“In earlier strains of therapy for a number of myeloma, regimens consisting of immunomodulatory brokers, proteasome inhibitors, and anti-CD38 monoclonal antibodies are sometimes used to assist handle the illness. This shift within the therapy paradigm leaves many sufferers who’re triple-class uncovered with relapsed and refractory illness and in want of latest therapy choices sooner,” mentioned Paula Rodriguez-Otero, M.D., Ph.D., Division of Hematology, Clinica Universidad de Navarra, Pamplona, Spain. “Outcomes from the KarMMa-3 research with Abecma clearly exhibit the advantage of earlier use of a CAR T cell remedy in offering the longest progression-free survival for sufferers with relapsed and refractory a number of myeloma in comparison with present normal regimens for these sufferers.”

“With Abecma, our first-in-class anti-BCMA CAR T cell remedy, we sought to ship a customized remedy that gives sturdy outcomes with a single infusion to advance the a number of myeloma therapy paradigm for sufferers,” mentioned Anne Kerber, senior vice chairman, Cell Remedy Improvement, Bristol Myers Squibb. “This represents the third New England Journal of Drugs publication for Abecma, displaying the clear medical advantage of utilizing Abecma throughout strains of remedy for sufferers with triple-class uncovered relapsed and refractory a number of myeloma to supply the most effective probability for lasting illness management.”

Outcomes for the important thing secondary endpoint of total response charge additionally met statistical significance with the vast majority of sufferers (71%) handled with Abecma reaching a response, and 39% reaching a whole response or stringent full response. Compared, lower than half of sufferers (41%) who obtained normal regimens achieved a response, with 5% experiencing a whole response or stringent full response (p Abecma have been sturdy with a median length of 14.8 months (95% CI: 12.0-18.6) in contrast with 9.7 months (95% CI: 5.4-16.3) for traditional regimens. Scientific profit with Abecma was constantly noticed throughout difficult-to-treat subgroups.

“For relapsing triple-class uncovered a number of myeloma sufferers, median progression-free survival is simply 4.6 months and there’s no established normal therapy strategy that gives sturdy responses,” mentioned Sergio Giralt, M.D., Division of Hematologic Malignancies, Memorial Sloan Kettering Most cancers Heart. “On this research, we’re seeing efficacy amongst a inhabitants with traditionally difficult-to-treat illness, with a big enchancment in progression-free survival and deep and lasting responses. These outcomes from KarMMa-3 introduce the potential for this anti-BCMA CAR T cell remedy to change into an ordinary of care earlier within the therapy course for relapsed and refractory a number of myeloma.”

Abecma exhibited a constant and usually predictable security profile, together with no new security indicators, with principally low-grade occurrences of cytokine launch syndrome (CRS) and neurotoxicity. In sufferers handled with Abecma, 88% skilled any grade CRS, with Grade 3/4 occasions occurring in 4% of sufferers. Two sufferers (1%) skilled a Grade 5 CRS occasion. Median time to onset of CRS was 1 day (vary: 1-14) and median length of CRS was 3.5 days (vary: 1-51). Any grade neurotoxicity occurred in 15% of sufferers, with Grade 3/4 neurotoxicity occurring in 3% of sufferers, and no Grade 5 occasions reported. Median time to onset of neurotoxicity was 3 days (vary: 1-317) and median length of neurotoxicity was 2 days (vary: 1-37).

“The KarMMa-3 research is the primary with a BCMA-directed CAR T remedy to exhibit superiority versus normal regimens for sufferers with relapsed and refractory a number of myeloma, illustrating the potential of Abecma to alter the usual of care of triple-class uncovered a number of myeloma in early strains,” mentioned Steve Bernstein, M.D., chief medical officer, 2seventy bio. “We’re happy to current and have these knowledge revealed to construct on the compelling efficacy profile of Abecma demonstrating vital enchancment in progression-free survival and we sit up for working with regulatory authorities to make Abecma accessible to extra myeloma sufferers who may benefit from this vital therapy choice.”

