Paraproteinemias

This latest deal will aid BMS in bolstering its neuroscience portfolio. Credit: Katherine Welles / Shutterstock.com. Bristol Myers Squibb (BMS) has concluded the acquisition of biopharmaceutical company Karuna Therapeutics for $14bn in cash. The transaction was finalised following a definitive agreement signed by the companies in December 2023 . Karuna now becomes a wholly owned BMS subsidiary. The deal will boost BMS’s neuroscience portfolio. BMS has acquired Karuna’s lead asset, KarXT (xanomeline-trospium), along with its early-stage and pre-clinical pipeline. KarXT is an antipsychotic with a unique mechanism of action and a promising efficacy and safety profile. See Also: CST-2140 by CuraSen Therapeutics for Orthostatic Hypotension: Likelihood of Approval Q&A: Increasing awareness around digital therapeutics key to realising full potential The US Food and Drug Administration (FDA) recently accepted a new drug application for KarXT for the treatment of adults with schizophrenia, with an approval decision anticipated on 26 September 2025 under the Prescription Drug User Fee Act. KarXT is also undergoing registrational trials as an adjunctive therapy for schizophrenia and for treating psychosis in Alzheimer’s disease patients. Its potential for further indications such as bipolar 1 disorder and agitation in Alzheimer’s disease is being explored. Financial advisory services for the deal were provided to BMS by Gordon Dyal and Citi, with Covington & Burling offering legal counsel. Goldman Sachs acted as exclusive financial adviser to Karuna, with Simpson Thacher & Bartlett providing legal counsel. Bristol Myers Squibb CEO Chris Boerner stated: “We are excited to expand our neuroscience portfolio as we welcome Karuna to Bristol Myers Squibb. “Importantly, this transaction aligns with our commitment to strengthening BMS’s growth profile in the latter half of the decade and beyond. We look forward to working with Karuna’s talented team to bring KarXT to patients with schizophrenia later this year.” The new development comes after the FDA’s committee voted eight to three to approve BMS and 2seventy bio’s Abecma to treat relapsed or refractory multiple myeloma .

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 .

A U.S. FDA advisory committee has voted in favor of two different cell therapies — Johnson & Johnson and Legend Biotech’s Carvykti and Bristol Myers Squibb and 2seventy bio's Abecma — for earlier treatment of patients with relapsed/refractory multiple myeloma. The Oncologic Drugs Advisory Committee (ODAC) voted unanimously (11-0) in favor of Carvykti for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy including a proteasome inhibitor and an immunomodulatory agent and are refractory to lenalidomide. Carvykti, the result of a December 2017 license and collaboration agreement between J&J's Janssen Biotech and Legend Biotech, was first approved in February 2022 for the treatment of patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy. The treatment is a B-cell maturation antigen-directed genetically modified autologous chimeric antigen receptor T-cell therapy. According to Legend, a supplemental BLA supported by the CARTITUDE-4 study is currently under review by the FDA with a target PDUFA date of April 5, 2024. The ODAC also voted in favor (8-3) of Abecma for patients with triple-class exposed relapsed or refractory multiple myeloma. Abecma, jointly developed and commercialized by BMS and bluebird bio, which was spun out to create 2seventy bio, became the first cell-based gene therapy approved by the FDA for the treatment of multiple myeloma in March 2021. The drug was approved for use in adult patients with multiple myeloma who have not responded to, or whose disease has returned after, at least four prior lines (different types) of therapy. The partners' supplemental BLA seeking the expanded use of Abecma, a CAR-T cell therapy that recognizes and binds to the B-cell maturation antigen on the surface of multiple myeloma cells, originally had a PDUFA date of December 16, 2023. Back in Novembe r, the FDA delayed its decision when it decided that the ODAC would meet to discuss results from the pivotal phase 3 KarMa-3 study of Abecma in earlier lines of triple-class exposed relapsed or refractory multiple myeloma. According to BMS, the FDA has not yet assigned a new target action date for review of the sBLA. The two positive votes come in spite of FDA briefing docs that specifically noted the agency's interest in the committee's opinion on higher rates of early deaths noted in the treatment arms of Carvykti's CARTITUDE-4 trial and Abecma's KarMMa-3 trial. Earlier this year , the FDA required that manufacturers add a boxed warning to both drugs, among other CAR-T cell therapies, warning that the treatments themselves may cause cancers.