Emraclidine Fails to Significantly Reduce Schizophrenia Symptoms in Phase 2 EMPOWER Trials

AbbVie announced today that emraclidine failed to bring statistically significant reductions in the positive and negative symptoms of schizophrenia in the phase 2 EMPOWER-1 and EMPOWER-2 trials.

Emraclidine, a once-daily oral monotherapy for adults, was investigated in the phase 2 EMPOWER program, for treating adults with schizophrenia experiencing an acute exacerbation of psychotic symptoms. The study aimed to evaluate multiple dosing options for emraclidine, compared with placebo, to explore the therapeutic dose range for emraclidine.

It is believed that since emraclidine is a novel M4-selective positive allosteric modulator, designed to potentially reduce excess dopamine signaling in the striatum without blocking dopamine type 2 receptors, it has the potential to reduce psychotic symptoms without leading to as many adverse events. However, in these adequately powered, placebo-controlled phase 2 trials, this drug did not meet the primary endpoint: a statistically significant reduction in the change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score compared with the placebo group at week 6.

“While we are disappointed with the results, we are continuing to analyze the data to determine next steps," said Roopal Thakkar, MD, executive vice president, research and development, chief scientific officer, AbbVie, in a statement. "We would like to extend our gratitude to the study participants and their loved ones as well as to our network of clinical investigative sites for their participation in these trials.”

In EMPOWER-1, compared with patients on placebo (n = 127) who had a Least Squares Mean difference of – 13.5, patients on emraclidine 10 mg (n = 125) and 30 mg (n = 127) had a difference of -14.7 and -16.5, respectively. In EMPOWER-2, those on placebo (n = 128) had a mean difference of -16.1, compared with -18.5 and -14.2 for those on emraclidine 15 mg and 30 mg, respectively.

Although EMPOWER-1 and EMPOWER-2 did not meet their primary endpoint, the trials demonstrated emraclidine was well-tolerated and had an adverse event profile comparable with the phase 1b trial. The most reported adverse events were headache, dry mouth, and dyspepsia.

In addition to EMPOWER-1 and EMPOWER-2, the EMPOWER program also includes a 52-week open-label extension trial called EMPOWER-3, evaluating emraclidine in patients with schizophrenia who have stable symptoms and are not currently facing acute worsening of psychotic symptoms.

“We are confident that our innovative pipeline will continue to bring meaningful therapies to patients, and we remain committed to finding better treatments for people living with psychiatric and neurological disorders,” Thakkar said.

References

^{AbbVie Provides Update on Phase 2 Results for Emraclidine in Schizophrenia. PR Newswire. November 11, 2024. https://www.prnewswire.com/news-releases/abbvie-provides-update-on-phase-2-results-for-emraclidine-in-schizophrenia-302301190.html. Accessed November 11, 2024.}