Capillary Leak Syndrome

Breyanzi offers a personalized treatment option delivered as a one-time infusion that provides deep and durable responses for patients with relapsed or refractory CLL or SLL who have historically had no standard of care In TRANSCEND CLL 004, the first pivotal multicenter trial to evaluate a CAR T cell therapy in patients with relapsed or refractory CLL or SLL, 20% of patients treated with Breyanzi achieved a complete response (CR) with median duration of CR not reached, along with an established safety pro > Breyanzi is now FDA approved for relapsed or refractory large B-cell lymphoma and CLL or SLL, bringing this differentiated CD19-directed CAR T cell therapy to more patients PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced the U.S. Food and Drug Administration (FDA) has granted accelerated approval of Breyanzi® (lisocabtagene maraleucel; liso-cel), a CD19-directed chimeric antigen receptor (CAR) T cell therapy, for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least two prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor. This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). In R/R CLL or SLL, Breyanzi is delivered through a treatment process which culminates in a one-time infusion* with a single dose containing 90 to 110 x 106 CAR-positive viable T cells. Please see the Important Safety Information section below, including Boxed WARNINGS for Breyanzi regarding Cytokine Release Syndrome (CRS), Neurologic Toxicities, and Secondary Hematological Malignancies. This press release features multimedia. View the full release here: Product image for download (Photo: Bristol Myers Squibb) “CAR T cell therapies represent a transformative treatment option for patients with certain types of blood cancers,” said Bryan Campbell, senior vice president, Head of Commercial, Cell Therapy, Bristol Myers Squibb. “For years, attempts to bring other CAR T cell therapies to patients with relapsed or refractory CLL or SLL met challenges and found little success. With the approval of Breyanzi as the first CAR T for relapsed or refractory CLL or SLL, we are now able to offer these patients a personalized option, while further expanding access across the broadest array of B-cell malignancies, to address this critical unmet need.” CLL and SLL are among the most common types of B-cell lymphoma. Treatments for people living with CLL or SLL primarily consist of targeted therapies including BTK- and BCL-2 inhibitors. However, patients often experience relapse or become refractory following early-line treatment with these therapies and there is no established standard of care for patients with double-class exposed CLL or SLL. After relapsing or becoming refractory to these therapies, patients have few options and poor outcomes, including lack of durable complete responses. The Phase 1/2 open-label, single-arm TRANSCEND CLL 004 study was the first pivotal multicenter trial to evaluate a CAR T cell therapy in patients with relapsed or refractory CLL or SLL. The CR rate associated with Breyanzi treatment was 20% (95% CI: 11.1-31.8). Among patients who achieved a CR, median duration of response was not reached (95% CI: 15 months-NR) at the time of data cutoff. Among all responders (ORR = 45%; 95% CI: 32.3-57.5), median duration of response was 35.3 months (95% CI: 12.4-NR). High rates of minimal residual disease (MRD) negative status were observed across patients treated with Breyanzi who achieved a CR, with an MRD-negativity rate of 100% in the blood (95% CI: 75.3-100) and 92.3% in the bone marrow (95% CI: 64-99.8). “CLL and SLL are currently considered incurable diseases with few treatment options in the relapsed setting that can confer complete responses, something that has historically been associated with improved long-term outcomes,” said Tanya Siddiqi, M.D., lead investigator and Associate Professor, Division of Lymphoma, City of Hope National Medical Center. “The FDA approval of liso-cel in relapsed or refractory CLL and SLL after treatment with prior BTKi and BCL2i is a remarkable breakthrough, shifting the treatment paradigm from continuous therapy with sequential regimens to overcome drug resistance, to a one-time personalized T-cell based approach that has the potential to offer patients complete and lasting remission.” Among 89 patients in the study treated with Breyanzi, occurrences of cytokine release syndrome (CRS) and neurologic events (NEs) were mostly low grade. Any grade CRS occurred in 83% of patients, with Grade 3 CRS occurring in 9% of patients. No Grade 4/5 CRS events were reported. Any grade NEs were reported in 46% of patients, with Grade 3 NEs reported in 20% of patients and one case of Grade 4 NE reported. No Grade 5 NEs were reported. “For people struggling with relapsed or refractory CLL or SLL, current treatment choices are limited,” said Dr. Brian Koffman, physician, CLL patient and cofounder, executive vice president and chief medical officer of CLL Society. “The approval of Breyanzi as the first CAR T cell therapy available for relapsed or refractory CLL or SLL brings new hope to these patients with the potential for durable responses after a single CAR T infusion. We are grateful to the patients and their families who enter the trials and to all the researchers involved in making possible this important new