase vial should be administered regardless of whether the full contents of the Ig 10% vial is administered. Longer needles may be used under medical supervision to prevent infusion site leakage. Home treatment should be initiated and monitored by a physician experienced in the guidance of patients for home treatment. Posology: Dose and dosage regimen may need to be individualised for each patient dependent on the response. The dose and dose regimens are dependent on the indication. Dose based on body weight may require adjustment in underweight or overweight patients. Replacement therapy in PID: Patients naïve to Ig therapy: The dose required to achieve a trough level of 6 g/L is approximately 0.4-0.8 g/kg body weight/month. The dose interval to maintain steady state levels varies from 2-4 weeks. IgG trough levels should be measured and assessed in conjunction with the incidence of infection. To reduce the rate of infection, it may be necessary to increase the dose and aim for higher trough levels (>6 g/l). At the initiation of therapy, it is recommended that the treatment intervals for the first infusions be gradually prolonged from a 1-week dose to up to a 3- or 4-week dose. Patients previously treated with intravenous (IV) Ig: For patients switching directly from IV Ig, or who have had a previous IV dose that can be referenced, the medicinal product should be administered at the same dose and at the same frequency as their previous IV Ig treatment. Patients previously treated with Ig administered subcutaneously: the initial dose of HyQvia is the same as for subcutaneous treatment but may be adjusted to 3- or 4-week intervals. The first infusion should be given one week after the last treatment with the previous Ig. Replacement therapy in SID: the recommended dose is 0.2-0.4 g/kg every 3 to 4 weeks. IgG levels should be measured and assessed in conjunction with the incidence of infection. Dose should be adjusted as necessary to achieve optimal protection against infections, an increase may be necessary in patients with persisting infection; a dose decrease can be considered when the patient remains infection free. Immunomodulatory therapy in CIDP: Before initiating therapy, the weekly equivalent dose should be calculated by dividing the planned dose by the planned dose interval in weeks. The typical dosing interval range for HyQvia is 3- to 4-weeks. The recommended subcutaneous dose is 0.3 to 2.4 g/kg body weight per month, administered in 1-or 2-sessions over 1-or 2-days. The patient's clinical response should be the primary consideration in dose adjustment. The dose may need to be adapted to achieve the desired clinical response. In clinical deterioration, the dose may be increased to the recommended maximum of 2.4 g/kg monthly. If the patient is clinically stable, periodic dose reductions may be needed to observe whether the patient still needs IG therapy. A titration schedule that permits gradual dose increase over time (ramp-up) is recommended to ensure the patient’s tolerability until the full dose is reached. During the titration schedule, the calculated HyQvia dose and recommended dose intervals must be followed for the first and second infusions. Depending on the treating physician's discretion, in patients who tolerate the first 2 infusions well, subsequent infusions may be administered by gradually increasing doses and dose intervals, considering the volume and total infusion time. An accelerated titration schedule may be considered if the patient tolerates the SC infusion volumes and the first 2 infusions. Doses less than or equal to 0.4 g/kg may be administered without a titration schedule, provided acceptable patient tolerance. Patients must be on stable doses (Variations in the dosing interval of up to ±7 days or monthly equivalent dose amount of up to ±20% between the subject’s IgG infusions are considered a stable dose) of IVIg. Before initiating therapy with the medicinal product, the weekly equivalent dose should be calculated by dividing the last IVIg dose by the IVIg dose interval in weeks. The starting dose and dosing frequency are the same as the patient’s previous IVIg treatment. The typical dosing interval for HyQvia is 4-weeks. For patients with less frequent IVIg dosing (greater than 4-weeks), the dosing interval can be converted to 4-weeks while maintaining the same monthly equivalent IgG dose. The calculated one-week dose (1st infusion) should be administered 2 - weeks after the