T-Cell Leukemia

Abecma is a B-cell maturation antigen (BCMA) directed chimeric antigen receptor (CAR) T-cell therapy. Image Credit: Amy Lutz / Shutterstock. Despite the recent controversies surrounding chimeric antigen receptor (CAR)-T therapies, a US Food and Drug Administration (FDA) committee voted eight to three in favour of approval of Bristol Myers Squibb (BMS) and 2seventy bio’s Abecma (idecabtagene vicleucel) in patients with relapsed or refractory multiple myeloma (r/r MM). The FDA has not yet assigned a new target action date for the review of the supplemental biologics licence application (sBLA) for Abecma for this patient population of triple-class exposed r/r MM. The FDA had previously assigned a Prescription Drug User Fee Act (PDUFA) target action date of 16 December 2023, but the agency conveyed that it would miss the target date in November 2023. Around the same period, the agency had started an investigation to review the safety of chimeric antigen receptor (CAR)-T cell immunotherapies following reports of T cell malignancies in patients who received these immunotherapies. Abecma was one of the six therapies included in the inquiry. Furthermore, the agency was apprehensive of the ‘higher rate of early deaths’ for up to 15 months in the Abecma arm in the Phase III KarMMa-3 trial (NCT03651128), compared to the standard of care arm, as per the briefing documents. Another limitation noted in the documents was that a portion of the patients in the standard-of-care arm crossed over to receive Abecma. Because of this, ahead of the meeting, a key topic of discussion was whether the analysis provided ‘convincing evidence’ that Abecma provided an overall survival benefit, with the regulatory agency saying this evidence was not present, in the briefing document. The FDA advisory committee (AdCom) ultimately decided that the benefits outweigh the risks for Abecma as an earlier-line therapy in patients with multiple myeloma. See Also: China NMPA approves KeChow’s tunlametinib for melanoma FDA approves Orchard’s Lenmeldy gene therapy for MLD An AdCom is convened upon an FDA request to review and evaluate the safety and efficacy data of a particular therapy. However, the AdCom recommendations are non-binding, with the final decision made by the FDA. The agency rarely contradicts AdCom’s recommendations, although there have been a few cases where this has happened. In 2021, the agency granted accelerated approval to Biogen and Eisai ’s Aduhelm (aducanumab-avwa) for treating Alzheimer’s disease despite a negative recommendation by an AdCom. In addition to Abecma, the FDA committee also backed the use of Johnson and Johnson’s Carvykti (ciltacabtagene autoleucel, cilta-cel) to treat r/r MM. In response to both the positive decisions, Dr Gwen Nichols, chief medical officer of The Leukemia & Lymphoma Society, said: “Blood cancer is complex and patient care is highly individualised. The more safe and effective options available to oncologists and patients at all stages of their cancer, the better.” All the controversies may have impacted Abecma sales last year, with 2seventy bio forecasting the therapy to generate less than the $470m-$570m range that was previously projected. Despite the stark forecast, the therapy pulled in $472m in global sales in 2023, as per BMS’s Q4 financials. The multiple myeloma market is forecasted to generate $21.6bn in sales across the eight major pharmaceutical markets (US, France, Germany, Italy, Spain, UK, Japan, and China), as per GlobalData’s analysis . Approval as an early-line therapy may boost Abecma’s market share in the multiple myeloma indication. GlobalData is the parent company of Pharmaceutical Technology .

