Bristol Myers Squibb’s CAR T Cell Remedy Breyanzi Authorised by the U.S. Meals and Drug Administration for Relapsed or Refractory Follicular Lymphoma

95.7% of sufferers responded to Breyanzi within the TRANSCEND FL trial

Breyanzi offered sustained medical profit with median period of response not reached and the bulk (77.1%) of responders in ongoing response at 18 months

Breyanzi is a customized remedy with a differentiated profile, providing sturdy responses and a constant security profile throughout trials

PRINCETON, N.J.–(BUSINESS WIRE)–Bristol Myers Squibb (NYSE: BMY) in the present day introduced the U.S. Meals and Drug Administration (FDA) has granted accelerated approval for Breyanzi ® (lisocabtagene maraleucel; liso-cel), a CD19-directed chimeric antigen receptor (CAR) T cell remedy, for the remedy of grownup sufferers with relapsed or refractory follicular lymphoma (FL) who’ve obtained two or extra prior traces of systemic remedy. This indication is accredited beneath accelerated approval primarily based on response fee and period of response. Continued approval for this indication could also be contingent upon verification and outline of medical profit in confirmatory trial(s). Breyanzi can also be now included within the Nationwide Complete Most cancers Community (NCCN ®) Medical Observe Tips in Oncology (NCCN Tips ®) for B-cell Lymphomas as a Class 2A suggestion for third-line and subsequent remedy for relapsed or refractory FL.

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In relapsed or refractory FL, Breyanzi is delivered as a one-time infusion with a single dose containing 90 to 110 x 106 CAR-positive viable T cells. Please see the Necessary Security Data part beneath, together with Boxed WARNINGS for Breyanzi concerning Cytokine Launch Syndrome (CRS), Neurologic Toxicities, and Secondary Hematological Malignancies.

Breyanzi is a cornerstone of our cell remedy portfolio, offering a differentiated profile throughout a wide selection of B-cell malignancies, stated Bryan Campbell, senior vp, Head of Business, Cell Remedy, Bristol Myers Squibb. Immediately’s approval of Breyanzi for relapsed or refractory FL offers an choice with potential for lasting remission in a one-time infusion and a security profile that permits for administration and monitoring in each the inpatient and outpatient setting in an growing variety of licensed remedy facilities within the U.S.

Traditionally, FL has been thought-about an incurable illness, and sufferers incessantly relapse following front-line remedy, with prognosis worsening after every subsequent relapse. Regardless of advances in remedy, there stays an unmet want for extra choices that supply treatment-free intervals with sturdy, full responses.

The Part 2 TRANSCEND FL research included the most important main evaluation set of sufferers with relapsed or refractory FL of a medical trial evaluating a CAR T cell remedy on this affected person inhabitants. Based mostly on the U.S. Prescribing Data (USPI), in sufferers handled with Breyanzi within the third-line plus setting and included within the main efficacy evaluation set (n=94), the general response fee (ORR) was 95.7% (95% CI: 89.5-98.8). ORR was outlined as the share of sufferers attaining a partial or full response per Lugano standards as assessed by an Unbiased Overview Committee (IRC). The whole response (CR) fee was 73.4% (95% CI: 63.3-82.0) and required a destructive bone marrow biopsy for affirmation. Responses have been speedy and sturdy with a median time to response of 1 month (vary: 0.6-3.3) and median period of response (DOR) not reached (95% CI: 18.04-NR), with 80.9% of responders remaining in response at 12 months, and 77.1% of responders remaining in response at 18 months. Outcomes from the first evaluation of TRANSCEND FL offered on the 2023 Worldwide Convention on Malignant Lymphoma confirmed an ORR of 97% (95% CI: 91.6-99.4; one-sided p

Within the remedy of relapsed or refractory follicular lymphoma, sufferers typically cycle via remedies with usually shorter responses with every new line of remedy. Those that have skilled early illness development have notably poor prognosis, stated M. Lia Palomba, M.D., TRANSCEND investigator and lymphoma and cell remedy specialist, Memorial Sloan Kettering Most cancers Middle. The FDA approval of liso-cel for sufferers with relapsed or refractory FL is a crucial development in addressing an ongoing unmet want within the FL remedy paradigm, offering sufferers a brand new choice that has proven remarkably excessive response charges and a longtime security profile.