last IVIg infusion (see Table 1 of the SmPC). One week after the first dose, the next weekly equivalent dose (2nd infusion) should be administered. A titration schedule can take up to 9-weeks (see Table 1 of the SmPC), depending on the dosing interval and tolerability. On a given infusion day, the maximum infusion volume should not exceed 1200 mL for patients weighing ≥40 kg or 600 mL for <40 kg. Suppose the maximum daily dose limit is exceeded or the patient cannot tolerate the infusion volume. In that case, the dose may be administered over multiple days in divided doses with 48-to 72-hours between doses to allow absorption of infusion fluid at the infusion site(s). The dose can be administered up to 3 infusion sites with a maximum infusion volume of 600 mL per site (or as tolerated). If using three sites, the maximum is 400 mL per site. Paediatric population: Replacement therapy and Immunomodulatory therapy: follow adult dosage guidance. Contraindications: Hypersensitivity to any ingredient or human IG especially in patients with antibodies against IgA; systemic hypersensitivity to hyaluronidase or human recombinant hyaluronidase; HyQvia must not be given IV or intramuscularly. Warnings and precautions: If HyQvia is accidentally administered into a blood vessel, patients could develop shock. The recommended infusion rate given in the SmPC should be adhered to. Infuse slowly and monitor closely throughout the infusion period, particularly patients starting therapy. Patients may require monitoring for up to 1 hour after administration. Manage infusion related events by slowing the infusion rate or stopping the infusion. Treatment will depend on the nature and severity of the adverse event. Patients should be reminded to report chronic inflammation and nodules which occur at the infusion site or other locations. For home treatment, patients should have the support of another responsible person in case of adverse reactions. Record treatment with HyQvia and batch number in patients’ notes. Hypersensitivity: Hypersensitivity reactions are possible in patients with anti-IgA antibodies who should only be treated with HyQvia if alternative treatments are not possible and under close medical supervision. In case of hypersensitivity, shock or anaphylactic-like reactions, discontinue the infusion immediately and treat the patient for shock. Rarely, human normal IG can induce a fall in blood pressure with anaphylactic reaction. In high-risk patients HyQvia should only be administered where supportive care is available for life threatening reactions. Patients should be informed of the early signs of anaphylaxis/ hypersensitivity. Pre-medication may be used as a preventative measure. Hypersensitivity to recombinant human hyaluronidase: Any suspicion of allergic or anaphylactic like reactions following recombinant human hyaluronidase administration requires immediate discontinuation of the infusion and standard medical treatment should be administered, if necessary. Immunogenicity of recombinant human hyaluronidase: Development of non-neutralising antibodies and neutralizing antibodies to the recombinant human hyaluronidase component has been reported in patients receiving HyQvia in clinical studies. Thromboembolism: Thromboembolic events including myocardial infarction, stroke, deep venous thrombosis and pulmonary embolism have been observed with IG treatment and cannot be excluded with use of HyQvia. Ensure adequate hydration prior to treatment. Monitor for signs and symptoms of thrombosis and assess blood viscosity in patients at risk. Patients should be informed about initial symptoms and advised to contact their physician immediately upon onset. Haemolytic anaemia: IG products contain antibodies to blood groups (e.g. A, B, D) which may act as haemolysins. Monitor for signs and symptoms of haemolysis. Aseptic meningitis syndrome: has been reported, symptoms usually begin within several hours to 2 days following treatment. Patients should be informed about initial symptoms. Discontinuation of IG treatment may result in remission within several days without sequelae. Interference with serological testing: After infusion of immunoglobulins, the transitory rise of the various passively transferred antibodies in the patient’s blood may result in misleading positive results in serological testing. Passive transmission of antibodies to erythrocyte´s surface antigens may interfere with some serological tests for red cell