Dive Brief:For the first time, the Food and Drug Administration has approved a cell therapy for hard-to-treat forms of two blood cancers.Sold as Breyanzi, the therapy is now cleared for use in certain adults with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma who have received at least two prior lines of therapy. There is no established standard of care for such patients, so the FDAs decision to grant an accelerated approval provides a much-needed and potentially transformative option, according to Breyanzis developer, Bristol Myers Squibb.The FDA based its decision on results from a clinical trial that evaluated just shy of 120 participants. The trial found that at a certain dose level, around one in five people given Breyanzi had their cancer completely disappear. In total, 45% of participants responded to the therapy, and those responses lasted a median of just under three years.Dive Insight:Chronic lymphocytic leukemia and small lymphocytic lymphoma are typically slower progressing and more survivable than other cancers. In fact, treatment often isnt necessary in the early stages of the disease. Estimates hold that around 85% of people will live at least five years following a diagnosis.Yet, as these cancers progress, they may require some form of drug intervention. Usually that involves a combination of chemotherapy and targeted medicines like BTK inhibitors, a class of drugs that includes AstraZenecas Calquence and AbbVie and Johnson & Johnsons Imbruvica.For patients who dont respond or stop responding to those treatments, there are few options and poor outcomes, according to Bristol Myers. But the company believes so-called CAR-T cell therapies like Breyanzi can help solve this problem.Breyanzi is made with a patients own white blood cells, which are extracted and then shipped to a manufacturing site. There, they are engineered to better target and destroy malignant B cells that express a protein known as CD-19. The souped up blood cells are then sent back to a treatment center where they get reinfused into the patient.So far, the FDA has approved half a dozen CAR-T therapies, mostly for other blood cancers like follicular lymphoma, multiple myeloma and diffuse large B cell lymphoma. Breyanzi is now the only one indicated for chronic lymphocytic leukemia and small lymphocytic lymphoma.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, said Bryan Campbell, the commercial head of Bristol Myers cell therapy business, in a statement. But following Thursdays approval, 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.Breyanzi is cleared specifically for people who previously received a BTK blocker and a B-cell lymphoma 2 inhibitor such as AbbVie and Roches Venclexta.The FDA, in granting accelerated approval, noted that Breyanzis benefits in these cancers may need to be verified through one or more additional confirmatory studies.The agency first approved Breyanzi in 2021 as a treatment for adults with relapsed or refractory DLBCL. The drug carries a safety warning for T cell malignancies, neurological side effects, and a kind of immune system reaction called cytokine release syndrome.Editors note: this story has been updated to clarify the date on which the approval decision was issued. '

THE WOODLANDS, Texas and ST. LOUIS, March 14, 2024 /PRNewswire/ -- Cellipont Bioservices, a leading cell therapy Contract Development and Manufacturing Organization (CDMO), and Wugen, Inc., a clinical-stage biotechnology company developing allogeneic, off-the-shelf cell therapies to treat a broad range of hematological and solid tumor malignancies, today announced the signing of an agreement for the manufacturing of their CAR-T cell therapies. Continue Reading Under the agreement, Cellipont Bioservices will be providing the technology transfer and production of Wugen's allogeneic CAR-T cell therapies at their new purpose-built 76,000 sq. ft. manufacturing facility. Wugen is developing the next generation of off-the-shelf memory natural killer (NK) and CAR-T cell therapies for cancer. The company's investigational cell therapies originate from healthy donors and are further engineered to enhance their function of eliminating cancer cells. Their NK cell and CAR-T immuno-oncology therapies address the needs of patients with solid tumors, acute myeloid leukemia (AML) and T-cell malignancies. "We are excited to collaborate with Cellipont Bioservices, leveraging their expertise in cell therapy manufacturing to carry out our mission of bringing innovative CAR-T cell therapies to patients in need. This new partnership helps enable Wugen to achieve our mission to help patients with hematological malignancies with off-the-shelf cell therapies," said Kumar Srinivasan, Ph.D., MBA, president and CEO of Wugen. "We are thrilled to partner with Wugen, Inc. in advancing their groundbreaking CAR-T cell therapies. This collaboration underscores our commitment to driving innovation and accelerating the development of life-saving treatments for patients worldwide," said Edwin Beale, CCO of Cellipont. About Cellipont Cellipont Bioservices is a premier Contract Development and Manufacturing Organization (CDMO) specializing in the advancement of cell therapies. With a team of industry-leading experts, Cellipont is at the forefront of cell therapy development and manufacturing, offering comprehensive solutions from process development, analytical services, to large-scale commercial manufacturing. Our purpose-built facility, combined with our cutting-edge technology and commitment to quality enable us to support our clients in delivering life-changing cell therapies to patients worldwide. Cellipont Bioservices is dedicated to excellence in all aspects of our operations, ensuring that we not only meet but exceed the expectations of our clients and the communities we serve. To learn more, visit . About Wugen Wugen, Inc. is a clinical-stage biotechnology company developing the next generation of off-the-shelf memory natural killer (NK) and CAR-T cell therapies for cancer. Wugen is leveraging its proprietary Moneta™ platform and deep genomic engineering expertise to pioneer a new class of memory NK cell therapies to treat hematological and solid tumor malignancies. For more information, please visit . SOURCE Cellipont Bioservices