- Landmark CARTITUDE-4 research outcomes present CARVYKTI ® lowered the danger of dying by 45 % after three-year follow-up
- Late-breaking information featured in an oral presentation on the 21st Worldwide Myeloma Society Annual Assembly
SOMERSET, N.J., Sept. 27, 2024 (GLOBE NEWSWIRE) — Legend Biotech Company (NASDAQ: LEGN) (Legend Biotech), a worldwide chief in cell remedy, at the moment introduced late-breaking three-year follow-up information from the Section 3 CARTITUDE-4 research that reveals a single infusion of CARVYKTI ® (ciltacabtagene autoleucel) considerably prolonged total survival (OS) in sufferers with relapsed or lenalidomide-refractory a number of myeloma who’ve obtained no less than one prior line of remedy, together with a proteasome inhibitor (PI), and an immunomodulatory agent (IMiD), lowering the danger of dying by 45 % versus customary therapies of pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd).1 CARVYKTI ® is now the primary and solely cell remedy to enhance OS versus customary therapies for sufferers with lenalidomide-refractory a number of myeloma as early as second line.1 These outcomes had been offered as a late-breaking oral presentation on the 2024 Worldwide Myeloma Society (IMS) Annual Assembly (Summary #OA-65) in Rio de Janeiro, Brazil.1
These long-term outcomes are groundbreaking and display that CARVYKTI considerably extends sufferers’ total survival and meaningly improves their high quality of life, mentioned Maria-Victoria Mateos, M.D., Ph.D., Guide Doctor within the Hematology Division and Affiliate Professor of Medication on the College of Salamanca, Spain. These information present that with a single infusion, we will cut back the danger of dying and supply a number of myeloma sufferers the chance to stay longer. ¡
These information underscore Legend’s dedication to offering sufferers with efficient therapies which have the potential to enhance their high quality of life and lengthen survival, mentioned Ying Huang, Ph.D., Chief Govt Officer of Legend Biotech. We’ll proceed to research the advantages CAR-T can deliver to sufferers by investing considerably in R&D and exploring the complete spectrum of CAR-T applied sciences.
The Section 3 CARTITUDE-4 research evaluated CARVYKTI ® in comparison with customary therapies of PVd or DPd for the remedy of sufferers with relapsed or lenalidomide-refractory a number of myeloma after one prior line of remedy.1 Sufferers who obtained one to 3 prior traces of remedy, together with a PI and IMiD, and had been lenalidomide-refractory had been randomized [cilta-cel, n=208, standard therapies, n=211].1 At median follow-up of virtually three years (34 months), median OS was not reached [NR] for sufferers within the CARVYKTI ® arm (95 % Confidence Interval [CI], not estimable (NE) “ NE) or sufferers that obtained customary therapies (95 % CI, 37.75 months “ NE) (Hazard Ratio [HR], 0.55; 95 % CI, 0.39-0.79, P=0.0009).1 At 30-months comply with up, OS charges had been 76 % for sufferers within the CARVYKTI ® arm and 64 % for sufferers handled with customary therapies.1 These information present CARVYKTI ® considerably prolonged OS for sufferers in comparison with customary therapies.1
In sufferers randomized to the CARVYKTI ® arm, CARVYKTI ® lowered the danger of dying by 45 % in comparison with customary therapies demonstrating clinically significant responses for sufferers as early as after first relapse.1 Median progression-free survival (PFS) was NR within the CARVYKTI ® arm (95 % CI, 34.50 months “ NE) and 11.79 months (95 % CI, 9.66-14.00) in sufferers handled with customary therapies demonstrating sustained deep and sturdy responses.1 Sufferers within the CARVYKTI ® arm had a 77 % full response or higher, and 85 % total response fee. Sufferers within the CARVYKTI ® arm had 62 % minimal residual illness (MRD)negativity at 10-5 and 57 % MRD-negativity at 10-6, in comparison with sufferers handled with customary therapies (18.5 %, 9 %), respectively.1 Median period of response was NR (95 % CI, NE-NE) within the CARVYKTI ® arm and 18.69 months (95 % CI, 12.91-23.72) for sufferers handled with customary therapies.1 Median time to symptom worsening primarily based on A number of Myeloma Symptom and Influence Questionnaire (MySlm-Q) was NR (95 % CI, NE-NE) with CARVYKTI ® and 34.33 months (95 % CI, 32.20-NE) with sufferers handled with customary therapies (HR, 0.38, 95 % CI, 0.24-0.61; p<0.0001).1