antibodies. Infusions of immunoglobulin products may lead to false positive readings in assays that depend on detection of β-D glucans for diagnosis of fungal infections. Transmissible agents: Infectious diseases due to the transmission of infective agents cannot be totally excluded. Sodium content: The recombinant human hyaluronidase component contains 4.03 mg sodium/mL. To be taken into consideration by patients on a controlled sodium diet. Traceability: The name and the batch number of the administered product should be clearly recorded. Interactions: Live attenuated virus vaccines – postpone vaccination for 3 months after treatment with HyQvia. For measles vaccine, impairment may persist for up to 1 year, so check antibody status. Please see the SmPC for details. Fertility, pregnancy and lactation: Safety during pregnancy has not been established and immunoglobulins are excreted into the milk, therefore use with caution in pregnant and breastfeeding mothers. Effects on ability to drive and use machines: The ability to drive and operate machines may be impaired by some adverse reactions e.g., dizziness associated with this medicinal product. Patients who experience adverse reactions during treatment should wait for these to resolve before driving or operating machines. Undesirable effects: Very common (≥1/10 patients): Headache, Blood pressure increased and Hypertension, Nauseam Diarrhoea, Vomiting, Arthralgia, Local reactions (Infusion site discomfort, Infusion site pain, Injection site pain, Puncture site pain and Tenderness; infusion site erythema and Injection site erythema; Infusion site oedema, Injection site oedema, infusion site swelling, Injection site swelling and Swelling (local), Feeling hot, Asthenia, Fatigue, Lethargy and Malaise. Common (≥1/100, <1/10 patients): Migraine, Tremor, Paraesthesia, Sinus tachycardia and Tachycardia, Hypotension, Dyspnoea, Abdominal distension, Erythema, Pruritus, Rash, Rash erythematous, Rash macular, Rash maculo-papular and Rash popular Urticaria, Myalgia, Limb discomfort and Pain in extremity, Back pain, Joint stiffness, Musculoskeletal chest pain, Groin pain, Hemosiderinuria, Infusion related reaction, Infusion site bruising, Injection site bruising, Infusion site haematoma, Injection site haematoma, Infusion site haemorrhage and Vessel puncture site bruise, Infusion site reaction, Injection site reaction and Puncture site reaction, Infusion site mass, Injection site mass and Infusion site nodule, Infusion site discoloration, Infusion site rash and Injection site rash, Infusion site induration and Injection site induration, Infusion site warmth, Infusion site paraesthesia and Injection site paraesthesia, Infusion site inflammation, Chills, Oedema, Oedema peripheral and Swelling (systemic), Localised oedema, Peripheral swelling and Skin oedema, Gravitational oedema, Oedema genital, Scrotal swelling and Vulvovaginal swelling, Hyperhidrosis, Coombs direct test positive and Coombs test positive. Uncommon (≥ 1/1 000 to < 1/100): Cerebrovascular accident and Ischaemic stroke, Burning sensations. Other undesirable effects (rare or unknown frequency): Meningitis aseptic, Hypersensitivity, Direct Coombs’ test positive, Infusion site leakage, Influenza-like illness. Refer to the SmPC for details on full side effect and interactions. Marketing Authorisation (MA) numbers: 2.5g EU/1/13/840/001, 5g EU/1/13/840/002, 10g EU/1/13/840/003, 20g EU/1/13/840/004, 30g EU/1/13/840/005. Name and address of MA holder: Baxalta Innovations GmbH, Industriestrasse 67, A-1221 Vienna, Austria. HyQvia is a registered trade name. PI approval code: PI-02941 Date of preparation: June 2024. Further information is available on request Adverse events should be reported to the authorities in your country as required by local law. Adverse events should also be reported to Takeda at: GPSE@takeda.com. For Full U.S. Prescribing Information, please visit: About Takeda Takeda is focused on creating better health for people and a brighter future for the world. We aim to discover and deliver life-transforming treatments in our core therapeutic and business areas, including gastrointestinal and inflammation, rare diseases, plasma-derived therapies, oncology, neuroscience and vaccines. Together with our partners, we aim to improve the patient experience and advance a new frontier of treatment options through our dynamic and diverse pipeline. As a leading values-based, R&D-driven biopharmaceutical company headquartered in Japan, we are guided by our commitment to patients, our people and the planet. Our employees in approximately 80 countries and regions are driven by our purpose and are grounded in the values that have defined us for more than two centuries. For more information, visit . 