Breyanzi has exhibited a constant security profile and throughout medical trials, any grade cytokine launch syndrome (CRS) occurred in 53% of sufferers, together with Grade >3 CRS in 4% of sufferers. The median time to onset was 5 days (vary: 1 to 63 days). Any grade neurologic occasions (NEs) occurred in 31% of sufferers, with Grade >3 NEs occurring in 10% of sufferers. The median time to onset of NEs was 8 days (vary: 1 to 63 days). The protection profile of Breyanzi permits for the choice of outpatient remedy and administration of sufferers. Sufferers within the TRANSCEND FL research have been handled within the inpatient and outpatient setting.

The lymphoma neighborhood has felt an pressing want for developments within the remedy of relapsed or refractory follicular lymphoma, stated Meghan Gutierrez, chief govt officer, Lymphoma Analysis Basis. The approval of Breyanzi presents sufferers a brand new and significant remedy choice that gives hope for lasting remission, and we’re grateful to those that have contributed to this thrilling milestone for sufferers.

Bristol Myers Squibb presents numerous packages and sources to deal with the wants of sufferers and caregivers, and offers assist that permits for entry to therapies, together with Breyanzi. Bristol Myers Squibb additionally helps the affected person and doctor remedy expertise by offering Cell Remedy 360, a digital service platform, which optimizes entry to related info, manufacturing updates, and affected person and caregiver assist.

NCCN makes no warranties of any form in anyway concerning their content material, use or utility and disclaims any accountability for his or her utility or use in any method.
Remedy course of consists of leukapheresis, manufacturing, administration, and adversarial occasion monitoring.

About TRANSCEND FL
TRANSCEND FL (NCT04245839) is an open-label, world, multicenter, Part 2, single-arm research to find out the efficacy and security of Breyanzi in sufferers with relapsed or refractory indolent B-cell non-Hodgkin lymphoma, together with follicular lymphoma. The first consequence measure is total response fee, together with finest total response of full response or partial response as decided by an Unbiased Overview Committee. Secondary consequence measures embrace full response fee, period of response, progression-free survival, and security.

About FL
Follicular lymphoma (FL) is the second most typical type of non-Hodgkin lymphoma (NHL) and the most typical subtype of indolent NHL, accounting for 20 to 30 p.c of all NHL instances. The typical age of prognosis for FL is 65 years of age. FL develops when white blood cells cluster collectively to kind lumps in an individual’s lymph nodes or organs. It’s characterised by durations of remission and relapse, and the illness turns into tougher to deal with after relapse or illness development.

About Breyanzi
Breyanzi is a CD19-directed CAR T cell remedy with a 4-1BB costimulatory area, which boosts the enlargement and persistence of the CAR T cells. Breyanzi is created from a affected person’s personal T cells, that are collected and genetically reengineered to develop into CAR T cells which are then delivered by way of infusion as a one-time remedy.

Breyanzi is accredited within the U.S. for the remedy of relapsed or refractory massive B-cell lymphoma (LBCL) after at the very least one prior line of remedy and obtained accelerated approval for the remedy of relapsed or refractory persistent lymphocytic leukemia or small lymphocytic lymphoma after at the very least two prior traces of remedy. Breyanzi can also be accredited in Japan, the European Union (EU), and Switzerland for the second-line remedy or relapsed or refractory LBCL, and in Japan, the European Union, Switzerland, the UK and Canada for relapsed and refractory LBCL after two or extra traces of systemic remedy.

Bristol Myers Squibb’s medical growth program for Breyanzi consists of medical research in different forms of lymphoma. For extra info, go to clinicaltrials.gov.

Indication
BREYANZI is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the remedy of:

• grownup sufferers with massive B-cell lymphoma (LBCL), together with diffuse massive B-cell lymphoma (DLBCL) not in any other case specified (together with DLBCL arising from indolent lymphoma), high-grade B cell lymphoma, main mediastinal massive B-cell lymphoma, and follicular lymphoma grade 3B, who’ve:
  • refractory illness to first-line chemoimmunotherapy or relapse inside 12 months of first-line chemoimmunotherapy; or
  • refractory illness to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and usually are not eligible for hematopoietic stem cell transplantation (HSCT) resulting from comorbidities or age; or
  • relapsed or refractory illness after two or extra traces of systemic remedy.

