AbbVie's emraclidine, an oral monotherapy, failed to demonstrate a statistically significant reduction in schizophrenia symptoms compared to placebo in two Phase II clinical trials, EMPOWER-1 and EMPOWER-2. The trials assessed the efficacy of emraclidine in patients experiencing an acute exacerbation of schizophrenia, with the primary endpoint being the change in Positive and Negative Syndrome Scale (PANSS) total scores at six weeks.
EMPOWER Trial Results
The EMPOWER program included two placebo-controlled Phase II trials (EMPOWER-1 and EMPOWER-2) and one 52-week open-label extension trial (EMPOWER-3). The primary endpoint was the reduction of symptoms as measured by PANSS total scores. In EMPOWER-1, the placebo group showed an 8.16-point change, while the 10 mg and 30 mg emraclidine groups showed changes of 7.65 and 7.89 points, respectively. Similarly, in EMPOWER-2, the placebo group had an 8.22-point change, with the 10 mg and 30 mg emraclidine groups showing 8.49 and 7.75-point changes, respectively. These results indicate that emraclidine did not outperform placebo in reducing schizophrenia symptoms.
Safety and Tolerability
Despite not meeting the primary endpoint, emraclidine exhibited a tolerable safety profile, consistent with Phase Ib findings. Common adverse events (AEs) reported across all treatment groups included headache, dry mouth, and dyspepsia, with comparable rates between the emraclidine and placebo groups. This suggests that emraclidine is generally well-tolerated, even though it did not demonstrate significant efficacy in these trials.
Schizophrenia Disease Burden
Schizophrenia affects approximately 24 million people worldwide, or one in 222 adults, according to the World Health Organization (WHO). Onset typically occurs during adolescence or early adulthood, with men often experiencing symptoms earlier than women. A significant proportion of individuals with schizophrenia do not receive adequate mental health care; WHO estimates suggest that only about 31.3% of people with psychosis receive specialist mental health care.
In the United States, an estimated 2.8 million adults over the age of 18 were affected by schizophrenia in 2020, with approximately 40% remaining untreated, according to the Treatment Advocacy Center. The National Alliance on Mental Illness (NAMI) estimates the prevalence in the U.S. to be between 0.25% and 0.64%. Schizophrenia is often accompanied by other mental health conditions, such as major depressive disorder, post-traumatic stress disorder, obsessive-compulsive disorder, and substance abuse disorders.
Future Directions
AbbVie intends to further analyze the data from the EMPOWER trials to determine the next steps for emraclidine. "While we are disappointed with the results, we are continuing to analyze the data to determine next steps," said Roopal Thakkar, MD, EVP, research and development, chief scientific officer, AbbVie. The company remains committed to developing innovative therapies for psychiatric and neurological disorders.
