AbbVie's experimental antipsychotic drug, emraclidine, has failed to meet expectations in two mid-stage clinical trials for schizophrenia, sending ripples through the pharmaceutical industry and raising questions about the future of muscarinic receptor agonists in psychiatric treatment. The drug, a key asset acquired through AbbVie's nearly $9 billion purchase of Cerevel Therapeutics, did not demonstrate a statistically significant improvement over placebo in alleviating schizophrenia symptoms.
The news led to a sharp decline in AbbVie's stock price, with shares dropping more than 12% and erasing approximately $40 billion in market value. Analysts have expressed surprise at the results, with one describing the failure as "flat out." The outcome significantly bolsters the market position of Bristol Myers Squibb's Cobenfy (xanomeline-trospium), a competing muscarinic agonist acquired through the $14 billion acquisition of Karuna Therapeutics.
Impact on Muscarinic Antipsychotic Development
Emraclidine and Cobenfy represent a new class of antipsychotic medications designed to modulate brain chemistry by targeting muscarinic receptors. Unlike older antipsychotics that directly regulate dopamine levels, muscarinic drugs affect dopamine in a more indirect manner. Cobenfy has shown promise in clinical trials, demonstrating rapid symptom relief with fewer side effects like weight gain and sedation. An earlier, smaller study of emraclidine had also suggested clinically meaningful antipsychotic activity.
The failure of emraclidine raises concerns about the challenges of clinical trial execution in this drug class, rather than an inherent issue with the mechanism of action. Roopal Thakkar, AbbVie’s chief scientific officer, stated that the company will continue to analyze the data to determine the next steps for emraclidine.
Competitive Landscape
The setback for AbbVie has broader implications for other companies developing muscarinic antipsychotics. Neurocrine Biosciences, which recently reported mixed results for its own muscarinic drug in a schizophrenia study, saw its stock price increase following AbbVie's announcement, potentially due to reduced competitive pressure. Neumora Therapeutics, another player in the field, had previously halted a trial of its muscarinic drug due to safety concerns identified in animal studies.
Analysts suggest that Neumora may re-evaluate its muscarinic program in light of emraclidine's failure, potentially shifting focus to other assets in its central nervous system pipeline. Despite the recent setbacks, some analysts remain optimistic about the potential of muscarinic drugs for schizophrenia, emphasizing that AbbVie's results may reflect clinical trial execution risk rather than a fundamental flaw in the approach.