Bristol Myers Squibb and 2seventy bio intend to incorporate these knowledge in a deliberate supplemental Biologics License Software submission to the U.S. Meals and Drug Administration (FDA) in 2023. Abecma is the first-in-class B-cell maturation antigen (BCMA)-directed CAR T cell immunotherapy accepted by the FDA for the therapy of grownup sufferers with relapsed or refractory a number of myeloma after 4 or extra prior strains of remedy, together with an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. Please see the Essential Security Data part beneath, together with Boxed WARNINGS for Abecma relating to CRS, neurologic toxicities, Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome and Extended Cytopenia. Abecma can also be accepted within the European Union, Switzerland, Japan, Canada, the UK and Israel for grownup sufferers with triple-class uncovered relapsed or refractory a number of myeloma after three to 4 or extra prior strains of remedy.

Memorial Sloan Kettering Most cancers Heart disclosures: Dr. Giralt and Memorial Sloan Kettering Most cancers Heart have monetary pursuits related to the analysis described on this launch.

About KarMMa-3

KarMMa-3 (NCT03651128) is a pivotal, Section 3, open-label, international, randomized, managed trial evaluating Abecma in comparison with normal regimens in sufferers with relapsed and refractory a number of myeloma who’ve obtained two to 4 prior strains of therapy, together with an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody, and have been refractory to the final therapy routine. Sufferers have been randomized to obtain Abecma or normal regimens that consisted of mixtures that included daratumumab, pomalidomide, and dexamethasone (DPd), daratumumab, bortezomib, and dexamethasone (DVd), ixazomib, lenalidomide, and dexamethasone (IRd), carfilzomib and dexamethasone (Kd) or elotuzumab, pomalidomide and dexamethasone (EPd) chosen primarily based on their most up-to-date therapy routine and investigator discretion. The first endpoint evaluated on this research is progression-free survival, outlined as time from randomization to the primary documentation of progressive illness or dying on account of any trigger, whichever happens first. Key secondary endpoints embody total response charge and total survival.

About Abecma

Abecma acknowledges and binds to BCMA on the floor of a number of myeloma cells resulting in CAR T cell proliferation, cytokine secretion, and subsequent cytolytic killing of BCMA-expressing cells. Abecma is being collectively developed and commercialized within the U.S. as a part of a Co-Improvement, Co-Promotion, and Revenue Share Settlement between Bristol Myers Squibb and 2seventy bio.

The businesses’ broad medical improvement program for Abecma consists of medical research (KarMMa-2, KarMMa-3, KarMMa-9) in earlier strains of therapy for sufferers with a number of myeloma. For extra info go to clinicaltrials.gov .

Essential Security Data

BOXED WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, AND PROLONGED CYTOPENIA

• Cytokine Launch Syndrome (CRS), together with deadly or life-threatening reactions, occurred in sufferers following therapy with ABECMA. Don’t administer ABECMA to sufferers with energetic an infection or inflammatory issues. Deal with extreme or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
• Neurologic Toxicities, which can be extreme or life-threatening, occurred following therapy with ABECMA, together with concurrently with CRS, after CRS decision, or within the absence of CRS. Monitor for neurologic occasions after therapy with ABECMA. Present supportive care and/or corticosteroids as wanted.
• Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS) together with deadly and life-threatening reactions, occurred in sufferers following therapy with ABECMA. HLH/MAS can happen with CRS or neurologic toxicities.
• Extended Cytopenia with bleeding and an infection, together with deadly outcomes following stem cell transplantation for hematopoietic restoration, occurred following therapy with ABECMA.
• ABECMA is obtainable solely via a restricted program below a Danger Analysis and Mitigation Technique (REMS) known as the ABECMA REMS

WARNINGS AND PRECAUTIONS:

Cytokine Launch Syndrome (CRS): CRS, together with deadly or life-threatening reactions, occurred following therapy with ABECMA in 85% (108/127) of sufferers. Grade 3 or increased CRS occurred in 9% (12/127) of sufferers, with Grade 5 CRS reported in a single (0.8%) affected person. The median time to onset of CRS, any grade, was 1 day (vary: 1 – 23 days) and the median length of CRS was 7 days (vary: 1 – 63 days). The commonest manifestations included pyrexia, hypotension, tachycardia, chills, hypoxia, fatigue, and headache. Grade 3 or increased occasions which may be related to CRS embody hypotension, hypoxia, hyperbilirubinemia, hypofibrinogenemia, acute respiratory misery syndrome (ARDS), atrial fibrillation, hepatocellular harm, metabolic acidosis, pulmonary edema, a number of organ dysfunction syndrome, and HLH/MAS.

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. In sufferers with progressive signs of CRS or refractory CRS regardless of therapy, consider for proof of HLH/MAS.

Fifty 4 p.c (68/127) of sufferers obtained tocilizumab (single dose: 35%; greater than 1 dose: 18%). General, 15% (19/127) of sufferers obtained at the very least 1 dose of corticosteroids for therapy of CRS. All sufferers that obtained corticosteroids for CRS obtained tocilizumab. Be sure that a minimal of two doses of tocilizumab can be found previous to infusion of ABECMA.

Monitor sufferers at the very least day by day for 7 days following ABECMA infusion on the REMS-certified healthcare facility for indicators or signs of CRS and monitor sufferers for indicators or signs of CRS for at the very least 4 weeks after ABECMA infusion. On the first signal of CRS, institute therapy with supportive care, tocilizumab and/or corticosteroids as indicated.

Counsel sufferers to hunt fast medical consideration ought to indicators or signs of CRS happen at any time.

Neurologic Toxicities: Neurologic toxicities, which can be extreme or life-threatening, occurred following therapy with ABECMA in 28% (36/127) of sufferers receiving ABECMA, together with Grade 3 in 4% (5/127) of sufferers. One affected person had ongoing Grade 2 neurotoxicity on the time of dying. Two sufferers had ongoing Grade 1 tremor on the time of information cutoff. The median time to onset of neurotoxicity was 2 days (vary: 1 – 42 days). CAR T cell-associated neurotoxicity resolved in 92% (33/36) of sufferers with a median time to decision of 5 days (vary: 1 – 61 days). The median length of neurotoxicity was 6 days (vary: 1 – 578) in all sufferers together with 3 sufferers with ongoing neurotoxicity. Thirty-four sufferers with neurotoxicity had CRS with onset in 3 sufferers earlier than, 29 sufferers throughout, and a pair of sufferers after CRS. Essentially the most continuously reported manifestations of CAR T cell-associated neurotoxicity embody encephalopathy, tremor, aphasia, and delirium. Grade 4 neurotoxicity and cerebral edema in 1 affected person, Grade 3 myelitis, and Grade 3 parkinsonism have been reported with ABECMA in one other research in a number of myeloma.

Monitor sufferers at the very least day by day for 7 days following ABECMA infusion on the REMS-certified healthcare facility for indicators or signs of neurologic toxicities and monitor sufferers for indicators or signs of neurologic toxicities for at the very least 4 weeks after ABECMA infusion and deal with promptly. Rule out different causes of neurologic signs. Neurologic toxicity ought to be managed with supportive care and/or corticosteroids as wanted.

Counsel sufferers to hunt fast medical consideration ought to indicators or signs happen at any time.

Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS): HLH/MAS occurred in 4% (5/127) of sufferers receiving ABECMA. One affected person developed deadly multi-organ HLH/MAS with CRS and one other affected person developed deadly bronchopulmonary aspergillosis with contributory HLH/MAS. Three circumstances of Grade 2 HLH/MAS resolved. All occasions of HLH/MAS had onset inside 10 days of receiving ABECMA with a median onset of seven days (vary: 4 – 9 days) and occurred within the setting of ongoing or worsening CRS. Two sufferers with HLH/MAS had overlapping neurotoxicity. The manifestations of HLH/MAS embody hypotension, hypoxia, a number of organ dysfunction, renal dysfunction, and cytopenia. HLH/MAS is a probably life-threatening situation with a excessive mortality charge if not acknowledged early and handled. Remedy of HLH/MAS ought to be administered per institutional tips.