Limitations of Use: BREYANZI isn’t indicated for the remedy of sufferers with main central nervous system lymphoma.

• Grownup sufferers with relapsed or refractory persistent lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who’ve obtained at the very least 2 prior traces of remedy, together with a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor. This indication is accredited beneath accelerated approval primarily based on response fee and period of response. Continued approval for this indication could also be contingent upon verification and outline of medical profit in confirmatory trial(s).
• Grownup sufferers with relapsed or refractory follicular lymphoma (FL) who’ve obtained 2 or extra prior traces of systemic remedy. This indication is accredited beneath accelerated approval primarily based on response fee and period of response. Continued approval for this indication could also be contingent upon verification and outline of medical profit in confirmatory trial(s).

Necessary Security Data

BOXED WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, AND SECONDARY HEMATOLOGICAL MALIGNANCIES

• Cytokine Launch Syndrome (CRS), together with deadly or life-threatening reactions, occurred in sufferers receiving BREYANZI. Don’t administer BREYANZI to sufferers with energetic an infection or inflammatory issues. Deal with extreme or life-threatening CRS with tocilizumab with or with out corticosteroids.
• Neurologic toxicities, together with deadly or life-threatening reactions, occurred in sufferers receiving BREYANZI, together with concurrently with CRS, after CRS decision or within the absence of CRS. Monitor for neurologic occasions after remedy with BREYANZI. Present supportive care and/or corticosteroids as wanted.
• T cell malignancies have occurred following remedy of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, together with BREYANZI.
• BREYANZI is obtainable solely via a restricted program beneath a Threat Analysis and Mitigation Technique (REMS) referred to as the BREYANZI REMS.

Cytokine Launch Syndrome (CRS)
Cytokine launch syndrome (CRS), together with deadly or life-threatening reactions, occurred following remedy with BREYANZI. In medical trials of BREYANZI which enrolled a complete of 614 sufferers with non-Hodgkin lymphoma (NHL), CRS occurred in 53% of sufferers, together with Grade 3 or increased CRS in 4% of sufferers. The median time to onset was 5 days (vary: 1 to 63 days). CRS resolved in 98% of sufferers with median period of 5 days (vary: 1 to 37 days). The commonest manifestations of CRS (>10%) have been fever, hypotension, tachycardia, chills, hypoxia and headache.

Severe occasions that could be related to CRS embrace cardiac arrhythmias (together with atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, diffuse alveolar harm, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).

Be sure that 2 doses of tocilizumab can be found previous to infusion of BREYANZI.

Neurologic Toxicities
Neurologic toxicities that have been deadly or life-threatening, together with immune effector cell-associated neurotoxicity syndrome (ICANS), occurred following remedy with BREYANZI. Severe occasions together with cerebral edema and seizures occurred with BREYANZI. Deadly and severe instances of leukoencephalopathy, some attributable to fludarabine, additionally occurred.

In medical trials of BREYANZI, CAR T cell-associated neurologic toxicities occurred in 31% of sufferers, together with > Grade 3 instances in 10% of sufferers. The median time to onset of neurotoxicity was 8 days (vary: 1 to 63 days). Neurologic toxicities resolved in 87% of sufferers with a median period of 8 days (vary: 1 to 119 days). Of sufferers creating neurotoxicity, 81% additionally developed CRS.

The commonest neurologic toxicities ( ‰¥ 5%) included encephalopathy, tremor, aphasia, headache, dizziness, and delirium.

CRS and Neurologic Toxicities Monitoring
Monitor sufferers every day for at the very least 7 days following BREYANZI infusion at a REMS-certified healthcare facility for indicators and signs of CRS and neurologic toxicities and assess for different causes of neurological signs. Monitor sufferers for indicators and signs of CRS and neurologic toxicities for at the very least 4 weeks after infusion and deal with promptly. On the first signal of CRS, institute remedy with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated. Handle neurologic toxicity with supportive care and/or corticosteroid as wanted. Counsel sufferers to hunt quick medical consideration ought to indicators or signs of CRS or neurologic toxicity happen at any time.