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Takeda does not undertake to update any of the forward-looking statements contained in this press release or any other forward-looking statements it may make, except as required by law or stock exchange rule. Past performance is not an indicator of future results and the results or statements of Takeda in this press release may not be indicative of, and are not an estimate, forecast, guarantee or projection of Takeda’s future results. Medical Information This press release contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development. References ___________________________________ 1 European Medicines Agency. HyQvia 100 mg/mL solution for infusion for subcutaneous use Summary of Product Characteristics. Available at . 2 Hadden R et al. Hyaluronidase-facilitated subcutaneous immunoglobulin 10% for chronic inflammatory demyelinating polyradiculoneuropathy: final results from a long-term safety and tolerability study. Poster presented at: Peripheral Nerve Society (PNS) Annual Meeting, 22–25 June 2024, Montréal, Canada. P89. 3 Dalakas MC; Medscape. Advances in the diagnosis, pathogenesis and treatment of CIDP. Nat Rev Neurol. 2011;7(9):507-517. 4 Eftimov F, et al. Intravenous immunoglobulin for chronic inflammatory demyelinating polyradiculoneuropathy. Cochrane Database Syst Rev. 2013;(12):CD001797. 5 Van den Bergh PYK, et al. European Academy of Neurology/Peripheral Nerve Society guideline on diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy: Report of a joint Task Force-Second revision [published correction appears in J Perpher Nerv System. 2022 Mar;27(1):94]. 6 Adivo 2020 data (incl. US, Canada, France, Germany, UK, Italy, Spain, Sweden, Netherlands, Japan, Taiwan, Australia, Brazil, Turkey, Russia, Argentina, Egypt, Kazakhstan, Saudi Arabia, Colombia) represents ~84% of Global IG Consumption (excl. China and India) 7 ClinicalTrials.gov. Long-Term Tolerability and Safety of HYQVIA/​HyQvia in CIDP. July 24, 2023. Last accessed May 2024 from

New MajesTEC-1 data show a median duration of response of 24 months, with responses deepening, including in patients who switched to biweekly dosing1 Separate analyses from the MajesTEC-1 and OPTec studies are the first to underscore the opportunity for outpatient administration of TECVAYLI® CHICAGO, June 3, 2024 /PRNewswire/ -- Johnson & Johnson today announced longer-term data from the pivotal Phase 1/2 MajesTEC-1 study of TECVAYLI® (teclistamab-cqyv) showing deep and durable responses in patients with relapsed or refractory multiple myeloma (RRMM) who are triple-class exposed (TCE)a and who previously received three or more prior lines of therapy, including in patients who switched to less frequent dosing (Abstract #7540).1 These data were featured at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting in a poster presentation.1 Additional presentations highlight the potential for outpatient step-up administration with prophylactic tocilizumab from the MajesTEC-1 study (Abstract #7517) and the first-in-class Phase 2 OPTec study (Abstract #7528), as well as first results from the subgroup analysis of patients with high-risk (HR) features that will be presented at the 2024 European Hematology Association (EHA) Congress (Abstract #923).2,3,4 The safety run-in MajesTEC-7 study in frontline TECVAYLI® administration (Abstract #7506) will also be presented at ASCO.4 "With the longest follow-up of any bispecific antibody, teclistamab demonstrates continued deep and durable responses observed in patients with relapsed or refractory multiple myeloma who have limited treatment options," said Niels van de Donk, M.D., Professor of Hematology at Amsterdam University Medical Centers, and principal study investigator.