AbbVie's emraclidine, an investigational drug for schizophrenia, has failed to meet its primary endpoints in two Phase 2 clinical trials. The drug, a muscarinic M4 receptor agonist acquired as part of AbbVie's $8.7 billion acquisition of Cerevel Therapeutics, aimed to offer a novel approach to treating schizophrenia by selectively targeting M4 receptors in the central nervous system, avoiding the dopamine D2 receptor blockade common in many existing antipsychotics.
The two placebo-controlled Phase 2 studies evaluated multiple doses of once-daily emraclidine over six weeks. The primary endpoint was a reduction in the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) score from baseline compared to placebo. While AbbVie reported numerical improvements in PANSS scores with emraclidine, these changes did not reach statistical significance. The company noted that the drug was well-tolerated, with a safety profile consistent with Phase 1b testing.
Market Impact and Analysis
The failure of emraclidine poses a setback to AbbVie's ambitions in the schizophrenia market, particularly against Bristol Myers Squibb's recently approved Cobenfy (KarXT), a muscarinic M1/M4 receptor agonist. Cobenfy's approval marked the first muscarinic-receptor targeting drug to receive FDA approval for schizophrenia. Analysts have expressed concern over emraclidine's performance. Leerink Partners analyst David Risinger described the PANSS score reductions as "surprisingly low," noting they were significantly lower than those reported in Cobenfy's Phase 3 trials. Additionally, the emraclidine studies exhibited higher placebo responses compared to the Cobenfy study. The lack of dose-dependent efficacy across the multi-dose studies also raises concerns.
William Blair analysts Myles Minter and Matt Phipps called the Phase 2 results an "absolute miss," especially considering the promising Phase 1 data. They suggest that the results may indicate that both M1 and M4 agonism are necessary to achieve maximum benefit for patients, potentially solidifying Cobenfy's market position.
AbbVie's Next Steps
Despite the disappointing results, AbbVie remains committed to analyzing the data to determine the future of emraclidine, which is also being investigated in a Phase 1 trial for Alzheimer's disease psychosis. Roopal Thakkar, executive vice president, research and development, and chief scientific officer at AbbVie, stated that the company is continuing to analyze the data to determine next steps.
AbbVie's neuroscience pipeline also includes tavapadon, a drug candidate for Parkinson's disease acquired through the Cerevel acquisition, which met its primary endpoints in a Phase 3 study. Additionally, AbbVie has recently invested in psychedelic medications through a research and development alliance with Gilgamesh Pharmaceuticals and acquired Aliada Therapeutics for its Alzheimer's disease drug in early clinical development.