ABECMA REMS: Because of the threat of CRS and neurologic toxicities, ABECMA is obtainable solely via a restricted program below a Danger Analysis and Mitigation Technique (REMS) known as the ABECMA REMS. Additional info is obtainable at www.AbecmaREMS.com or 1-888-423-5436.

Hypersensitivity Reactions: Allergic reactions might happen with the infusion of ABECMA. Critical hypersensitivity reactions, together with anaphylaxis, could also be on account of dimethyl sulfoxide (DMSO) in ABECMA.

Infections: ABECMA shouldn’t be administered to sufferers with energetic infections or inflammatory issues. Extreme, life-threatening, or deadly infections occurred in sufferers after ABECMA infusion. Infections (all grades) occurred in 70% of sufferers. Grade 3 or 4 infections occurred in 23% of sufferers. General, 4 sufferers had Grade 5 infections (3%); 2 sufferers (1.6%) had Grade 5 occasions of pneumonia, 1 affected person (0.8%) had Grade 5 bronchopulmonary aspergillosis, and 1 affected person (0.8%) had cytomegalovirus (CMV) pneumonia related to Pneumocystis jirovecii. Monitor sufferers for indicators and signs of an infection earlier than and after ABECMA infusion and deal with appropriately. Administer prophylactic, pre-emptive, and/or therapeutic antimicrobials in response to normal institutional tips.

Febrile neutropenia was noticed in 16% (20/127) of sufferers after ABECMA 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.

Viral Reactivation : CMV an infection leading to pneumonia and dying has occurred following ABECMA administration. Monitor and deal with for CMV reactivation in accordance with medical tips. Hepatitis B virus (HBV) reactivation, in some circumstances leading to fulminant hepatitis, hepatic failure, and dying, can happen in sufferers handled with medicine directed towards plasma cells. Carry out screening for CMV, HBV, hepatitis C virus (HCV), and human immunodeficiency virus (HIV) in accordance with medical tips earlier than assortment of cells for manufacturing.

Extended Cytopenias: Within the medical research, 41% of sufferers (52/127) skilled extended Grade 3 or 4 neutropenia and 49% (62/127) skilled extended Grade 3 or 4 thrombocytopenia that had not resolved by Month 1 following ABECMA infusion. In 83% (43/52) of sufferers who recovered from Grade 3 or 4 neutropenia after Month 1, the median time to restoration from ABECMA infusion was 1.9 months. In 65% (40/62) of sufferers who recovered from Grade 3 or 4 thrombocytopenia, the median time to restoration was 2.1 months.

Three sufferers underwent stem cell remedy for hematopoietic reconstitution on account of extended cytopenia. Two of the three sufferers died from problems of extended cytopenia. Monitor blood counts previous to and after ABECMA infusion. Handle cytopenia with myeloid progress issue and blood product transfusion help.

Hypogammaglobulinemia: Hypogammaglobulinemia was reported as an antagonistic occasion in 21% (27/127) of sufferers; laboratory IgG ranges fell beneath 500 mg/dl after infusion in 25% (32/127) of sufferers handled with ABECMA.

Monitor immunoglobulin ranges after therapy with ABECMA and administer IVIG for IgG

The protection of immunization with dwell viral vaccines throughout or after ABECMA therapy has not been studied. Vaccination with dwell virus vaccines isn’t beneficial for at the very least 6 weeks previous to the beginning of lymphodepleting chemotherapy, throughout ABECMA therapy, and till immune restoration following therapy with ABECMA.

Secondary Malignancies: Sufferers handled with ABECMA might develop secondary malignancies. Monitor life-long for secondary malignancies. If a secondary malignancy happens, contact Bristol-Myers Squibb at 1-888-805-4555 to acquire directions on affected person samples to gather for testing of secondary malignancy of T cell origin.

