BMS' newly acquired schizophrenia drug showed continued symptom improvement in open-label studies

Bristol Myers Squibb’s recently acquired schizophrenia drug demonstrated persistent symptom improvement without patients gaining weight, according to new long-term data, bolstering excitement around the prospect less than six months before the FDA will decide on its fate.

The new data from KarXT, the crown jewel in BMS’ $14 billion acquisition of Karuna Therapeutics, were presented at the Schizophrenia International Research Society annual conference in Florence, Italy. The results came from two long-term analyses of phase 3 studies called Emergent-4 and Emergent-5. 

A pooled analysis of safety data found that roughly three-quarters of patients experienced some treatment-emergent adverse event, with 14.9% experiencing a side effect that led to discontinuation. The most common side effects were nausea, vomiting and constipation.

Importantly, KarXT wasn't associated with detrimental metabolic changes, a side effect often associated with antipsychotic medications. The average change in weight over 52 weeks was a 2.6-kg reduction (about 6 pounds). More than four times as many patients lost at least 7% of their body weight than those who gained 7%. 

Roland Chen, M.D., BMS’ global head of development, did not explicitly say whether there were plans to study KarXT on top of popular GLP-1 therapies, given the potential for patients on other psychiatric medicines to be treated for associated weight gain before switching to KarXT. 

“We see KarXT as having the potential to be used in a broad set of patients who have schizophrenia,” he said. “And this would be in the context of various background therapies.” 

On efficacy, BMS found a steady increase in patients who reported at least a 30% improvement in their assessment of schizophrenia symptoms, as measured by the Positive and Negative Syndrome Scale for Schizophrenia (PANSS). The efficacy peaked at Week 44, when slightly more than 80% of patients reported at least a 30% improvement in PANSS score. The share of achieving patients dipped down to roughly 75% from Week 44 to Week 52. 

“We're seeing, on average, patients who are ending up with scores that are going to be below 70 from a baseline of 100,” he said.

Chen declined to say whether BMS planned to initiate any head-to-head trials between KarXT and second-generation antipsychotics. 

KarXT is in ongoing studies as an adjunctive schizophrenia treatment as well as a remedy for patients who have Alzheimer’s disease psychosis. Chen believes there are even more indications where the medicine could have a benefit, though he did not specify which. The FDA is slated to decide whether to approve the drug as a treatment for schizophrenia by the end of September 2024. 

The R&D executive was noncommital on plans for Karuna’s additional assets, which include KAR-2618, a phase 1-stage treatment for mood and anxiety disorders, and four preclinical assets for undisclosed indications.

“We are actively evaluating the pipeline and looking at the potential options to continue to develop in this area,” he said.