The protection profile of cilta-cel versus customary therapies was in line with earlier outcomes. Within the security evaluation [cilta-cel, n=208, standard therapies, n=208], 97 % of sufferers in each arms skilled grade 3/4 treatment-emergent opposed occasions (TEAEs) with cytopenia being the commonest.1 Therapy-emergent infections occurred in 63 % of sufferers within the CARVYKTI ® arm and 76 % of sufferers who obtained customary therapies with 28 % and 30 % being categorised as grade 3/4, respectively.1 Within the CARVYKTI ® arm, there have been seven sufferers with hematologic second main malignancies, 50 sufferers died and 21 of these sufferers died because of progressive illness.1 Amongst sufferers that obtained customary therapies, one affected person skilled a hematologic second main malignancy, 82 sufferers died and of these sufferers, 51 had been because of progressive illness.1
Information from CARTITUDE-4 supported the U.S. Meals and Drug Administration (FDA) and European Fee approval of CARVYKTI ® earlier this 12 months for the remedy of grownup sufferers with relapsed or refractory a number of myeloma who’ve obtained no less than one prior line of remedy together with a PI, IMiD, and are refractory to lenalidomide. Globally, now we have now launched CARVYKTI ® in 5 international locations and handled greater than 3,500 sufferers.
CARVYKTI ® IMPORTANT SAFETY INFORMATION
| WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, PROLONGED and RECURRENT CYTOPENIA, and SECONDARY HEMATOLOGICAL MALIGNANCIES |
| Cytokine Launch Syndrome (CRS), together with deadly or life-threatening reactions, occurred in sufferers following remedy with CARVYKTI ®. Don’t administer CARVYKTI ® to sufferers with lively an infection or inflammatory problems. Deal with extreme or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids. |
| Immune Effector Cell-Related Neurotoxicity Syndrome (ICANS), which can be deadly or life-threatening, occurred following remedy with CARVYKTI ®, together with earlier than CRS onset, concurrently with CRS, after CRS decision, or within the absence of CRS. Monitor for neurologic occasions after remedy with CARVYKTI ®. Present supportive care and/or corticosteroids as wanted. |
| Parkinsonism and Guillain-Barré syndrome (GBS) and their related issues leading to deadly or life-threatening reactions have occurred following remedy with CARVYKTI ®. |
| Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS), together with deadly and life-threatening reactions, occurred in sufferers following remedy with CARVYKTI ®. HLH/MAS can happen with CRS or neurologic toxicities. |
| Extended and/or recurrent cytopenias with bleeding and an infection and requirement for stem cell transplantation for hematopoietic restoration occurred following remedy with CARVYKTI ®. |
| Secondary hematological malignancies, together with myelodysplastic syndrome and acute myeloid leukemia, have occurred in sufferers following remedy with CARVYKTI ®. T-cell malignancies have occurred following remedy of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies, together with CARVYKTI ®. |
| CARVYKTI ® is obtainable solely by means of a restricted program underneath a Threat Analysis and Mitigation Technique (REMS) referred to as the CARVYKTI ® REMS Program. |
WARNINGS AND PRECAUTIONS
INCREASED EARLY MORTALITY – In CARTITUDE-4, a (1:1) randomized managed trial, there was a numerically greater proportion of early deaths in sufferers randomized to the CARVYKTI ® remedy arm in comparison with the management arm. Amongst sufferers with deaths occurring throughout the first 10 months from randomization, a higher proportion (29/208; 14%) occurred within the CARVYKTI ® arm in comparison with (25/211; 12%) within the management arm. Of the 29 deaths that occurred within the CARVYKTI ® arm throughout the first 10 months of randomization, 10 deaths occurred previous to CARVYKTI ® infusion, and 19 deaths occurred after CARVYKTI ® infusion. Of the ten deaths that occurred previous to CARVYKTI ® infusion, all occurred because of illness development, and none occurred because of opposed occasions. Of the 19 deaths that occurred after CARVYKTI ® infusion, 3 occurred because of illness development, and 16 occurred because of opposed occasions. The most typical opposed occasions had been because of an infection (n=12).
