The acquisition of Karuna Therapeutics Inc. by Bristol Myers Squibb Co. (BMS) was announced in December 2023, and closed as the BioEurope Spring meeting was convening in March. Along with the acquisition of Cerevel Therapeutics Inc. by Abbvie Inc., the deal signaled that big pharma companies were ready to get back into the brain diseases space.
The FDA has approved Cobenfy, a dual M1/M4 muscarinic agonist that offers a fundamentally different approach to treating schizophrenia. The fixed dose combination of xanomeline-trospium is the first to act via a novel mechanism for the serious psychiatric disorder in over 50 years, finally expanding the treatment options beyond dopamine-targeted therapies. Bristol Myers Squibb Co., which acquired Cobenfy developer Karuna Therapeutics Inc. for $14 billion in a deal that closed in March 2024, said the drug will be available in the U.S. from late October.
Nine years on from securing $3.84 million for a phase I clinical trial to test the formulation, with results showing it overcame side effects that had confounded its forerunner, the schizophrenia treatment Karxt met its PDUFA date Sept. 26 with no decision by midday. If approved, the fixed combination of xanomeline-trospium will be the first in a new drug class, and as a dual M1/M4 muscarinic agonist, the first new therapy to act via a novel mechanism for the serious psychiatric disorder in over 50 years.
Adam Lenkowsky, chief commercial officer for Bristol Myers Squibb Co. (BMS), said his firm plans to launch Karxt (xanomeline-trospium) in the U.S. as soon as it’s approved by the U.S. FDA, and “expect[s] to accumulate sales in early 2025.” BMS tied a bow on the year by disclosing its plan to pay $330 per share to take over Karuna Therapeutics Inc. in a deal valued at $14 billion to bring aboard Karxt, which acts as a dual M1/M4 muscarinic acetylcholine receptor agonist. The FDA has assigned Sept. 26, 2024, as the PDUFA date for Karxt as a new treatment for schizophrenia in adults.
The pivotal phase III study of brilaroxazine from Reviva Pharmaceuticals Holdings Inc. for adults with schizophrenia hit its primary endpoint and two key secondary endpoints, following positive phase II data in 2021. The serotonin-dopamine signaling modulator, the company’s lead candidate, is a once-daily treatment. Results from the study showed brilaroxazine demonstrated reductions in all major symptom domains for the patients and the secondary endpoints at week 4 when comparing the 50-mg dose with placebo.
In a race with Karuna Therapeutics Inc. to get its schizophrenia drug to market, Cerevel Therapeutics Holdings Inc. has priced an underwritten public offering at $22.81 per share. The offering is worth of about $450 million, with the company estimating sales of the 19.7 million shares will yield net proceeds of about $433.6 million.
Just days after Karuna Therapeutics Inc. reported positive data from a third registrational trial of Karxt (xanomeline plus trospium) in schizophrenia, Puretech Health plc sold a portion of its royalty in Karxt in a potential $500 million agreement with Royalty Pharma. Puretech was a founder of Karuna and co-inventor of Karxt, an oral M1/M4-preferring muscarinic agonist.
With phase III data in hand from the Emergent-3 study of Karxt (xanomeline plus trospium) in adults with schizophrenia, Karuna Therapeutics Inc. continues to target mid-2023 for an NDA submission to the U.S. FDA. The 256-subject trial met its primary endpoint, with Karxt turning up a statistically significant and clinically meaningful 8.4-point reduction in Positive and Negative Syndrome Scale total score compared to placebo at the fifth week.
Alkermes plc’s recent update on sales of the schizophrenia drug Lybalvi (also indicated for bipolar I disorder) along with positive phase III data from Karuna Therapeutics Inc. from tests of Karxt (xanomeline plus trospium) shone more light on the troublesome indication, where Cerevel Therapeutics Holdings Inc. is advancing emraclidine in what could be a registrational phase II study.
Shares in Karuna Therapeutics Inc. soared Aug. 8 as the biotech moved closer to a breakthrough for schizophrenia therapy after its potential first-in-class drug Karxt (xanomeline + trospium) met its goals in a closely watched phase III trial. Analysts said results from the Emergent-2 trial were at the top end of what was expected, lifting Karuna’s shares (NASDAQ:KRTX) 71.8% to a 52-week high of $241.19.
