“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 recent 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 reveal 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 customary regimens for these sufferers.”

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

Outcomes for the important thing secondary endpoint of general response price additionally met statistical significance with nearly all of sufferers (71%) handled with Abecma attaining a response, and 39% attaining an entire response or stringent full response. Compared, lower than half of sufferers (41%) who acquired customary regimens achieved a response, with 5% experiencing an entire response or stringent full response (p Abecma had been sturdy with a median period of 14.8 months (95% CI: 12.0-18.6) in contrast with 9.7 months (95% CI: 5.4-16.3) for normal regimens. Scientific profit with Abecma was persistently 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 customary therapy method that gives sturdy responses,” mentioned Sergio Giralt, M.D., Division of Hematologic Malignancies, Memorial Sloan Kettering Most cancers Middle. “On this research, we’re seeing efficacy amongst a inhabitants with traditionally difficult-to-treat illness, with a major 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 turn out to be a regular 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 alerts, 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 period 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 period of neurotoxicity was 2 days (vary: 1-37).

“The KarMMa-3 research is the primary with a BCMA-directed CAR T remedy to reveal superiority versus customary 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 information revealed to construct on the compelling efficacy profile of Abecma demonstrating important enchancment in progression-free survival and we look ahead to working with regulatory authorities to make Abecma obtainable to extra myeloma sufferers who may benefit from this essential therapy choice.”

Bristol Myers Squibb and 2seventy bio intend to incorporate these information 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 accredited 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 Info part under, together with Boxed WARNINGS for Abecma concerning CRS, neurologic toxicities, Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome and Extended Cytopenia. Abecma can also be accredited 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 Middle disclosures: Dr. Giralt and Memorial Sloan Kettering Most cancers Middle 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 customary regimens in sufferers with relapsed and refractory a number of myeloma who’ve acquired two to 4 prior strains of therapy, together with an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody, and had been refractory to the final therapy routine. Sufferers had been randomized to obtain Abecma or customary regimens that consisted of combos 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 based mostly 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 loss of life because of any trigger, whichever happens first. Key secondary endpoints embody general response price and general 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-Growth, Co-Promotion, and Revenue Share Settlement between Bristol Myers Squibb and 2seventy bio.

The businesses’ broad medical growth program for Abecma contains 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 Info

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 accessible solely by a restricted program underneath a Threat Analysis and Mitigation Technique (REMS) referred to 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 greater 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 period of CRS was 7 days (vary: 1 – 63 days). The commonest manifestations included pyrexia, hypotension, tachycardia, chills, hypoxia, fatigue, and headache. Grade 3 or greater occasions that could 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.

Establish CRS based mostly 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 acquired tocilizumab (single dose: 35%; greater than 1 dose: 18%). General, 15% (19/127) of sufferers acquired at the very least 1 dose of corticosteroids for therapy of CRS. All sufferers that acquired corticosteroids for CRS acquired tocilizumab. Make sure that a minimal of two doses of tocilizumab can be found previous to infusion of ABECMA.

Monitor sufferers at the very least every 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 instant 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 loss of life. 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 period 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. Probably the most often 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 every 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 needs to be managed with supportive care and/or corticosteroids as wanted.

Counsel sufferers to hunt instant 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 price if not acknowledged early and handled. Therapy of HLH/MAS needs to be administered per institutional pointers.

ABECMA REMS: Because of the danger of CRS and neurologic toxicities, ABECMA is accessible solely by a restricted program underneath a Threat Analysis and Mitigation Technique (REMS) referred to as the ABECMA REMS. Additional info is accessible 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 because 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 line with customary institutional pointers.

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 loss of life has occurred following ABECMA administration. Monitor and deal with for CMV reactivation in accordance with medical pointers. Hepatitis B virus (HBV) reactivation, in some circumstances leading to fulminant hepatitis, hepatic failure, and loss of life, can happen in sufferers handled with medicine directed in opposition to plasma cells. Carry out screening for CMV, HBV, hepatitis C virus (HCV), and human immunodeficiency virus (HIV) in accordance with medical pointers 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 because of extended cytopenia. Two of the three sufferers died from issues 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 adversarial occasion in 21% (27/127) of sufferers; laboratory IgG ranges fell under 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 just 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 fascinating in hazardous occupations or actions, corresponding to working heavy or probably harmful equipment, throughout this preliminary interval.