CYTOKINE RELEASE SYNDROME (CRS), together with deadly or life-threatening reactions, occurred following remedy with CARVYKTI ®. Amongst sufferers receiving CARVYKTI ® for RRMM within the CARTITUDE-1 & 4 research (N=285), CRS occurred in 84% (238/285), together with ‰¥ Grade 3 CRS (ASCT 2019) in 4% (11/285) of sufferers. Median time to onset of CRS, any grade, was 7 days (vary: 1 to 23 days). CRS resolved in 82% with a median period of 4 days (vary: 1 to 97 days). The most typical manifestations of CRS in all sufferers mixed ( ‰¥ 10%) included fever (84%), hypotension (29%) and aspartate aminotransferase elevated (11%). Critical occasions that could be related to CRS embody pyrexia, hemophagocytic lymphohistiocytosis, respiratory failure, disseminated intravascular coagulation, capillary leak syndrome, and supraventricular and ventricular tachycardia. CRS occurred in 78% of sufferers in CARTITUDE-4 (3% Grade 3 to 4) and in 95% of sufferers in CARTITUDE-1 (4% Grade 3 to 4). Determine CRS primarily based on medical presentation. Consider for and deal with different causes of fever, hypoxia, and hypotension. CRS has been reported to be related to findings of HLH/MAS, and the physiology of the syndromes might overlap. HLH/MAS is a probably life-threatening situation. In sufferers with progressive signs of CRS or refractory CRS regardless of remedy, consider for proof of HLH/MAS. Please see Part 5.4; Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS).
Be certain that a minimal of two doses of tocilizumab can be found previous to infusion of CARVYKTI ®.
Of the 285 sufferers who obtained CARVYKTI ® in medical trials, 53% (150/285) sufferers obtained tocilizumab; 35% (100/285) obtained a single dose, whereas 18% (50/285) obtained greater than 1 dose of tocilizumab. Total, 14% (39/285) of sufferers obtained no less than one dose of corticosteroids for remedy of CRS.
Monitor sufferers no less than every day for 10 days following CARVYKTI ® infusion at a REMS-certified healthcare facility for indicators and signs of CRS. Monitor sufferers for indicators or signs of CRS for no less than 4 weeks after infusion. On the first signal of CRS, instantly institute remedy with supportive care, tocilizumab, or tocilizumab and corticosteroids.
Counsel sufferers to hunt rapid medical consideration ought to indicators or signs of CRS happen at any time.
NEUROLOGIC TOXICITIES, which can be extreme, life-threatening, or deadly, occurred following remedy with CARVYKTI ®. Neurologic toxicities included ICANS, neurologic toxicity with indicators and signs of parkinsonism, GBS, immune mediated myelitis, peripheral neuropathies, and cranial nerve palsies. Counsel sufferers on the indicators and signs of those neurologic toxicities, and on the delayed nature of onset of a few of these toxicities. Instruct sufferers to hunt rapid medical consideration for additional evaluation and administration if indicators or signs of any of those neurologic toxicities happen at any time.
Amongst sufferers receiving CARVYKTI ® within the CARTITUDE-1 & 4 research for RRMM, a number of neurologic toxicities occurred in 24% (69/285), together with ‰¥ Grade 3 instances in 7% (19/285) of sufferers. Median time to onset was 10 days (vary: 1 to 101) with 63/69 (91%) of instances creating by 30 days. Neurologic toxicities resolved in 72% (50/69) of sufferers with a median period to decision of 23 days (vary: 1 to 544). Of sufferers creating neurotoxicity, 96% (66/69) additionally 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 sufferers.
Immune Effector Cell-Related Neurotoxicity Syndrome (ICANS): Sufferers receiving CARVYKTI ® might expertise deadly or life-threatening ICANS following remedy with CARVYKTI ®, together with earlier than CRS onset, concurrently with CRS, after CRS decision, or within the absence of CRS.
Amongst sufferers receiving CARVYKTI ® within the CARTITUDE-1 & 4 research, ICANS occurred in 13% (36/285), together with Grade ‰¥3 in 2% (6/285) of the sufferers. Median time to onset of ICANS was 8 days (vary: 1 to twenty-eight days). ICANS resolved in 30 of 36 (83%) of sufferers with a median time to decision of three days (vary: 1 to 143 days). Median period of ICANS was 6 days (vary: 1 to 1229 days) in all sufferers together with these with ongoing neurologic occasions on the time of dying or information cut-off. Of sufferers with ICANS, 97% (35/36) had CRS. The onset of ICANS occurred throughout CRS in 69% of sufferers, earlier than and after the onset of CRS in 14% of sufferers respectively.
Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS) occurred in 7% of sufferers in CARTITUDE-4 (0.5% Grade 3) and in 23% of sufferers in CARTITUDE-1 (3% Grade 3). Essentially the most frequent ‰¥2% manifestations of ICANS included encephalopathy (12%), aphasia (4%), headache (3%), motor dysfunction (3%), ataxia (2%), and sleep problem (2%) [see Adverse Reactions (6.1)].
Monitor sufferers no less than every day for 10 days following CARVYKTI ® infusion on the REMS-certified healthcare facility for indicators and signs of ICANS. Rule out different causes of ICANS signs. Monitor sufferers for indicators or signs of ICANS for no less than 4 weeks after infusion and deal with promptly. Neurologic toxicity must be managed with supportive care and/or corticosteroids as wanted [see Dosage and Administration (2.3)].
Parkinsonism: Neurologic toxicity with parkinsonism has been reported in medical trials of CARVYKTI ®. Amongst sufferers receiving CARVYKTI ® within the CARTITUDE-1 & 4 research, parkinsonism occurred in 3% (8/285), together with Grade ‰¥ 3 in 2% (5/285) of the sufferers. Median time to onset of parkinsonism was 56 days (vary: 14 to 914 days). Parkinsonism resolved in 1 of 8 (13%) of sufferers with a median time to decision of 523 days. Median period of parkinsonism was 243.5 days (vary: 62 to 720 days) in all sufferers together with these with ongoing neurologic occasions on the time of dying or information cut-off. The onset of parkinsonism occurred after CRS for all sufferers and after ICANS for six sufferers.
Parkinsonism occurred in 1% of sufferers in CARTITUDE-4 (no Grade 3 to 4) and in 6% of sufferers in CARTITUDE-1 (4% Grade 3 to 4).
Manifestations of parkinsonism included motion problems, cognitive impairment, and character modifications. Monitor sufferers for indicators and signs of parkinsonism that could be delayed in onset and managed with supportive care measures. There’s restricted efficacy data with medicines used for the remedy of Parkinson’s illness for the advance or decision of parkinsonism signs following CARVYKTI ® remedy.
Guillain-Barré Syndrome: A deadly consequence following GBS occurred following remedy with CARVYKTI ® regardless of remedy with intravenous immunoglobulins. Signs reported embody these in line with Miller-Fisher variant of GBS, encephalopathy, motor weak point, speech disturbances, and polyradiculoneuritis.
Monitor for GBS. Consider sufferers presenting with peripheral neuropathy for GBS. Think about remedy of GBS with supportive care measures and along with immunoglobulins and plasma trade, relying on severity of GBS.
Immune Mediated Myelitis: Grade 3 myelitis occurred 25 days following remedy with CARVYKTI ® in CARTITUDE-4 in a affected person who obtained CARVYKTI ® as subsequent remedy. Signs reported included hypoesthesia of the decrease extremities and the decrease stomach with impaired sphincter management. Signs improved with the usage of corticosteroids and intravenous immune globulin. Myelitis was ongoing on the time of dying from different trigger.
Peripheral Neuropathy occurred following remedy with CARVYKTI ®. Amongst sufferers receiving CARVYKTI ® within the CARTITUDE-1 & 4 research, peripheral neuropathy occurred in 7% (21/285), together with Grade ‰¥3 in 1% (3/285) of the sufferers. Median time to onset of peripheral neuropathy was 57 days (vary: 1 to 914 days). Peripheral neuropathy resolved in 11 of 21 (52%) of sufferers with a median time to decision of 58 days (vary: 1 to 215 days). Median period of peripheral neuropathy was 149.5 days (vary: 1 to 692 days) in all sufferers together with these with ongoing neurologic occasions on the time of dying or information cut-off.
Peripheral neuropathies occurred in 7% of sufferers in CARTITUDE-4 (0.5% Grade 3 to 4) and in 7% of sufferers in CARTITUDE-1 (2% Grade 3 to 4). Monitor sufferers for indicators and signs of peripheral neuropathies. Sufferers who expertise peripheral neuropathy may expertise cranial nerve palsies or GBS.