treatment option in CLL and SLL.” Bristol Myers Squibb offers various programs and resources to address the needs of patients and caregivers, and provides support that allows for access to therapies, including Breyanzi. Bristol Myers Squibb also supports the patient and physician treatment experience by providing Cell Therapy 360, a digital service platform, which optimizes access to relevant information, manufacturing updates, and patient and caregiver support. About TRANSCEND CLL 004 TRANSCEND CLL 004 (NCT03331198) is a Phase 1/2 open-label, single-arm, multicenter study evaluating Breyanzi in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma. The Phase 1 dose escalation portion of the study assessed the safety and recommended dose for the subsequent Phase 2 expansion cohort. The Phase 2 portion of the study is evaluating Breyanzi at the recommended dose from the Phase 1 monotherapy arm. The primary endpoint of the Phase 2 portion of the study is complete response rate, including complete remission with incomplete bone marrow recovery, based on independent review committee according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines. About CLL and SLL Chronic lymphocytic leukemia (CLL) is one of the most common types of leukemia in adults. In CLL, too many blood stem cells in the bone marrow become abnormal lymphocytes, and these abnormal cells have difficulty fighting infections. As the number of abnormal cells grows, there is less room for healthy white blood cells, red blood cells and platelets. Small lymphocytic lymphoma (SLL) also affects the lymphocytes, with cancer cells found mostly in the lymph nodes. While there are several treatments available for CLL and SLL, there is a need for additional effective therapies as there is no standard of care for relapsed or refractory CLL or SLL after prior therapy with targeted agents, such as Bruton tyrosine kinase (BTK) and B-cell lymphoma 2 (BCL-2) inhibitors. Patients with relapsed or refractory disease have limited treatment options and generally experience shorter periods of response with each subsequent treatment. About Breyanzi Breyanzi is a CD19-directed CAR T cell therapy with a 4-1BB costimulatory domain, which enhances the expansion and persistence of the CAR T cells. Breyanzi is made from a patient’s own T cells, which are collected and genetically reengineered to become CAR T cells that are then delivered via infusion as a one-time treatment. Breyanzi is approved in the U.S., Japan and Europe for the second-line treatment of relapsed or refractory LBCL, and in Japan, Europe, Switzerland, and Canada for relapsed and refractory LBCL after two or more lines of systemic therapy. Bristol Myers Squibb’s clinical development program for Breyanzi includes clinical studies in other types of lymphoma. For more information, visit clinicaltrials.gov. * Treatment process includes leukapheresis, manufacturing, administration, and adverse event monitoring. Indication BREYANZI is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of: adult patients with large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B, who have: refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy; or refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplantation (HSCT) due to comorbidities or age; or relapsed or refractory disease after two or more lines of systemic therapy. Limitations of Use: BREYANZI is not indicated for the treatment of patients with primary central nervous system lymphoma. adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least 2 prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a B-cell lymphoma 2 (BCL-2) inhibitor. This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). Important Safety Information WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, AND SECONDARY HEMATOLOGICAL MALIGNANCIES Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving BREYANZI. Do not administer BREYANZI to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab with or without corticosteroids. Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving BREYANZI, including concurrently with CRS, after CRS resolution or in the absence of CRS. Monitor for neurologic events after treatment with BREYANZI. Provide supportive care and/or corticosteroids as needed. T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including BREYANZI. BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS. Cytokine Release Syndrome Cytokine release syndrome (CRS), including fatal or life-threatening reactions, occurred following treatment with BREYANZI. Among patients receiving BREYANZI for LBCL (N=418), CRS occurred in 46% (190/418), including ≥ Grade 3 CRS in 3.1% of patients. In patients receiving BREYANZI after two or more lines of therapy for LBCL, CRS occurred in 46% (122/268), including ≥ Grade 3 CRS in 4.1% of patients. One patient had fatal CRS and 2 had ongoing CRS at time of death. The median time to onset was 5 days (range: 1 to 15 days). CRS resolved in 98% with a median duration of 5 days (range: 1 to 17 days). In patients receiving BREYANZI after one line of therapy for LBCL, CRS occurred in 45% (68/150), including Grade 3 CRS in 1.3% of patients. The median time to onset was 4 days (range: 1 to 63 days). CRS resolved in all patients with a median duration of 4 days (range: 1 to 16 days). Among patients receiving BREYANZI for CLL/SLL, CRS occurred in 83% (74/89), including Grade 3 CRS in 9% of patients. The median time to onset was 4 days (range: 1 to 18 days). CRS resolved in 97% with a median duration of 6 days (range: 2 to 37 days). The most common manifestations of CRS (≥ 10% in LBCL or CLL/SLL) included fever (94% LBCL; 97% CLL/SLL), hypotension (42% LBCL; 46% CLL/SLL), tachycardia (28% LBCL), chills (23% LBCL; 43% CLL/SLL), hypoxia (16% LBCL; 35% CLL/SLL), sinus tachycardia (22% CLL/SLL), and headache (12% LBCL; 18% CLL/SLL). Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, diffuse alveolar damage, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS). Ensure that 2 doses of tocilizumab are available prior to infusion of BREYANZI. Of the patients who received BREYANZI for LBCL (n=418) and CLL/SLL (n=89), 23% (LBCL) and 64% (CLL/SLL) received tocilizumab and/or a corticosteroid for CRS, including 10% (LBCL) and 33% (CLL/SLL) who received tocilizumab only and 2.2% (LBCL) and 2.2% (CLL/SLL) who received corticosteroids only. Neurologic Toxicities Neurologic toxicities that were fatal or life-threatening, including immune effector cell-associated neurotoxicity syndrome (ICANS), occurred following treatment with BREYANZI. Serious events including cerebral edema and seizures occurred with BREYANZI. Fatal and serious cases of leukoencephalopathy, some attributable to fludarabine, also occurred. In patients receiving BREYANZI after two or more lines of therapy for LBCL, CAR T cell-associated neurologic toxicities occurred in 35% (95/268), including ≥ Grade 3 cases in 12% of patients. Three patients had fatal neurologic toxicity and 7 had ongoing neurologic toxicity at time of death. The median time to onset of neurotoxicity was 8 days (range: 1 to 46 days). Neurologic toxicities resolved in 85% of patients with a median duration of 12 days (range: 1 to 87 days). In patients receiving BREYANZI after one line of therapy for LBCL, CAR T cell-associated neurologic toxicities occurred in 27% (41/150) of patients, including Grade 3 cases in 7% of patients. The median time to onset of neurologic toxicity was 8 days (range: 1 to 63 days). The median duration of neurologic toxicity was 6 days (range: 1 to 119 days). In all patients combined receiving BREYANZI for LBCL, CAR T cell-associated neurologic toxicities occurred in 33% (136/418), including ≥ Grade 3 cases in 10% of patients. The median time to onset was 8 days (range: 1 to 63), with 87% of cases developing by 16 days. Neurologic toxicities resolved in 85% of patients with a median duration of 11 days (range: 1 to 119 days). Of patients developing neurotoxicity, 77% (105/136) also developed CRS. In patients receiving BREYANZI for CLL/SLL, CAR T cell-associated neurologic toxicities occurred in 46% (41/89), including Grade 3 cases in 20% of patients and a single Grade 4 case. The median time to onset of neurotoxicity was 7 days (range: 1 to 21 days), with 95% of cases developing by 16 days. Neurologic toxicities resolved in 85% with a median duration of 7 days (range: 1 to 83 days). Of patients developing neurotoxicity, 95% (39/41) also developed CRS. The most common neurologic toxicities (≥ 5% in LBCL or CLL) included encephalopathy (20% LBCL; 36% CLL/SLL), tremor (13% LBCL; 14% CLL/SLL), aphasia (8% LBCL; 8% CLL/SLL), headache (6% LBCL; 9% CLL/SLL), dizziness (6% LBCL), and delirium (5% LBCL; 12% CLL/SLL). CRS and Neurologic Toxicities Monitoring Monitor patients daily for at least 7 days following BREYANZI infusion at a REMS-certified healthcare facility for signs and symptoms of CRS and neurologic toxicities and assess for other causes of neurological symptoms. Monitor patients for signs and symptoms of CRS and neurologic toxicities for at least 4 weeks after infusion and treat promptly. At the first sign of CRS, institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids as indicated. Manage neurologic toxicity with supportive care and/or corticosteroid as needed. Counsel patients to seek immediate medical attention should signs or symptoms of CRS or neurologic toxicity occur at any time. BREYANZI REMS Because of the risk of CRS and neurologic toxicities, BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS. The required components of the BREYANZI REMS are: Healthcare facilities that dispense and administer BREYANZI must be enrolled and comply with the REMS requirements. Certified healthcare facilities must have on-site, immediate access to tocilizumab. Ensure that a minimum of 2 doses of tocilizumab are available for each patient for infusion within 2 hours after BREYANZI infusion, if needed for treatment of CRS. Further information is available at , or contact Bristol-Myers Squibb at 1-866-340-7332. Hypersensitivity Reactions Allergic reactions may occur with the infusion of BREYANZI. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO). Serious Infections Severe infections, including life-threatening or fatal infections, have occurred in patients after BREYANZI infusion. In patients receiving BREYANZI, infections of any grade occurred in 36% (LBCL) and 35% (CLL/SLL), with Grade 3 or higher infections occurring in 12% (LBCL) and 16% (CLL/SLL) of all patients. Grade 3 or higher infections with an unspecified pathogen occurred in 7% (LBCL) and 10% (CLL/SLL), bacterial infections in 4.3% (LBCL) and 2.2% (CLL/SLL), viral infections in 1.9% (LBCL) and 1.1% (CLL/SLL), and fungal infections in 0.5% (LBCL) and 2.2% (CLL/SLL). Febrile neutropenia developed after BREYANZI infusion in 8% (LBCL) and 12% (CLL/SLL) of patients. Febrile neutropenia may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids, and other supportive care as medically indicated. Monitor patients for signs and symptoms of infection before and after BREYANZI administration and treat appropriately. Administer prophylactic antimicrobials according to standard institutional guidelines. Avoid administration of BREYANZI in patients with clinically significant, active systemic infections. Viral reactivation: Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against B cells. In patients who received BREYANZI, 15 of 16 LBCL patients, and all 9 CLL/SLL patients with a prior history of HBV were treated with concurrent antiviral suppressive therapy. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing. In patients with prior history of HBV, consider concurrent antiviral suppressive therapy to prevent HBV reactivation per standard guidelines. Prolonged Cytopenias Patients may exhibit cytopenias not resolved for several weeks following lymphodepleting chemotherapy and BREYANZI infusion. Grade 3 or higher cytopenias persisted at Day 29 following BREYANZI infusion in 36% (LBCL) and 45% (CLL/SLL) of patients, and included thrombocytopenia in 28% (LBCL) and 23% (CLL/SLL), neutropenia in 21% (LBCL) and 35% (CLL/SLL), and anemia in 6% (LBCL) and 12% (CLL/SLL). Monitor complete blood counts prior to and after BREYANZI administration. Hypogammaglobulinemia B-cell aplasia and hypogammaglobulinemia can occur in patients receiving BREYANZI. In patients receiving BREYANZI, hypogammaglobulinemia was reported as an adverse reaction in 11% (LBCL) and 14% (CLL/SLL) of patients. Hypogammaglobulinemia, either as an adverse reaction or laboratory IgG level below 500 mg/dL after infusion, was reported in 28% (LBCL) and 37% (CLL/SLL) of patients. Monitor immunoglobulin levels after treatment with BREYANZI and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement as clinically indicated. Live vaccines: The safety of immunization with live viral vaccines during or following BREYANZI treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during BREYANZI treatment, and until immune recovery following treatment with BREYANZI. Secondary Malignancies Patients treated with BREYANZI may develop secondary malignancies. T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including BREYANZI. Mature T cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusion, and may include fatal outcomes. Monitor lifelong for secondary malignancies. In the event that a secondary malignancy occurs, contact Bristol-Myers Squibb at 1- 888-805-4555 for reporting and to obtain instructions on collection of patient samples for testing. Effects on Ability to Drive and Use Machines Due to the potential for neurologic events, including altered mental status or seizures, patients receiving BREYANZI are at risk for developing altered or decreased consciousness or impaired coordination in the 8 weeks following BREYANZI administration. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, for at least 8 weeks. Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome (IEC-HS) Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome (IEC-HS), including fatal or life-threatening reactions, occurred following treatment with BREYANZI. Three of 89 (3%) safety evaluable patients with R/R CLL/SLL developed IEC-HS. Time to onset of IEC-HS ranged from 7 to 18 days. Two of the 3 patients developed IEC-HS in the setting of ongoing CRS and 1 in the setting of ongoing neurotoxicity. IEC-HS was fatal in 2 of 3 patients. One patient had fatal IEC-HS and one had ongoing IEC-HS at time of death. IEC-HS is a life-threatening condition with a high mortality rate if not recognized and treated early. Treatment of IEC-HS should be administered per current practice guidelines. Adverse Reactions The most common nonlaboratory adverse reactions (incidence ≥ 30%) in: LBCL are fever, cytokine release syndrome, fatigue, musculoskeletal pain, and nausea. The most common Grade 3-4 laboratory abnormalities (≥ 30%) include lymphocyte count decrease, neutrophil count decrease, platelet count decrease, and hemoglobin decrease. CLL/SLL are cytokine release syndrome, encephalopathy, fatigue, musculoskeletal pain, nausea, and diarrhea. The most common Grade 3-4 laboratory abnormalities (≥ 30%) in CLL/SLL include neutrophil count decrease, white blood cell decrease, hemoglobin decrease, platelet count decrease, and lymphocyte count decrease. Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide. Bristol Myers Squibb: Creating a Better Future for People with Cancer Bristol Myers Squibb is inspired by a single vision — transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine and, through innovative digital platforms, are turning data into insights that sharpen their focus. Deep understanding of causal human biology, cutting-edge capabilities and differentiated research platforms uniquely position the company to approach cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. As a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future. About Bristol Myers Squibb Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram. Cautionary Statement Regarding Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995 regarding, among other things, the research, development and commercialization of pharmaceutical products. All statements that are not statements of historical facts are, or may be deemed to be, forward-looking statements. Such forward-looking statements are based on current expectations and projections about our future financial results, goals, plans and objectives and involve inherent risks, assumptions and uncertainties, including internal or external factors that could delay, divert or change any of them in the next several years, that are difficult to predict, may be beyond our control and could cause our future financial results, goals, plans and objectives to differ materially from those expressed in, or implied by, the statements. These risks, assumptions, uncertainties and other factors include, among others, whether Breyanzi (lisocabtagene maraleucel) for such additional indication described in this release will be commercially successful, that any marketing approvals, if granted, may have significant limitations on their use, and that continued approval of such product candidate for such additional indication described in this release may be contingent upon verification and description of clinical benefit in confirmatory trial(s). No forward-looking statement can be guaranteed. Forward-looking statements in this press release should be evaluated together with the many risks and uncertainties that affect Bristol Myers Squibb’s business and market, particularly those identified in the cautionary statement and risk factors discussion in Bristol Myers Squibb’s Annual Report on Form 10-K for the year ended December 31, 2023, as updated by our subsequent Quarterly Reports on Form 10-Q, Current Reports on Form 8-K and other filings with the Securities and Exchange Commission. The forward-looking statements included in this document are made only as of the date of this document and except as otherwise required by applicable law, Bristol Myers Squibb undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events, changed circumstances or otherwise. corporatefinancial-news

– Innovative design enables five-minute pegfilgrastim-cbqv delivery time – – Unique, automatic, retractable needle mechanism engineered to maximize safety and comfort for cancer patients receiving UDENYCA® – REDWOOD CITY, Calif., Feb. 21, 2024 (GLOBE NEWSWIRE) -- Coherus BioSciences, Inc. (Coherus, NASDAQ: CHRS) today announced the launch of UDENYCA ONBODY™, the company's on-body injector (OBI) presentation of UDENYCA® (pegfilgrastim-cbqv), is successfully underway, with a broad distribution of accounts nationwide ordering this innovative device, and patients now accessing its benefits. UDENYCA is a pegfilgrastim biosimilar administered the day after chemotherapy to decrease the incidence of infection as manifested by febrile neutropenia. “It’s exciting to have a new biosimilar pegfilgrastim on-body option, especially for those who live far away from their care centers,” said Kathleen Clifford, Clinical Oncology Nurse Practitioner at St. Luke's Health System. “The thoughtful design of this device, with its distinct features, has advantages for our patients and gives me confidence that their treatment will be administered even though it’s taking place away from the office.” UDENYCA ONBODY was designed with patients in mind; key features include a five-minute injection time, an indicator, status light and auditory signal that help patients confirm the dose has been administered and a strong and well-tolerated adhesive. After the dose is administered, the needle automatically retracts, which reduces the risk of needlestick injury. “We are excited that UDENYCA ONBODY is now available for cancer patients, and provider response to UDENYCA ONBODY’s unique features, including a five-minute injection time and novel retractable needle mechanism, has been very positive,” said Paul Reider, Coherus’ Chief Commercial Officer. “The ONBODY device is the third presentation in the UDENYCA franchise, which also includes a prefilled syringe and autoinjector. The growing demand for UDENYCA is evidence that innovating cancer care for patients is a winning strategy.” “The UDENYCA portfolio gives patients the opportunity to align their needs with a pegfilgrastim treatment plan,” said Maria Theodoulou, M.D., of New York Oncology Hematology. “Patients can continue to receive immune supportive care in a variety of settings, such as the clinic by a health care provider or at home via preset administration with UDENYCA ONBODY or self-administration with UDENYCA autoinjector. Where a cancer diagnosis takes empowerment away from patients, UDENYCA gives it back.” UDENYCA ONBODY is available through existing full-line and specialty distributors. Billing under the medical benefit for UDENYCA ONBODY is streamlined because it has the same permanent, product-specific Q-Code as the prefilled syringe, Q5111, and a unique NDC number of 70114-0130-01. UDENYCA Solutions™ offers healthcare professionals comprehensive practice and patient support that includes extensive patient assistance and office support to ensure successful access, billing, and reimbursement. More details regarding UDENYCA ONBODY, including video instructions