* "The results of the MajesTEC-1 study indicate the potential of teclistamab to transform the treatment paradigm, and clinical studies are investigating whether teclistamab may be a pivotal advancement for improved care and management in the broader patient population." Results from the MajesTEC-1 study show that, at a median follow-up of 30.4 months, patients treated with TECVAYLI® at the recommended Phase 2 dose (RP2D)b (n=165) demonstrated an overall response rate (ORR) of 63 percent, with responses continuing to deepen and 46 percent of patients achieving a complete response (CR) or better.1 For patients with a CR or better, mDOR, mPFS, and mOS were not yet reached, and estimated 30-month DOR, PFS, and OS rates were 61, 61 and 74 percent, respectively.1 Patients who achieved a partial response or better after a minimum of four cycles of therapy (Phase 1), or maintained a CR or better for a minimum of six months (Phase 2) per protocol, had the option to switch to biweekly dosing (every two weeks) (Q2W).1 Additionally, 37 out of 38 patients who switched to Q2W dosing maintained responses.1 The safety profile remained consistent, with a notable decrease in new onset of severe infections over time.1 Adverse events (AEs) included neutropenia (any grade, 72 percent; grade 3/4, 66 percent), anemia (any grade, 55 percent; grade 3/4, 38 percent), thrombocytopenia (any grade, 42 percent; grade 3/4, 23 percent), lymphopenia (any grade, 36 percent; grade 3/4, 35 percent), and infections (any grade, 79 percent; grade 3/4, 55 percent).1 Of 22 grade 5 infections, 18 were due to COVID-19.1 The decrease in new-onset grade 3 or greater infections may be due to switching to Q2W dosing or other factors such as implementing the use of intravenous immunoglobulin.1 "Over the past two years, TECVAYLI has helped over 10,000 patients with relapsed or refractory multiple myeloma," said Rachel Kobos, M.D., Vice President, Oncology Research & Development, Johnson & Johnson Innovative Medicine. "Through robust clinical data and real-world evidence, and by leveraging our team's expertise, we're working relentlessly to address unmet needs for patients with myeloma and drive the development of new treatment options for use across the treatment paradigm, including in the frontline setting." TECVAYLI® studies investigate outpatient administration in patients with RRMM, examining a more convenient approach to treatment, including in a community setting Extended follow-up of patients from a MajesTEC-1 cohort, investigating the prophylactic use of tocilizumab for the reduction of cytokine release syndrome (CRS) in patients treated with TECVAYLI®, were also presented at ASCO in an oral presentation (Abstract #7517).2 Results show a single dose of tocilizumab before TECVAYLI® in patients with RRMM (n=24) reduced the incidence of CRS with a 65 percent relative reduction versus the overall MajesTEC-1 population.2 This approach is continuing to be evaluated in the first-in-class Phase 2, multicenter, prospective OPTec study of TECVAYLI® in the community setting, presented as a poster presentation (Abstract #7528) at ASCO.3 Data showed preliminary evidence that prophylactic tocilizumab potentially reduces the incidence of CRS, with no new safety concerns to date and underscores the opportunity for outpatient administration.3 Evaluation of patients with high-risk multiple myeloma from MajesTEC-1 study shows clinical benefit from treatment with TECVAYLI® Subgroup analysis from the MajesTEC-1 study of TECVAYLI® investigating patients with HR RRMM will be presented at EHA (Abstract #923).4 Results show at a median follow-up of 30 months, patients who were aged 75 years or older, patients who had HR cytogenetics and patients who were penta-drug refractory demonstrated similar efficacy as the overall RP2D population with an ORR of 54 percent, 61 percent and 60 percent and a CR or better rate of 42 percent, 42 percent and 48 percent, respectively.4 The data demonstrate the clinical benefit of TECVAYLI® as an additional treatment option for some patients with HR features who typically face poor outcomes.4 The safety profile across subgroups was consistent with the RP2D population, including overall incidence and severity of TEAEs.4 Data from a single-arm run-in cohort of the Phase 3 MajesTEC-7 study shows early clinical profile of TECVAYLI®-based regimen in patients with transplant ineligible/not intended newly diagnosed multiple myeloma The results, presented in an oral presentation (Abstract #7506) at ASCO, of the first safety run-in (SRI) from a single-arm cohort of the Phase 3 MajesTEC-7 study provide preliminary data for a TECVAYLI®-based regimen in transplant- ineligible/not intended newly diagnosed multiple myeloma.5 Patients (n=26) received TECVAYLI® in combination with daratumumab and lenalidomide (DR).5 At a median follow-up of 13.8 months, the ORR was 92 percent, with 