Cranial Nerve Palsies occurred following remedy with CARVYKTI ®. Amongst sufferers receiving CARVYKTI ® within the CARTITUDE-1 & 4 research, cranial nerve palsies occurred in 7% (19/285), together with Grade ‰¥3 in 1% (1/285) of the sufferers. Median time to onset of cranial nerve palsies was 21 days (vary: 17 to 101 days). Cranial nerve palsies resolved in 17 of 19 (89%) of sufferers with a median time to decision of 66 days (vary: 1 to 209 days). Median period of cranial nerve palsies was 70 days (vary: 1 to 262 days) in all sufferers together with these with ongoing neurologic occasions on the time of dying or information cut-off. Cranial nerve palsies occurred in 9% of sufferers in CARTITUDE-4 (1% Grade 3 to 4) and in 3% of sufferers in CARTITUDE-1 (1% Grade 3 to 4).
Essentially the most frequent cranial nerve affected was the seventh cranial nerve. Moreover, cranial nerves III, V, and VI have been reported to be affected.
Monitor sufferers for indicators and signs of cranial nerve palsies. Think about administration with systemic corticosteroids, relying on the severity and development of indicators and signs.
HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS (HLH)/MACROPHAGE ACTIVATION SYNDROME (MAS): Amongst sufferers receiving CARVYKTI ® within the CARTITUDE-1 & 4 research, HLH/MAS occurred in 1% (3/285) of sufferers. All occasions of HLH/MAS had onset inside 99 days of receiving CARVYKTI ®, with a median onset of 10 days (vary: 8 to 99 days) and all occurred within the setting of ongoing or worsening CRS. The manifestations of HLH/MAS included hyperferritinemia, hypotension, hypoxia with diffuse alveolar injury, coagulopathy and hemorrhage, cytopenia, and multi-organ dysfunction, together with renal dysfunction and respiratory failure.
Sufferers who develop HLH/MAS have an elevated danger of extreme bleeding. Monitor hematologic parameters in sufferers with HLH/MAS and transfuse per institutional pointers. Deadly instances of HLH/MAS occurred following remedy with CARVYKTI ®.
HLH is a life-threatening situation with a excessive mortality fee if not acknowledged and handled early. Therapy of HLH/MAS must be administered per institutional requirements.
CARVYKTI ® REMS: Due to the danger of CRS and neurologic toxicities, CARVYKTI ® is obtainable solely by means of a restricted program underneath a Threat Analysis and Mitigation Technique (REMS) referred to as the CARVYKTI ® REMS.
Additional data is obtainable at https://www.carvyktirems.com or 1-844-672-0067.
PROLONGED AND RECURRENT CYTOPENIAS: Sufferers might exhibit extended and recurrent cytopenias following lymphodepleting chemotherapy and CARVYKTI ® infusion. Amongst sufferers receiving CARVYKTI ® within the CARTITUDE-1 & 4 research, Grade 3 or greater cytopenias not resolved by day 30 following CARVYKTI ® infusion occurred in 62% (176/285) of the sufferers 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 sufferers had a recurrence of Grade 3 or 4 lymphopenia, neutropenia, thrombocytopenia, and anemia respectively, after preliminary restoration of their Grade 3 or 4 cytopenia. Seventy-seven % (219/285) of sufferers had one, two, or three or extra recurrences of Grade 3 or 4 cytopenias after preliminary restoration of Grade 3 or 4 cytopenia. Sixteen and 25 sufferers had Grade 3 or 4 neutropenia and thrombocytopenia, respectively, on the time of dying.
Monitor blood counts previous to and after CARVYKTI ® infusion. Handle cytopenias with development elements and blood product transfusion assist in accordance with native institutional pointers.
INFECTIONS: CARVYKTI ® shouldn’t be administered to sufferers with lively an infection or inflammatory problems. Extreme, life-threatening, or deadly infections, occurred in sufferers after CARVYKTI ® infusion.
Amongst sufferers receiving CARVYKTI ® within the CARTITUDE-1 & 4 research, infections occurred in 57% (163/285), together with ‰¥Grade 3 in 24% (69/285) of sufferers. 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 sufferers. Total, 5% (13/285) of sufferers had Grade 5 infections, 2.5% of which had been because of COVID-19. Sufferers handled with CARVYKTI ® had an elevated fee of deadly COVID-19 infections in comparison with the usual remedy arm.
Monitor sufferers for indicators and signs of an infection earlier than and after CARVYKTI ® infusion and deal with sufferers appropriately. Administer prophylactic, pre-emptive, and/or therapeutic antimicrobials in accordance with the usual institutional pointers. Febrile neutropenia was noticed in 5% of sufferers after CARVYKTI ® infusion and could also be concurrent with CRS. Within the occasion of febrile neutropenia, consider for an infection and handle with broad-spectrum antibiotics, fluids, and different supportive care, as medically indicated. Counsel sufferers on the significance of prevention measures. Observe institutional pointers for the vaccination and administration of immunocompromised sufferers with COVID-19.