for ONBODY preparation and application, can be found at . About UDENYCA UDENYCA® is the only pegfilgrastim brand approved in the United States available in three administration options—prefilled syringe (PFS), autoinjector (AI) and on-body injector—providing patients and healthcare providers with choice, control, and convenience. Since its launch in 2019, over 300,000 patients have been treated with UDENYCA. INDICATION UDENYCA® is a leukocyte growth factor indicated to: Decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. Increase survival in patients acutely exposed to myelosuppressive doses of radiation (Hematopoietic Subsyndrome of Acute Radiation Syndrome). Limitations of Use: UDENYCA® is not indicated for the mobilization of peripheral blood progenitor cells for hematopoietic stem cell transplantation. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS: Patients with a history of serious allergic reactions to pegfilgrastim products or filgrastim products. Reactions have included anaphylaxis. WARNINGS AND PRECAUTIONS: Fatal splenic rupture: Evaluate patients who report left upper abdominal or shoulder pain for an enlarged spleen or splenic rupture. Acute respiratory distress syndrome (ARDS): Evaluate patients who develop fever, lung infiltrates, or respiratory distress. Discontinue UDENYCA® in patients with ARDS. Serious allergic reactions, including anaphylaxis: The majority of reported events occurred upon initial exposure. Allergic reactions, including anaphylaxis, can recur within days after the discontinuation of initial anti-allergic treatment. Permanently discontinue UDENYCA® in patients with serious allergic reactions. Allergies to Acrylics: The on-body injector (OBI) for UDENYCA uses acrylic adhesive. For patients who have reactions to acrylic adhesives, use of this product may result in a significant reaction. Sickle cell crises: Severe and sometimes fatal crises have occurred. Discontinue UDENYCA® if sickle cell crisis occurs. Glomerulonephritis: The diagnoses were based upon azotemia, hematuria (microscopic and macroscopic), proteinuria, and renal biopsy. Generally, events resolved after dose reduction or discontinuation. Evaluate and consider dose-reduction or interruption of UDENYCA® if causality is likely. Leukocytosis: White blood cell (WBC) counts of 100 x 109/L or greater have been observed in patients receiving pegfilgrastim products. Monitoring of complete blood count (CBC) during UDENYCA® therapy is recommended. Thrombocytopenia: Thrombocytopenia has been reported in patients receiving pegfilgrastim. Monitor platelet counts. Capillary Leak Syndrome: Has been reported after G-CSF administration, including pegfilgrastim products, and is characterized by hypotension, hypoalbuminemia, edema, and hemoconcentration. Episodes vary in frequency, severity and may be life-threatening if treatment is delayed. If symptoms develop, closely monitor and give standard symptomatic treatment, which may include a need for intensive care. Potential for Tumor Growth Stimulatory Effects on Malignant Cells: The possibility that pegfilgrastim products act as a growth factor for any tumor type, including myeloid malignancies and myelodysplasia, diseases for which pegfilgrastim products are not approved, cannot be excluded. Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML) in Patients with Breast and Lung Cancer: MDS and AML have been associated with the use of pegfilgrastim in conjunction with chemotherapy and/or radiotherapy in patients with breast and lung cancer. Monitor patients for sign and symptoms of MDS/AML in these settings. Potential Device failures: Missed or partial doses have been reported for products administered via on-body injectors due to the device not performing as intended. In the event of a missed or partial dose, patients may be at increased risk of events such as neutropenia, febrile neutropenia and/or infection than if the dose had been correctly delivered. Instruct patients using the OBI to notify their healthcare professional immediately to determine the need for a replacement dose of UDENYCA if they suspect that the device may not have performed as intended. Aortitis: Has been reported in patients receiving pegfilgrastim products, occurring as early as the first week after start of therapy. Manifestations may include generalized signs and symptoms such as fever, abdominal pain, malaise, back pain, and increased inflammatory markers (e.g., c-reactive protein and white blood cell count). Consider aortitis when signs and symptoms develop without known etiology. Discontinue UDENYCA® if aortitis is suspected. Nuclear Imaging: Increased hematopoietic activity of the bone marrow in response to growth factor therapy has been associated with transient positive bone imaging changes. Consider when interpreting bone imaging results. ADVERSE REACTIONS: Most common adverse reactions (≥ 5% difference in incidence compared to placebo) are bone pain and pain in extremity. To report SUSPECTED ADVERSE REACTIONS, contact Coherus BioSciences at 1-800-4-UDENYCA (1-800-483-3692) or FDA at 1-800-FDA-1088 or . Full Prescribing Information, including instructions for use, are available at About Coherus BioSciences Coherus is a commercial-stage biopharmaceutical company focused on the research, development and commercialization of innovative