Results on Skill to Drive and Function Equipment: Because of the potential for neurologic occasions, sufferers receiving ABECMA are in danger for altered or decreased consciousness or coordination within the 8 weeks following ABECMA infusion. Advise sufferers to chorus from driving and interesting in hazardous occupations or actions, similar to working heavy or probably harmful equipment, throughout this preliminary interval.

Opposed Reactions: The commonest nonlaboratory antagonistic reactions embody CRS, infections – pathogen unspecified, fatigue, musculoskeletal ache, hypogammaglobulinemia, diarrhea, higher respiratory tract an infection, nausea, viral infections, encephalopathy, edema, pyrexia, cough, headache, and decreased urge for food.

Please see full Prescribing Data , together with Boxed WARNINGS and Medicine Information .

Bristol Myers Squibb: Making a Higher Future for Folks with Most cancers

Bristol Myers Squibb is impressed by a single imaginative and prescient—reworking sufferers’ lives via science. The aim of the corporate’s most cancers analysis is to ship medicines that provide every affected person a greater, more healthy life and to make treatment a risk. Constructing on a legacy throughout a broad vary of cancers which have modified survival expectations for a lot of, Bristol Myers Squibb researchers are exploring new frontiers in customized medication, and thru progressive digital platforms, are turning knowledge into insights that sharpen their focus. Deep scientific experience, cutting-edge capabilities and discovery platforms allow the corporate to have a look at most cancers from each angle. Most cancers can have a relentless grasp on many elements of a affected person’s life, and Bristol Myers Squibb is dedicated to taking actions to handle all elements of care, from prognosis to survivorship. As a result of as a frontrunner in most cancers care, Bristol Myers Squibb is working to empower all individuals with most cancers to have a greater future.

Be taught extra in regards to the science behind cell remedy and ongoing analysis at Bristol Myers Squibb right here .

About Bristol Myers Squibb

Bristol Myers Squibb is a world biopharmaceutical firm whose mission is to find, develop and ship progressive medicines that assist sufferers prevail over critical illnesses. For extra details about Bristol Myers Squibb, go to us at BMS.com or comply with us on LinkedIn , Twitter , YouTube , Fb and Instagram .

About 2seventy bio

Our title, 2seventy bio, displays why we do what we do – TIME. Most cancers rips time away, and our aim is to work on the most velocity of translating human thought into motion – 270 miles per hour – to offer the individuals we serve extra time. We’re constructing the main immuno-oncology cell remedy firm, targeted on discovering and growing new therapies that really disrupt the most cancers therapy panorama With a deep understanding of the human physique’s immune response to tumor cells and how one can translate cell therapies into follow, we’re making use of this data to ship subsequent era mobile therapies that target a broad vary of hematologic malignancies, together with the primary FDA-approved CAR T cell remedy for a number of myeloma, in addition to strong tumors. Our analysis and improvement is targeted on delivering therapies which can be designed with the aim to “assume” smarter and quicker than the illness. Importantly, we stay targeted on engaging in these objectives by staying real and genuine to our “why” and maintaining our individuals and tradition prime of thoughts day by day.

For extra info, go to www.2seventybio.com .

Observe 2seventy bio on social media: Twitter and LinkedIn .

2seventy bio is a trademark of 2seventy bio, Inc.

