FDA Approves the Oral Medication KarXT for Schizophrenia

The FDA has approved Cobenfy (xanomeline and trospium chloride), an oral medication to treat adults with schizophrenia.

Schizophrenia can cause psychotic symptoms including hallucinations (such as hearing voices), difficulty controlling one’s thoughts and being suspicious of others. It affects about 1% of Americans.

“For people living with schizophrenia, it's often difficult to find a treatment that works for them. Having a variety of treatment options gives patients and healthcare providers the tools to help manage this serious condition,” Gordon Lavigne, CEO of the Schizophrenia & Psychosis Action Alliance, said in a news release.

Developed by Karuna Therapeutics, Cobenfy is a new approach to treating schizophrenia by selectively targeting M 1 and M 4 receptors in the brain without blocking D 2 receptors. Bristol Myers Squibb acquired Karuna in December 2023 for about $14 billion.

All other treatments for schizophrenia work by targeting dopamine receptors, Dr Robert McCutcheon, Wellcome Clinical Research Career Development Fellow, Department of Psychiatry, University of Oxford, said in a separate statement. “This is the first treatment that has a different target. We hope this may mean it can help people who don’t respond to standard treatments and maybe help the symptoms that aren’t helped by existing treatments.”

Cobenfy is expected to available in October 2024. Bristol Myers Squib has also launched the Cobenfy Cares program to assist patients with access.

Cobenfy will cost about $1,850 for a month’s supply or $22,500, according to media reports. This priced just above what the Institute for Clinical and Economic Review (ICER) indicated would be a cost-effective price. In a final evidence report issued in March 2024, ICER indicate the drug would achieve common thresholds for cost-effectiveness if priced between $16,000 to $20,000 per year.

The FDA approval is based on data from the EMERGENT clinical program, which includes three placebo-controlled efficacy and safety trials and two open-label trials. In the phase 3 EMERGENT-2 and EMERGENT-3 trials, Cobenfy met its primary endpoint, demonstrating statistically significant reductions of schizophrenia symptoms.

Cobenfy demonstrated a 9.6-point reduction in the Positive and Negative Syndrome Scale (PANSS) total score compared with placebo at week five. Additionally, in EMERGENT-2, Cobenfy demonstrated a statistically significant improvement in illness measured by the Clinical Global Impression-Severity (CGI-S) score, a secondary endpoint in the trial.

The most common adverse reactions were nausea, dyspepsia, constipation, vomiting, hypertension, abdominal pain, diarrhea, tachycardia, dizziness and gastroesophageal reflux disease. Cobenfy does not have atypical antipsychotic class warnings and precautions and does not have a boxed warning.