BREYANZI REMS
Due to the danger of CRS and neurologic toxicities, BREYANZI is obtainable solely via a restricted program beneath a Threat Analysis and Mitigation Technique (REMS) referred to as the BREYANZI REMS. The required parts of the BREYANZI REMS are:

• Healthcare amenities that dispense and administer BREYANZI should be enrolled and adjust to the REMS necessities.
• Licensed healthcare amenities will need to have on-site, quick entry to tocilizumab.
• Be sure that a minimal of two doses of tocilizumab can be found for every affected person for infusion inside 2 hours after BREYANZI infusion, if wanted for remedy of CRS.

Additional info is obtainable at www.BreyanziREMS.com, or contact Bristol Myers Squibb at 1-866-340-7332.

Hypersensitivity Reactions
Allergic reactions could happen with the infusion of BREYANZI. Severe hypersensitivity reactions, together with anaphylaxis, could also be resulting from dimethyl sulfoxide (DMSO).

Severe Infections
Extreme infections, together with life-threatening or deadly infections, have occurred in sufferers after BREYANZI infusion. In medical trials of BREYANZI, infections of any grade occurred in 33% of sufferers, with Grade 3 or increased infections occurring in 12% of all sufferers. Grade 3 or increased infections with an unspecified pathogen occurred in 7%, bacterial infections in 4%, viral infections in 2%, and fungal infections in 0.7% of sufferers. One affected person who obtained 4 prior traces of remedy developed a deadly case of John Cunningham (JC) virus progressive multifocal leukoencephalopathy 4 months after remedy with BREYANZI.

Febrile neutropenia developed after BREYANZI infusion in 8% of sufferers. Febrile neutropenia 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.

Monitor sufferers for indicators and signs of an infection earlier than and after BREYANZI administration and deal with appropriately. Administer prophylactic antimicrobials in response to normal institutional pointers. Keep away from administration of BREYANZI in sufferers with clinically vital, energetic systemic infections.

Viral reactivation: Hepatitis B virus (HBV) reactivation, in some instances leading to fulminant hepatitis, hepatic failure, and dying, can happen in sufferers handled with medication directed towards B cells. In medical trials of BREYANZI, 26 of 29 sufferers with prior historical past of HBV have been handled with concurrent antiviral suppressive remedy. Carry out screening for HBV, HCV, and HIV in accordance with medical pointers earlier than assortment of cells for manufacturing. In sufferers with prior historical past of HBV, take into account concurrent antiviral suppressive remedy to stop HBV reactivation per normal pointers.

Extended Cytopenias
Sufferers could exhibit cytopenias not resolved for a number of weeks following lymphodepleting chemotherapy and BREYANZI infusion. In medical trials of BREYANZI, Grade 3 or increased cytopenias persevered at Day 29 following BREYANZI infusion in 34% of sufferers, and included thrombocytopenia in 24%, neutropenia in 22%, and anemia in 7% of sufferers. Monitor full blood counts previous to and after BREYANZI administration.

Hypogammaglobulinemia
B-cell aplasia and hypogammaglobulinemia can happen in sufferers receiving remedy with BREYANZI. In medical trials of BREYANZI, hypogammaglobulinemia was reported as an adversarial response in 10% of sufferers. Hypogammaglobulinemia, both as an adversarial response or laboratory IgG stage beneath 500 mg/dL after infusion, was reported in 29% of sufferers. Monitor immunoglobulin ranges after remedy with BREYANZI and handle utilizing an infection precautions, antibiotic prophylaxis, and immunoglobulin substitute as clinically indicated.

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

Secondary Malignancies
Sufferers handled with BREYANZI could develop secondary malignancies. T cell malignancies have occurred following remedy of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, together with BREYANZI. Mature T cell malignancies, together with CAR-positive tumors, could current as quickly as weeks following infusion, and should embrace deadly outcomes. Monitor lifelong for secondary malignancies. Within the occasion {that a} secondary malignancy happens, contact Bristol Myers Squibb at 1-888-805-4555 for reporting and to acquire directions on assortment of affected person samples for testing.