Bristol Myers Squibb Cautionary Assertion Concerning Ahead-Wanting Statements

This press launch accommodates “forward-looking statements” throughout the which means of the Personal Securities Litigation Reform Act of 1995 relating to, amongst different issues, the analysis, improvement and commercialization of pharmaceutical merchandise. All statements that aren’t statements of historic details are, or could also be deemed to be, forward-looking statements. Such forward-looking statements are primarily based on present expectations and projections about our future monetary outcomes, objectives, plans and targets and contain inherent dangers, assumptions and uncertainties, together with inside or exterior elements that might delay, divert or change any of them within the subsequent a number of years, which can be tough to foretell, could also be past our management and will trigger our future monetary outcomes, objectives, plans and targets to vary materially from these expressed in, or implied by, the statements. These dangers, assumptions, uncertainties and different elements embody, amongst others, that future research outcomes will not be in step with the outcomes thus far, that Abecma ^® (idecabtagene vicleucel), might not obtain regulatory approval for the extra indication described on this launch within the presently anticipated timeline or in any respect, that any advertising and marketing approvals, if granted, might have vital limitations on their use, and, if accepted, whether or not such product candidate for such extra indication described on this launch can be commercially profitable . No forward-looking assertion may be assured. Ahead-looking statements on this press launch ought to be evaluated along with the numerous dangers and uncertainties that have an effect on Bristol Myers Squibb’s enterprise and market, significantly these recognized within the cautionary assertion and threat elements dialogue in Bristol Myers Squibb’s Annual Report on Type 10-Okay for the 12 months ended December 31, 2021, as up to date by our subsequent Quarterly Stories on Type 10-Q, Present Stories on Type 8-Okay and different filings with the Securities and Change Fee. The forward-looking statements included on this doc are made solely as of the date of this doc and besides as in any other case required by relevant legislation, Bristol Myers Squibb undertakes no obligation to publicly replace or revise any forward-looking assertion, whether or not because of new info, future occasions, modified circumstances or in any other case.

2seventy bio Cautionary Be aware Concerning Ahead-Wanting Statements

This press launch accommodates “forward-looking statements” throughout the which means of the Personal Securities Litigation Reform Act of 1995 relating to, amongst different issues, the analysis, improvement and commercialization of Abecma ^® (idecabtagene vicleucel). All statements that aren’t statements of historic details are, or could also be deemed to be, forward-looking statements. Such forward-looking statements are primarily based on historic efficiency and present expectations and projections about our future monetary outcomes, objectives, plans and targets and contain inherent dangers, assumptions and uncertainties, together with inside or exterior elements that might delay, divert or change any of them within the subsequent a number of years, which can be tough to foretell, could also be past our management and will trigger our future monetary outcomes, objectives, plans and targets to vary materially from these expressed in, or implied by, the statements. These dangers, assumptions, uncertainties and different elements embody, amongst others, the likelihood that Abecma might not obtain FDA approval for the indication described on this launch within the presently anticipated timeline or in any respect, that any advertising and marketing approvals, if granted, might have vital limitations on their use, that Abecma will not be commercially profitable and that collaboration with Bristol Myers Squibb might not proceed or achieve success. No forward-looking assertion may be assured. Ahead-looking statements on this press launch ought to be evaluated along with the numerous dangers and uncertainties that have an effect on 2seventy bio’s enterprise, significantly these recognized within the threat elements dialogue in 2seventy bio’s Annual Report on Type 10-Okay, as up to date by our subsequent Quarterly Stories on Type 10-Q, Present Stories on Type 8-Okay and different filings with the Securities and Change Fee. The forward-looking statements included on this doc are made solely as of the date of this doc and besides as in any other case required by relevant legislation, 2seventy bio undertakes no obligation to publicly replace or revise any forward-looking assertion, whether or not because of new info, future occasions, modified circumstances or in any other case.

Hyperlinks are supplied as a comfort and for informational functions solely. Neither Bristol Myers Squibb nor 2seventy bio bears duty for the safety or content material of exterior web sites or web sites exterior of their respective management.

corporatefinancial-news

View supply model on businesswire.com: https://www.businesswire.com/information/dwelling/20230209005647/en/

Bristol Myers Squibb

Media Inquiries:
media@bms.com

Kimberly Whitefield
kimberly.whitefield@bms.com

Traders:
investor.relations@bms.com

2seventy bio

Media:
Jenn Snyder
617-448-0281
jenn.snyder@2seventybio.com

Traders:
Elizabeth Pingpank
860-463-0469
elizabeth.pingpank@2seventybio.com