Viral Reactivation: Hepatitis B virus (HBV) reactivation, in some instances leading to fulminant hepatitis, hepatic failure, and dying, can happen in sufferers with hypogammaglobulinemia. Carry out screening for Cytomegalovirus (CMV), HBV, hepatitis C virus (HCV), human immunodeficiency virus (HIV), or some other infectious brokers if clinically indicated in accordance with medical pointers earlier than assortment of cells for manufacturing. Think about antiviral remedy to stop viral reactivation per native institutional pointers/medical apply.
HYPOGAMMAGLOBULINEMIA: can happen in sufferers receiving remedy with CARVYKTI ®. Amongst sufferers receiving CARVYKTI ® within the CARTITUDE-1 & 4 research, hypogammaglobulinemia opposed occasion was reported in 36% (102/285) of sufferers; laboratory IgG ranges fell under 500mg/dl after infusion in 93% (265/285) of sufferers.
Hypogammaglobulinemia both as an opposed response or laboratory IgG stage under 500mg/dl, after infusion occurred in 94% (267/285) of sufferers handled. Fifty-six % (161/285) of sufferers obtained intravenous immunoglobulin (IVIG) put up CARVYKTI ® for both an opposed response or prophylaxis.
Monitor immunoglobulin ranges after remedy with CARVYKTI ® and administer IVIG for IgG <400 mg/dL. Handle per native institutional pointers, together with an infection precautions and antibiotic or antiviral prophylaxis.
Use of Stay Vaccines: The protection of immunization with stay viral vaccines throughout or following CARVYKTI ® remedy has not been studied. Vaccination with stay virus vaccines will not be really helpful for no less than 6 weeks previous to the beginning of lymphodepleting chemotherapy, throughout CARVYKTI ® remedy, and till immune restoration following remedy with CARVYKTI ®.
HYPERSENSITIVITY REACTIONS occurred following remedy with CARVYKTI ®. Amongst sufferers receiving CARVYKTI ® within the CARTITUDE-1 & 4 research, hypersensitivity reactions occurred in 5% (13/285), all of which had been ‰¤ Grade 2. Manifestations of hypersensitivity reactions included flushing, chest discomfort, tachycardia, wheezing, tremor, burning sensation, non-cardiac chest ache, and pyrexia.
Critical hypersensitivity reactions, together with anaphylaxis, could also be because of the dimethyl sulfoxide (DMSO) in CARVYKTI ®. Sufferers must be rigorously monitored for two hours after infusion for indicators and signs of extreme response. Deal with promptly and handle sufferers appropriately in accordance with the severity of the hypersensitivity response.
SECONDARY MALIGNANCIES: Sufferers handled with CARVYKTI ® might develop secondary malignancies. Amongst sufferers receiving CARVYKTI ® within the CARTITUDE-1 & 4 research, myeloid neoplasms occurred in 5% (13/285) of sufferers (9 instances of myelodysplastic syndrome, 3 instances of acute myeloid leukemia, and 1 case of myelodysplastic syndrome adopted by acute myeloid leukemia). The median time to onset of myeloid neoplasms was 447 days (vary: 56 to 870 days) after remedy with CARVYKTI ®. Ten of those 13 sufferers died following the event of myeloid neoplasms; 2 of the 13 instances of myeloid neoplasm occurred after initiation of subsequent antimyeloma remedy. Instances of myelodysplastic syndrome and acute myeloid leukemia have additionally been reported within the post-marketing setting. T-cell malignancies have occurred following remedy of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies, together with CARVYKTI ®. Mature T-cell malignancies, together with CAR-positive tumors, might current as quickly as weeks following infusions and will embody deadly outcomes.
Monitor life-long for secondary malignancies. Within the occasion {that a} secondary malignancy happens, contact Janssen Biotech, Inc. at 1-800-526-7736 for reporting and to acquire directions on assortment of affected person samples.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES: Because of the potential for neurologic occasions, together with altered psychological standing, seizures, neurocognitive decline, or neuropathy, sufferers receiving CARVYKTI ® are in danger for altered or decreased consciousness or coordination within the 8 weeks following CARVYKTI ® infusion. Advise sufferers to chorus from driving and fascinating in hazardous occupations or actions, comparable to working heavy or probably harmful equipment throughout this preliminary interval, and within the occasion of recent onset of any neurologic toxicities.