23 patients remaining on treatment.5 Treatment-emergent adverse events (TEAEs) occurred in 100 percent of patients, where 61.5 percent of patients experienced grade 1/2 CRS in cycle one - all of which resolved.5 About the MajesTEC-1 Study MajesTEC-1 (NCT03145181, NCT04557098) is a Phase 1/2 single-arm, open-label, multicohort, multicenter dose-escalation study evaluating the safety and efficacy of teclistamab in adults with RRMM who received three or more prior lines of therapy.6,7 Phase 1 of the study (NCT03145181) was conducted in two parts: dose escalation (Part 1) and dose expansion (Part 2).6 It evaluated safety, tolerability, pharmacokinetics, and preliminary efficacy of teclistamab in adult participants with RRMM.6 Phase 2 of the study (NCT04557098) evaluated the efficacy of teclistamab at the RP2D, established at subcutaneous 1.5 mg/kg weekly, as measured by ORR. About the OPTec Study OPTec (NCT05972135) is a Phase 2, single-arm, non-randomized, multicenter, prospective study evaluating the use of prophylactic tocilizumab in patients with RRMM to reduce the incidence and severity of CRS associated with administration of the step-up dosing regimen of teclistamab in the outpatient setting. About the MajesTEC-7 Study MajesTEC-7 (NCT05552222), is a Phase 3 randomized study, comparing teclistamab in combination with daratumumab SC and lenalidomide (Tec-DR) and talquetamab in combination with daratumumab SC and lenalidomide (Tal-DR) versus daratumumab SC, lenalidomide, and dexamethasone (DRd) in participants with newly diagnosed multiple myeloma who are either ineligible or not intended for autologous stem cell transplant as initial therapy.8 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.2 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 least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody, and have demonstrated disease progression since the last therapy. 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 1.5 mg/kg every two weeks in patients who have achieved a complete response (CR) or better for a minimum of six months. TECVAYLI® is a first-in-class, bispecific T-cell engager antibody therapy that 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. In February 2024, the U.S. FDA approved the supplemental Biologics License Application (sBLA) for TECVAYLI® for a reduced dosing frequency of 1.5 mg/kg every two weeks (Q2W) in patients with relapsed or refractory multiple myeloma who have achieved and maintained a CR or better for a minimum of six months. 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.9 In multiple myeloma, these plasma cells proliferate and spread rapidly and replace normal cells in the bone marrow with tumors.10 Multiple myeloma is the third most common blood cancer worldwide and remains an incurable disease.11 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.12 People living with multiple myeloma have a 5-year survival rate of 59.8 percent.13 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.14,15 TECVAYLI® IMPORTANT SAFETY INFORMATION INDICATION AND USAGE TECVAYLI® (teclistamab-cqyv) is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager indicated 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 monoclonal antibody. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). WARNINGS AND PRECAUTIONS Cytokine 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 REACTIONS The 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®. 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 and Janssen Biotech, Inc. are both 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 TECVAYLI® (teclistamab-cqyv). 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., 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., nor Johnson & Johnson undertake to update any forward-looking statement as a result of new information or future events or developments. * Niels van de Donk, M.D., Professor of Hematology at Amsterdam University Medical Centers, and principal study investigator has provided consulting, advisory, and speaking services to Johnson & Johnson; he has not been paid for any media work. a Triple-class exposed (TCE): patients who have previously received an immunomodulatory agent (IMiD), a proteasome inhibitor (PI), and an anti-CD38 monoclonal antibody (mAb). b Recommended Phase 2 dose (RP2D): dose of a drug that was identified in a Phase 1 study (dose finding study). 