Results on Potential (OTC:) to Drive and Use Machines
As a result of potential for neurologic occasions, together with altered psychological standing or seizures, sufferers receiving BREYANZI are in danger for creating altered or decreased consciousness or impaired coordination within the 8 weeks following BREYANZI administration. Advise sufferers to chorus from driving and fascinating in hazardous occupations or actions, comparable to working heavy or doubtlessly harmful equipment, for at the very least 8 weeks.

Immune Effector Cell-Related Hemophagocytic Lymphohistiocytosis-Like Syndrome (IEC-HS)
Immune Effector Cell-Related Hemophagocytic Lymphohistiocytosis (IEC-HS), together with deadly or life-threatening reactions, occurred following remedy with BREYANZI. Three of 89 (3%) security evaluable sufferers with R/R CLL/SLL developed IEC-HS. Time to onset of IEC-HS ranged from 7 to 18 days. Two of the three sufferers developed IEC-HS within the setting of ongoing CRS and 1 within the setting of ongoing neurotoxicity. IEC-HS was deadly in 2 of three sufferers. One affected person had deadly IEC-HS and one had ongoing IEC-HS at time of dying. IEC-HS is a life-threatening situation with a excessive mortality fee if not acknowledged and handled early. Remedy of IEC-HS ought to be administered per present observe pointers.

Antagonistic Reactions
The commonest adversarial reactions (incidence ‰¥ 30%) in:

• LBCL are fever, cytokine launch syndrome, fatigue, musculoskeletal ache, and nausea. The commonest Grade 3-4 laboratory abnormalities embrace lymphocyte depend lower, neutrophil depend lower, platelet depend lower, and hemoglobin lower.
• CLL/SLL are cytokine launch syndrome, encephalopathy, fatigue, musculoskeletal ache, nausea, edema, and diarrhea. The commonest Grade 3-4 laboratory abnormalities embrace neutrophil depend lower, white blood cell lower, hemoglobin lower, platelet depend lower, and lymphocyte depend lower.
• FL are cytokine launch syndrome. The commonest Grade 3-4 laboratory abnormalities embrace lymphocyte depend decreased, neutrophil depend decreased, and white blood cell lower.

Please see full Prescribing Data, together with Boxed WARNINGS and Remedy 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 supply every affected person a greater, more healthy life and to make remedy 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 personalised medication, and thru revolutionary digital platforms, are turning information into insights that sharpen their focus. Deep understanding of causal human biology, cutting-edge capabilities and differentiated analysis platforms uniquely place the corporate to method 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 prognosis to survivorship. As a frontrunner in most cancers care, Bristol Myers Squibb is working to empower all individuals with most cancers to have a greater future.

Study 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 revolutionary medicines that assist sufferers prevail over severe ailments. For extra details about Bristol Myers Squibb, go to us at BMS.com or comply with us on LinkedIn, Twitter, YouTube, Fb (NASDAQ:) and Instagram.

Cautionary Assertion Concerning Ahead-Trying Statements
This press launch incorporates forward-looking statements throughout the which means of the Non-public 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 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, targets, plans and goals 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 are tough to foretell, could also be past our management and will trigger our future monetary outcomes, targets, plans and goals to vary materially from these expressed in, or implied by, the statements. These dangers, assumptions, uncertainties and different elements embrace, amongst others, whether or not Breyanzi (lisocabtagene maraleucel) for the extra indication described on this launch might be commercially profitable, any advertising and marketing approvals, if granted, could have vital limitations on their use, and that continued approval of Breyanzi for such further indication described on this launch could also be contingent upon verification and outline of medical profit in confirmatory trials. 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, notably these recognized within the cautionary assertion and threat elements dialogue in Bristol Myers Squibb’s Annual Report on Kind 10-Okay for the 12 months ended December 31, 2023, as up to date by our subsequent Quarterly Studies on Kind 10-Q, Present Studies on Kind 8-Okay and different filings with the Securities and Alternate 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 on account of new info, future occasions, modified circumstances or in any other case.

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