ADVERSE REACTIONS
The most typical nonlaboratory opposed reactions (incidence higher than 20%) are pyrexia, cytokine launch syndrome, hypogammaglobulinemia, hypotension, musculoskeletal ache, fatigue, infections-pathogen unspecified, cough, chills, diarrhea, nausea, encephalopathy, decreased urge for food, higher respiratory tract an infection, headache, tachycardia, dizziness, dyspnea, edema, viral infections, coagulopathy, constipation, and vomiting. The most typical Grade 3 or 4 laboratory opposed reactions (incidence higher than or equal to 50%) embody lymphopenia, neutropenia, white blood cell decreased, thrombocytopenia, and anemia.
Please learn full Prescribing Data, together with Boxed Warning, for CARVYKTI ®.
ABOUT CARVYKTI ® (CILTACABTAGENE AUTOLEUCEL; CILTA-CEL)
Ciltacabtagene autoleucel is a BCMA-directed, genetically modified autologous T-cell immunotherapy, which entails reprogramming a affected person’s personal T-cells with a transgene encoding a chimeric antigen receptor (CAR) that identifies and eliminates cells that categorical BCMA. The cilta-cel CAR protein options two BCMA-targeting single area antibodies designed to confer excessive avidity in opposition to human BCMA. Upon binding to BCMA-expressing cells, the CAR promotes T-cell activation, enlargement, and elimination of goal cells.2
In December 2017, Legend Biotech entered into an unique worldwide license and collaboration settlement with Janssen Biotech, Inc. (Janssen), a Johnson & Johnson (NYSE:) firm, to develop and commercialize cilta-cel. In February 2022, cilta-cel was accredited by the U.S. Meals and Drug Administration (FDA) underneath the model identify CARVYKTI ® for the remedy of adults with relapsed or refractory a number of myeloma. In April 2024, cilta-cel was accredited for the second-line remedy of sufferers with relapsed/refractory myeloma who’ve obtained no less than one prior line of remedy together with a proteasome inhibitor, an immunomodulatory agent, and are refractory to lenalidomide.
In Might 2022, the European Fee (EC) granted conditional advertising authorization of CARVYKTI ® for the remedy of adults with relapsed or refractory a number of myeloma. In September 2022, Japan’s Ministry of Well being, Labour and Welfare (MHLW) accredited CARVYKTI ®. Cilta-cel was granted Breakthrough Remedy Designation within the U.S. in December 2019 and in China in August 2020. As well as, cilta-cel obtained a PRIority MEdicines (PRIME) designation from the European Fee in April 2019. Cilta-cel additionally obtained Orphan Drug Designation from the U.S. FDA in February 2019, from the European Fee in February 2020, and from the Prescription drugs and Medicinal Gadgets Company (PMDA) in Japan in June 2020. In March 2022, the European Medicines Company’s Committee for Orphan Medicinal Merchandise really helpful by consensus that the orphan designation for cilta-cel be maintained on the idea of medical information demonstrating improved and sustained full response charges following remedy.
ABOUT CARTITUDE-4
CARTITUDE-4 (NCT04181827) is an ongoing, worldwide, randomized, open-label Section 3 research evaluating the efficacy and security of cilta-cel versus pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) in grownup sufferers with relapsed or lenalidomide-refractory a number of myeloma who obtained one to 3 prior traces of remedy, together with a PI and an IMiD.3
ABOUT MULTIPLE MYELOMA
A number of myeloma is an incurable blood most cancers that begins within the bone marrow and is characterised by an extreme proliferation of plasma cells.4 In 2024, it’s estimated that greater than 35,000 individuals might be identified with a number of myeloma, and greater than 12,000 individuals will die from the illness within the U.S.5 Whereas some sufferers with a number of myeloma initially don’t have any signs, most sufferers are identified because of signs that may embody bone issues, low blood counts, calcium elevation, kidney issues or infections.6
ABOUT LEGEND BIOTECH
Legend Biotech is a worldwide biotechnology firm devoted to treating, and at some point curing, life-threatening illnesses. Headquartered in Somerset, New Jersey, we’re creating superior cell therapies throughout a various array of expertise platforms, together with autologous and allogeneic chimeric antigen receptor T-cell, gamma-delta T cell (gd T) and pure killer (NK) cell-based immunotherapy. From our three R&D websites all over the world, we apply these modern applied sciences to pursue the invention of cutting-edge therapeutics for sufferers worldwide.