immunotherapies to treat cancer. Coherus is developing an innovative immuno-oncology pipeline that will be synergistic with its proven commercial capabilities in oncology. Coherus’ immuno-oncology pipeline includes multiple antibody immunotherapy candidates focused on enhancing the innate and adaptive immune responses to enable a robust immunologic response and enhance outcomes for patients with cancer. Casdozokitug is a novel anti-IL-27 antibody currently being evaluated in two ongoing clinical studies: a Phase 1/2 study in advanced solid tumors and a Phase 2 study in hepatocellular carcinoma. CHS-114 is a highly selective, competitively positioned, ADCC-enhanced anti-CCR8 antibody currently in a Phase 1/2 study as a monotherapy in patients with advanced solid tumors. CHS-1000 is a preclinical candidate targeting immune-suppressive mechanisms via the novel pathway ILT4 with an IND filing planned in the first half of 2024. Coherus markets LOQTORZI™ (toripalimab-tpzi), a novel next generation PD-1 inhibitor, UDENYCA® (pegfilgrastim-cbqv), a biosimilar of Neulasta®, CIMERLI® (ranibizumab-eqrn), a biosimilar of Lucentis®, and YUSIMRY™ (adalimumab-aqvh), a biosimilar of Humira®. Forward-Looking Statements Except for the historical information contained herein, the matters set forth in this press release are forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995 including, but not limited to, statements regarding the timing for an IND filing for CHS-1000; whether Coherus’ immuno-oncology pipeline will have synergies with its capabilities in oncology; and whether there will be demand growth for UDENYCA. Such forward-looking statements involve substantial risks and uncertainties that could cause Coherus’ actual results, performance or achievements to differ significantly from any future results, performance or achievements expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, risks and uncertainties inherent in the clinical drug development process; risks related to our existing and potential collaboration partners; risks of the drug development position of Coherus’ competitors; the risks and uncertainties of the regulatory approval process, including the speed of regulatory review; the timing of Coherus’ regulatory filings; the risk of FDA review issues; the risk that Coherus is unable to complete commercial transactions and other matters that could affect the availability or commercial potential of Coherus’ drug candidates; and the risks and uncertainties of possible litigation. All forward-looking statements contained in this press release speak only as of the date of this press release. Coherus undertakes no obligation to update or revise any forward-looking statements. For a further description of the significant risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to Coherus’ business in general, see Coherus’ Quarterly Report on Form 10-Q for the quarter ended September 30, 2023, filed with the Securities and Exchange Commission on November 6, 2023, including the section therein captioned “Risk Factors” and in other documents that Coherus files with the Securities and Exchange Commission. Coherus Contact Information Investors: Jami Taylor, Head of Investor Relations IR@coherus.com Media: Jodi Sievers, VP Corporate Communications media@coherus.com A photo accompanying this announcement is available at UDENYCA ONBODY™ UDENYCA ONBODY™ a Novel and Proprietary State-of-the-Art Delivery System for pegfilgrastim-cbqvFull Prescribing Information, including instructions for use, is available at

Engineering a patient’s immune cells into cancer treatments works for treating blood cancers, but has fallen short in solid tumors—until now. An Iovance Biotherapeutics treatment employing a different type of cell has won accelerated FDA approval for advanced melanoma, marking the first product approval of any cell therapy for a solid tumor. The regulatory decision announced Friday covers melanoma in adults whose cancer cannot be surgically removed or has spread following treatment with an immunotherapy or a targeted cancer therapy. The cell therapy of San Carlos, California-based Iovance, known in development as lifileucel, will be marketed under the brand name Amtagvi. Amtagvi, a one-time treatment, is made from a type of cell called a tumor-infiltrating lymphocyte, or TIL. The body produces TILs to fight cancer, and they are found in the tumor. The Iovance cell therapy is made by surgically removing a small piece of a patient’s tumor and isolating TILs from that sample. Those TILs are multiplied in a lab, then shipped back to the hospital for infusion into the patient. The TIL manufacturing process is similar to that of CAR T-therapies, which are made by harvesting and multiplying a patient’s T cells. One key difference is what happens in the lab. CAR T-treatments are engineered to go after a target on the surface of a cancer cell. TILs don’t need this engineering step because they already have the ability to recognize a patient’s cancer cells. Amtagvi’s Clinical Trial Results The FDA based its approval on the results of an open-label, single-arm Phase 2 clinical trial. Participants had advanced melanoma that was previously treated with at least one systemic therapy, including a type of immunotherapy called a checkpoint inhibitor, and if positive for a BRAF mutation, a