1 Garfall, A., et al. Long-term follow-up from the phase 1/2 MajesTEC-1 trial of teclistamab in patients with relapsed/refractory multiple myeloma. 2024 ASCO Annual Meeting – American Society of Clinical Oncology. June 2024. 2 Van de Donk, N., et al. Longer-term follow-up of patients (pts) receiving prophylactic tocilizumab (toci) for the reduction of cytokine release syndrome (CRS) in the phase ½ MajesTEC-1 study of teclistamab in relapsed/refractory multiple myeloma (RRMM). 2024 ASCO Annual Meeting – American Society of Clinical Oncology. June 2024. 3 Rifkin, R., et al. OPTec: A phase 2 study to evaluate outpatient (OP) step-up administration of teclistamab (Tec), a BCMA-targeting bispecific antibody, in patients (pts) with relapsed/refractory multiple myeloma (RRMM). 4 Costa, L., et al. Efficacy and safety of teclistamab in patients with relapsed/refractory multiple myeloma with high-risk features: A subgroup analysis from the phase 1/2 MajesTEC-1 study. 2024 EHA Hybrid Congress – European Hematology Association. June 2024 5 Touzeau, C., et al. Safety results from the phase 3 MajesTEC-7 study in patients (pts) with transplant ineligible/not intended newly diagnosed multiple myeloma (NDMM). 2024 ASCO Annual Meeting – American Society of Clinical Oncology. June 2024. 6 A Study of Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma (MajesTEC-1). . Accessed June 2024. 7 Dose Escalation Study of Teclistamab, a Humanized BCMA*CD3 Bispecific Antibody, in Participants With Relapsed or Refractory Multiple Myeloma (MajesTEC-1). . Accessed June 2024. 8 A Study of Teclistamab in Combination With Daratumumab and Lenalidomide (Tec-DR) and Talquetamab in Combination With Daratumumab and Lenalidomide (Tal-DR) in Participants With Newly Diagnosed Multiple Myeloma (MajesTEC-7). . Accessed June 2024. 9 Rajkumar SV. Multiple myeloma: 2020 update on diagnosis, risk-stratification and management. Am J Hematol. 2020;95(5):548-5672020;95(5):548-567. 10 National Cancer Institute. Plasma Cell Neoplasms. . Accessed February 2024. 11 City of Hope. Multiple Myeloma: Causes, Symptoms & Treatments. . Accessed June 2024. 12 American Cancer Society. Key Statistics About Multiple Myeloma. . Accessed June 2024. 13 SEER Explorer: An interactive website for SEER cancer statistics [Internet]. Surveillance Research Program, National Cancer Institute. . Accessed June 2024. 14 American Cancer Society. What is Multiple Myeloma? . Accessed June 2024. 15 American Cancer Society. Multiple Myeloma Early Detection, Diagnosis, and Staging . Accessed June 2024. SOURCE Johnson & Johnson

FDA ODAC unanimously votes 11 to 0 supporting favorable risk-benefit assessment of CARVYKTI® based on results from the Phase 3 CARTITUDE-4 study RARITAN, N.J., March 15, 2024 /PRNewswire/ -- Johnson & Johnson announced today that the U.S. Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) recommends CARVYKTI® (ciltacabtagene autoleucel, cilta-cel) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) and who are refractory to lenalidomide. The committee reviewed survival and safety data from the Phase 3 CARTITUDE-4 study and voted unanimously in favor of CARVYKTI® (11 to 0) finding the risk-benefit assessment of CARVYKTI® for the proposed indication as favorable. A supplemental Biologics License Application (sBLA) supported by the CARTITUDE-4 study is currently under review by the FDA with a Prescription Drug User Fee Act (PDUFA) date of April 5, 2024. "We are pleased with the advisory committee's support for CARVYKTI in earlier lines of treatment based on the CARTITUDE-4 data," said Jordan Schecter, M.D., Vice President, Disease Area Leader, Multiple Myeloma, Johnson & Johnson Innovative Medicine. "As a physician and researcher committed to advancing patient care, the potential of CARVYKTI in earlier lines of therapy represents an important therapeutic option for patients with multiple myeloma." The committee reviewed data from the CARTITUDE-4 study, the first randomized Phase 3 study of CARVYKTI®, which evaluated the efficacy and safety of CARVYKTI® versus pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) in the treatment of patients with relapsed and lenalidomide-refractory multiple myeloma who received one to three prior lines of therapy.1 These data also served as the basis for the recent European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) positive opinion of a Type II variation for CARVYKTI® in the treatment of patients with relapsed and refractory multiple myeloma who have received at least one prior therapy, including an IMiD and a PI, and are refractory to lenalidomide.2 Results from the CARTITUDE-4 study were initially presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting and published in The New England Journal of Medicine.1,3 "Multiple myeloma is a disease with high unmet need as patients experience relapse or become refractory to treatments over time," said Sundar Jagannath, M.D., Director of the Center of Excellence for Multiple Myeloma and Professor of Medicine, Hematology and Medical Oncology, Mount Sinai.