Be taught extra at www.legendbiotech.com and comply with us on X (previously Twitter) and LinkedIn.
CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS
Statements on this press launch about future expectations, plans, and prospects, in addition to some other statements relating to issues that aren’t historic info, represent forward-looking statements throughout the which means of The Personal Securities Litigation Reform Act of 1995. These statements embody, however will not be restricted to, statements regarding Legend Biotech’s methods and targets; statements regarding CARVYKTI ®, together with Legend Biotech’s expectations for CARVYKTI ® and its therapeutic potential; statements associated to the potential outcomes from ongoing research within the CARTITUDE medical improvement program; and the potential advantages of Legend Biotech’s product candidates. The phrases anticipate, imagine, proceed, might, estimate, count on, intend, might, plan, potential, predict, challenge, ought to, goal, will, would and related expressions are supposed to establish forward-looking statements, though not all forward-looking statements comprise these figuring out phrases. Precise outcomes might differ materially from these indicated by such forward-looking statements because of varied vital elements. Legend Biotech’s expectations could possibly be affected by, amongst different issues, uncertainties concerned within the improvement of recent pharmaceutical merchandise; sudden medical trial outcomes, together with because of further evaluation of current medical information or sudden new medical information; sudden regulatory actions or delays, together with requests for added security and/or efficacy information or evaluation of information, or authorities regulation typically; sudden delays because of actions undertaken, or failures to behave, by our third social gathering companions; uncertainties arising from challenges to Legend Biotech’s patent or different proprietary mental property safety, together with the uncertainties concerned within the U.S. litigation course of; authorities, business, and normal product pricing and different political pressures; in addition to the opposite elements mentioned within the Threat Components part of Legend Biotech’s Annual Report on Kind 20-F filed with the Securities and Change Fee on March 19, 2024. Ought to a number of of those dangers or uncertainties materialize, or ought to underlying assumptions show incorrect, precise outcomes might differ materially from these described on this press launch as anticipated, believed, estimated or anticipated. Any forward-looking statements contained on this press launch converse solely as of the date of this press launch. Legend Biotech particularly disclaims any obligation to replace any forward-looking assertion, whether or not because of new data, future occasions or in any other case
¡Maria-Victoria Mateos, M.D., Ph.D., Guide Doctor within the Hematology Division and Affiliate Professor of Medication on the College of Salamanca, Spain. has offered consulting, advisory, and talking providers to Legend Biotech; has not been paid for any media work.
INVESTOR CONTACT:
Jessie Yeung
Tel: (732) 956-8271
jessie.yeung@legendbiotech.com
PRESS CONTACT:
Mary Ann Ondish
Tel: (914) 552-4625
media@legendbiotech.com
REFERENCES
1 Mateos, et al. Total Survival (OS) With Ciltacabtagene Autoleucel (Cilta-cel) Versus Normal of Care (SoC) in Lenalidomide (Len)-Refractory A number of Myeloma (MM): Section 3 CARTITUDE-4 Research Replace. Worldwide Myeloma Society 2024 Annual Assembly. September 2024.
2 CARVYKTI™ Prescribing Data. Horsham, PA: Janssen Biotech, Inc.
3 ClinicalTrials.Gov. A Research Evaluating JNJ-68284528, a CAR-T Remedy Directed In opposition to B-cell Maturation Antigen (BCMA), Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd) in Contributors With Relapsed and Lenalidomide-Refractory A number of Myeloma (CARTITUDE-4). https://www.clinicaltrials.gov/research/NCT04181827. Accessed March 2024.
4 American Most cancers Society. What’s A number of Myeloma?. Accessible at: https://www.most cancers.org/most cancers/varieties/multiple-myeloma/about/what-is-multiple-myeloma.html. Accessed March 2024.
5 American Most cancers Society. Key Statistics About A number of Myeloma. Accessible at: https://www.most cancers.org/most cancers/varieties/multiple-myeloma/about/key-statistics.html. Accessed March 2024
6 American Most cancers Society. A number of myeloma: early detection, analysis, and staging. Accessible at: https://www.most cancers.org/content material/dam/CRC/PDF/Public/8740.00.pdf. Accessed March 2023.