BRAF inhibitor. The main goal was to measure the objective response rate and the duration of response. Of the 73 patients who received Amtagvi within the recommended dosing range, the overall response rate was 31.5%. The median duration of response was not reached. Results were published in in 2022 in the Journal for ImmunoTherapy of Cancer. The most common adverse reactions reported from the clinical trial included chills, fever, fatigue, faster than normal heart rate, and diarrhea. Amtagvi’s label carries a black box warning that the treatment can lead to death. In the clinical trial, treatment-related mortality was 7.6%. Adverse reactions associated with these deaths included severe infections, internal bleeding, kidney failure, respiratory failure, and abnormal heart rhythm. Patients may experience prolonged and severe cytopenia, which is a low levels of certain blood cells. The risk of heart and kidney injury are also flagged in the boxed warning. CAR T-therapies also carry black box warnings, with the main complications risks being an excessive immune response called cytokine release syndrome and neurotoxicity. Fred Vogt, interim Iovance CEO and the company’s president and general counsel, noted that Amtagvi was not associated with either of these complications risks. FDA approval of CAR T-therapies came with Risk Evaluation Mitigation Strategies (REMS), programs to manage the risks associated with treatment. “The [Amtagvi] black box is pretty good, we think it’s much better than what the CAR T’s have,” Vogt said during a Friday conference call. “It doesn’t have a REMs, first and foremost, like the CAR T’s do. It’s got boxed warnings essentially for known risks, from the lymphodepletion and the IL-2 therapies that we provide.” Lymphodepletion, a key step in all cell therapies, involves using chemotherapy to reduce levels of a patient’s immune cells to improve the survival chances of the cell therapy. IL-2 refers an engineered version of a protein that stimulates an immune response. In the clinical trial, treatment with Amtagvi was followed by aldesleukin, an IL-2 therapy whose uses include the treatment of metastatic melanoma. In the Amtagvi treatment regimen, aldesleukin’s role is to activate the TILs’ anti-tumor activity. Aldesleukin also has risks: Its label includes a black box warning of a potential complication called capillary leak syndrome, leading to low blood pressure and low levels of the protein albumin in the blood. This complication can lead to life-threatening organ damage. Because aldesleukin is a key part of the Amtagvi treatment regimen, Iovance last year acquired global rights to Proleukin, an IL-2 product from Clinigen. Iovance paid £166.9 million (about $207.2 million) up front for the product’s rights. The acquisition agreement puts Clinigen in line for milestone payments and royalties from sales. Premium Pricing for the First TIL Cell Therapy Iovance set a $515,000 wholesale price for Amtagvi, which is higher than the $373,000 to $475,000 price range for currently available CAR T-therapies. The company will make the TIL therapy at its Philadelphia manufacturing facility. Together with a nearby contract manufacturer, the company says it has the capacity to produce Amtagvi for “several thousand patients annually.” The current manufacturing process is 34 days, which is a comparable to the lengthy, multi-step manufacturing process for CAR T-therapies. Vogt said Iovance believes it can improve Amtagvi’s manufacturing timeframe. Jim Ziegler, executive vice president, commercial, said about 30 authorized treatment centers are now ready to collect and ship tumor tissue for Amtagvi manufacturing. He expects that number to grow to 50 centers within the next three months. Based on interactions with payers, Ziegler said Iovance expects coverage of Amtagvi will be similar to insurance coverage of approved CAR T-therapies. TIL therapy competition is coming. The Achilles Therapeutics pipeline includes a TIL therapeutic candidate currently in a Phase 1/2 clinical trial evaluating it in combination with a checkpoint inhibitor as a potential treatment for melanoma. Lyell Immunopharma has a TIL therapy in early clinical development in melanoma, colorectal cancer, non-small cell lung cancer (NSCLC), and other solid tumors. Instil Bio’s pipeline includes a TIL in Phase 1 development in NSCLC, ovarian, and kidney cancers. Instil’s former lead program had reached mid-stage clinical development in advanced melanoma, but that therapy was discontinued in late 2022 due to a pipeline reprioritization. Iovance is also testing Amtagvi in combination with the Merck checkpoint inhibitor Keytruda as a frontline treatment for melanoma. This Phase 3 study will serve as the confirmatory clinical trial required of the therapy’s accelerated approval. The Iovance pipeline also includes tests of Amtagvi—by itself and in combination with checkpoint inhibitors—in cervical cancer, NSCLC, and head and neck squamous cell carcinoma. Another Iovance TIL therapy, LN-145, has reached pivotal testing in NSCLC. This study was placed under an FDA clinical hold in late December due to a fatality potentially related to the therapy’s preconditioning regimen. Vogt said Iovance is working to resolve the clinical hold and hopes to have an update in a few weeks. Photo by Iovance Biotherapeutics