AbbVie's emraclidine, a key asset acquired through the Cerevel Therapeutics acquisition, has failed to meet its primary endpoint in two Phase II clinical trials for schizophrenia. The drug did not show a statistically significant improvement in symptoms compared to placebo, leading to a significant drop in AbbVie's stock price.
Trial Results and Market Reaction
The EMPOWER program, designed to evaluate emraclidine in patients experiencing acute exacerbation of schizophrenia, yielded disappointing results. The primary endpoint, change from baseline on the Positive and Negative Syndrome Scale (PANSS) at week six, was not met in either the EMPOWER-1 or EMPOWER-2 studies. In EMPOWER-1, emraclidine's score was slightly higher than placebo for both doses, while in EMPOWER-2, the lower dose showed an increase in the score, indicating a worsening of symptoms. None of these results were statistically significant.
Following the announcement, AbbVie's shares plummeted 12%, reflecting investor concerns about the future of AbbVie's neuroscience strategy. Analysts expressed surprise at the failure, especially given the initial promise of emraclidine. Stifel analysts noted the unexpectedly high placebo response in both studies, while BMO Capital Markets cautioned against solely attributing the failure to the placebo effect.
Strategic Implications for AbbVie
The failure of emraclidine poses questions about AbbVie's long-term growth outlook, particularly in light of upcoming patent expirations. Guggenheim Securities suggests a potential 3% drop in AbbVie's shares due to the removal of emraclidine's projected sales, which were previously estimated to reach $1.5 billion by 2033. The company is now expected to focus on its internal R&D efforts and external business development to secure additional growth drivers. AbbVie is also looking to the remaining pipeline from the Cerevel deal, such as Tavapadon, which recently met the primary endpoint in a Phase III trial for Parkinson’s disease.
Competitive Landscape
Bristol Myers Squibb (BMS) stands to benefit from AbbVie's setback. BMS's recently approved Cobenfy (previously known as KarXT), acquired through the Karuna Therapeutics acquisition, now faces less near-term competition in the schizophrenia market. Truist Securities predicts that peak sales for Cobenfy could reach $4 billion.
Emraclidine and Cobenfy both target muscarinic receptors, but with different specificities. Emraclidine selectively targets the M4 receptor, while Cobenfy targets both M1 and M4 receptors. Stifel analysts suggest that the M1 receptor may contribute to cognitive efficacy, potentially explaining the difference in outcomes between the two drugs.
Broader Implications for CNS Drug Development
The failure of emraclidine serves as a reminder of the challenges inherent in CNS drug development. Despite recent successes in neuroscience, including approvals in Alzheimer's disease and postpartum depression, the CNS remains a high-risk area. Stifel analysts suggest that the emraclidine failure may make investors more cautious about Phase II CNS studies and their ability to de-risk Phase III trials.