‡ "The availability of a cellular therapy like cilta-cel that can be used earlier in the treatment of this progressive disease is critically important, offering patients a chance of deep and durable responses with a one-time infusion." The ODAC is convened upon request of the FDA to review and evaluate safety and efficacy data of human drug products for use in the treatment of oncologic diseases. The committee provides non-binding recommendations based on its evaluation; however, final decisions on approval of the drug are made by the FDA. About CARVYKTI® (ciltacabtagene autoleucel; cilta-cel) CARVYKTI® 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 PI, an IMiD agent, and an anti-CD38 monoclonal antibody.4 In May 2022, the European Commission granted conditional marketing authorization of CARVYKTI® for the treatment of adults with relapsed and refractory multiple myeloma who have received at least three prior therapies, including an IMiD agent, a PI 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 . 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.5 In multiple myeloma, these plasma cells proliferate and spread rapidly and replace normal cells in the bone marrow with tumors.6 Multiple myeloma is the third most common blood cancer worldwide and remains an incurable disease.7 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.8 People living with multiple myeloma have a 5-year survival rate of 59.8 percent.9 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.10,11 CARVYKTI® IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Cytokine 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 C-reactive 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 CARTITUDE-1. 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 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 COVID-19 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 REACTIONS The 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®. 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 and Janssen Biotech, Inc. are both Johnson & Johnson companies. ‡ Dr. Sundar Jagannath has provided consulting, advisory, and speaking services to Johnson & Johnson; he has not been paid for any media work. 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). 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., 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., nor Johnson & Johnson undertake to update any forward-looking statement as a result of new information or future events or developments. 1 Dhakal, B. First phase 3 results from CARTITUDE-4: Cilta-cel versus standard of care (PVd or DPd) in lenalidomide-refractory multiple myeloma. Abstract #LBA106 [Oral Presentation]. Presented at the 2023 American Society of Clinical Oncology Annual Meeting. 2 Janssen receives positive CHMP opinion for CARVYKTI (ciltacabtagene autoleutcel; cilta-cel) for treatment in earlier lines of relapsed and refractory multiple myeloma. Johnson & Johnson Innovative Medicine. . Accessed March 2024. 3 Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma. New England Journal of Medicine. . Accessed March 2024. 4 CARVYKTI® Prescribing Information. Horsham, PA: Janssen Biotech, Inc. 5 Rajkumar SV. Multiple myeloma: 2020 update on diagnosis, risk-stratification and management. Am J Hematol. 2020;95(5):548-5672020;95(5):548-567. 6 National Cancer Institute. Plasma Cell Neoplasms. . Accessed March 2024. 7 City of Hope. Multiple Myeloma: Causes, Symptoms & Treatments. . Accessed March 2024. 8 American Cancer Society. Key Statistics About Multiple Myeloma. . Accessed March 2024. 9 SEER Explorer: An interactive website for SEER cancer statistics [Internet]. Surveillance Research Program, National Cancer Institute. . Accessed March 2024. 10 American Cancer Society. What is Multiple Myeloma? . Accessed March 2024. 11 American Cancer Society. Multiple Myeloma Early Detection, Diagnosis, and Staging. . Accessed March 2024. SOURCE Johnson & Johnson