Bristol Myers Squibb Co.

With the Karuna Therapeutics takeover officially closed as of last month, Bristol Myers Squibb shared updated long-term data on Saturday for the main asset it gained through the $14-billion acquisition: experimental schizophrenia treatment KarXT (xanomeline-trospium).Bristol Myers Squibb presented one-year safety and efficacy data at the annual congress of the Schizophrenia International Research Society (SIRS), demonstrating that the dual agonist of M1 and M4 muscarinic receptors continued to improve symptoms and largely avoided some of the metabolic side effects seen with antipsychotics.The data are a welcome sight ahead of an expected September decision from the FDA. In the Phase III EMERGENT-4 open-label extension study, patients saw an average reduction of 33.3 points from baseline, as measured by the Positive and Negative Syndrome Scale (PANSS) total score, with about three-quarters achieving a greater than 30% improvement.The study enrolled 110 people with schizophrenia who had completed one of two previous five-week Phase III trials, EMERGENT-2 or EMERGENT-3; at the data cutoff, 29 participants had received KarXT for one year. Those earlier studies reported average PANSS reductions of 9.6 points and 8.4 points, respectively. Additionally, according to average patient scores on the Clinical Global Impression-Severity (CGI-S) scale, those who received KarXT shifted from “markedly ill” at baseline to “moderately” or “mildly” ill at the one-year mark.Weight loss high noteThe pharma also shared a pooled safety analysis of EMERGENT-4 along with fellow open-label, 52-week study EMERGENT-5, which combined included 718 patients who received at least one dose of KarXT, with 134 of those having taken the treatment for at least one year. According to Christoph Correll – professor of psychiatry and molecular medicine at Hofstra/Northwell’s Donald and Barbara Zucker School of Medicine and medical director in the department of psychiatry at Zucker Hillside Hospital – muscarinic receptor agonists like KarXT might have a favourable safety profile when compared with antipsychotics, which have historically led to five adverse effects that reduce quality of life: weight gain, metabolic prolactin elevation, neuromotor side effects, sexual side effects and sedation. For more, see KOL Views Q&A: Leading psychiatrist sees a muscarinic revolution coming in schizophrenia and beyond.Not only did the long-term safety data show no association between KarXT and weight gain, the treatment actually helped with weight loss. About 65% of patients experienced an overall reduction in weight, and those who completed one year of treatment saw an average loss of 2.6kg.“It is promising to see that over one year of treatment, KarXT was not associated with burdensome side effects, specifically weight gain and metabolic dysfunction, as well as extrapyramidal symptoms, which underscores its potential to provide a meaningful and differentiated option for people living with schizophrenia,” said Roland Chen, head of immunology, cardiovascular and neuroscience development at Bristol Myers Squibb.

Fresh off closing its $14 billion acquisition of Karuna Therapeutics a few weeks ago, Bristol Myers Squibb is presenting long-term data for its new subsidiary’s promising schizophrenia drug, known as KarXT. Bristol Myers said KarXT’s efficacy was maintained through one year in an open-label extension, presenting the data Saturday at the Schizophrenia International Research Society congress. Additionally, more than 75% of patients who continued taking the drug for a year achieved a “clinically meaningful” result, BMS senior VP of global drug development Roland Chen told Endpoints News . You’ll get access to free articles each month, plus you can customize what newsletters get delivered to your inbox each week, including breaking news.

The FDA has expanded the label for Johnson & Johnson and Legend Biotech's Carvykti (ciltacabtagene autoleucel) to make it a treatment option for multiple myeloma patients after just one prior line of therapy.The decision, which follows a recent positive vote from an FDA advisory committee, allows the BCMA-targeting CAR-T cell therapy to be prescribed much sooner in the treatment paradigm, compared to its initial approval back in 2022 when it was cleared for fifth-line use.Carvykti's latest win comes on the heels of the FDA approving CAR-T rival Abecma (idecabtagene vicleucel), co-developed by Bristol Myers Squibb and 2seventy bio, in the third-line setting for relapsed or refractory multiple myeloma.Johnson & Johnson's supplemental filing was supported by the Phase III CARTITUDE-4 study, which evaluated Carvykti versus standard regimens in adults with relapsed and lenalidomide-refractory multiple myeloma who had received one to three prior lines of therapy. Carvykti reduced the risk of disease progression or death by 59% compared to standard regimens, meeting the primary endpoint.Meanwhile, an interim analysis done at the November 2022 cutoff showed a benefit of 22% with Carvykti on the key secondary measure of overall survival (OS). According to briefing documents released by the FDA last month, that rate improved to 43% by December 2023 when half of the 250 planned OS events needed for the final analysis had occurred.Label details early deathsLike Abecma, Carvykti's warning label details an imbalance in early deaths in its pivotal study. Within the first 10 months of randomisation of CARTITUDE-4, 14% of patients in the Carvykti arm experienced early deaths, compared to 12% for controls. Among the 29 early deaths with Carvykti, 10 occurred before infusion, all due to disease progression, while 19 occurred after infusion, with 3 due to disease progression and 16 due to adverse events, mainly infections.The drug's boxed warning was also updated to include secondary haematological malignancies, following a request by the FDA earlier this year that affected CAR-Ts as a class.Tyrone Brewer, president of US haematology at Johnson & Johnson Innovative Medicine, said the company has been ramping up efforts to boost supplies. "We more than doubled manufacturing of Carvykti in 2023, we are striving to double again in 2024, and we will continue to invest in our capacity."