Adversarial Reactions: The commonest nonlaboratory adversarial 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 Info , 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—remodeling sufferers’ lives by science. The purpose of the corporate’s most cancers analysis is to ship medicines that supply every affected person a greater, more healthy life and to make treatment a chance. 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 personalised medication, and thru progressive digital platforms, are turning information 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 components of a affected person’s life, and Bristol Myers Squibb is dedicated to taking actions to deal with all points of care, from analysis to survivorship. As a result of as a frontrunner in most cancers care, Bristol Myers Squibb is working to empower all folks with most cancers to have a greater future.

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

About Bristol Myers Squibb

Bristol Myers Squibb is a worldwide 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 observe us on LinkedIn , Twitter , YouTube , Fb and Instagram .

About 2seventy bio

Our identify, 2seventy bio, displays why we do what we do – TIME. Most cancers rips time away, and our purpose is to work on the most pace of translating human thought into motion – 270 miles per hour – to offer the folks we serve extra time. We’re constructing the main immuno-oncology cell remedy firm, centered on discovering and creating new therapies that actually disrupt the most cancers therapy panorama With a deep understanding of the human physique’s immune response to tumor cells and easy methods to translate cell therapies into follow, we’re making use of this information 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 growth is targeted on delivering therapies which are designed with the purpose to “assume” smarter and sooner than the illness. Importantly, we stay centered on undertaking these objectives by staying real and genuine to our “why” and protecting our folks and tradition high of thoughts day-after-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-Trying Statements

This press launch incorporates “forward-looking statements” inside the that means of the Personal Securities Litigation Reform Act of 1995 concerning, amongst different issues, the analysis, growth and commercialization of pharmaceutical merchandise. All statements that aren’t statements of historic info are, or could also be deemed to be, forward-looking statements. Such forward-looking statements are based mostly on present expectations and projections about our future monetary outcomes, objectives, plans and targets and contain inherent dangers, assumptions and uncertainties, together with inner or exterior elements that might delay, divert or change any of them within the subsequent a number of years, which are troublesome 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 is probably not according to the outcomes so far, that Abecma ^® (idecabtagene vicleucel), might not obtain regulatory approval for the extra indication described on this launch within the at the moment anticipated timeline or in any respect, that any advertising approvals, if granted, might have important limitations on their use, and, if accredited, whether or not such product candidate for such further indication described on this launch shall be commercially profitable . No forward-looking assertion might be assured. Ahead-looking statements on this press launch needs to be evaluated along with the various dangers and uncertainties that have an effect on Bristol Myers Squibb’s enterprise and market, notably these recognized within the cautionary assertion and danger elements dialogue in Bristol Myers Squibb’s Annual Report on Kind 10-Ok for the yr ended December 31, 2021, as up to date by our subsequent Quarterly Reviews on Kind 10-Q, Present Reviews on Kind 8-Ok and different filings with the Securities and Trade 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 regulation, Bristol Myers Squibb undertakes no obligation to publicly replace or revise any forward-looking assertion, whether or not on account of new info, future occasions, modified circumstances or in any other case.

2seventy bio Cautionary Notice Concerning Ahead-Trying Statements

This press launch incorporates “forward-looking statements” inside the that means of the Personal Securities Litigation Reform Act of 1995 concerning, amongst different issues, the analysis, growth and commercialization of Abecma ^® (idecabtagene vicleucel). All statements that aren’t statements of historic info are, or could also be deemed to be, forward-looking statements. Such forward-looking statements are based mostly 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 inner or exterior elements that might delay, divert or change any of them within the subsequent a number of years, which are troublesome 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 chance that Abecma might not obtain FDA approval for the indication described on this launch within the at the moment anticipated timeline or in any respect, that any advertising approvals, if granted, might have important limitations on their use, that Abecma is probably not commercially profitable and that collaboration with Bristol Myers Squibb might not proceed or achieve success. No forward-looking assertion might be assured. Ahead-looking statements on this press launch needs to be evaluated along with the various dangers and uncertainties that have an effect on 2seventy bio’s enterprise, notably these recognized within the danger elements dialogue in 2seventy bio’s Annual Report on Kind 10-Ok, as up to date by our subsequent Quarterly Reviews on Kind 10-Q, Present Reviews on Kind 8-Ok and different filings with the Securities and Trade 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 regulation, 2seventy bio undertakes no obligation to publicly replace or revise any forward-looking assertion, whether or not on account of new info, future occasions, modified circumstances or in any other case.

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