AbbVie's investigational antipsychotic drug, emraclidine, has failed to meet its primary endpoints in two Phase II clinical trials, EMPOWER-1 and EMPOWER-2, designed to evaluate its efficacy in treating schizophrenia. The announcement led to a significant drop in AbbVie's stock price, plummeting over 12%. This setback highlights the challenges in developing new treatments for psychiatric disorders and underscores the high-risk nature of pharmaceutical research and development.
The EMPOWER trials were randomized, double-blind, placebo-controlled studies assessing emraclidine as a once-daily, oral monotherapy in patients experiencing an acute exacerbation of psychotic symptoms. EMPOWER-1 (NCT05227690) evaluated 10mg and 30mg doses, while EMPOWER-2 (NCT05227703) tested 15mg and 30mg doses. A total of 372 patients were enrolled across both trials.
The primary endpoint for both trials was the reduction in the Positive and Negative Syndrome Scale (PANSS) total score. In EMPOWER-1, the PANSS scores were -14.7 (10mg) and -16 points (30mg) versus -13.5 in the placebo arm. In EMPOWER-2, the PANSS scores were -18.5 (15mg) and -14.2 (30mg) versus -16.1 in the placebo arm. These results indicated that emraclidine did not demonstrate a statistically significant improvement compared to placebo in either trial.
AbbVie's Response and Future Steps
Roopal Thakkar, AbbVie’s executive vice president of research and development and chief scientific officer, stated, "While we are disappointed with the results, we are continuing to analyse the data to determine next steps." AbbVie acquired emraclidine through its $8.7 billion acquisition of Cerevel Therapeutics in August 2024. Emraclidine is a potential novel M4-selective positive allosteric modulator (PAM).
Contrasting Fortunes: Bristol Myers Squibb and KarXT
In contrast to AbbVie's disappointing results, Bristol Myers Squibb (BMS) is experiencing positive momentum with its schizophrenia treatment, KarXT (xanomeline-trospium). BMS acquired KarXT through its $14 billion acquisition of Karuna Therapeutics in December 2023. KarXT features a novel mechanism of action and differentiated efficacy and safety profile.
Recent data from a Phase III schizophrenia trial showed that KarXT met its primary endpoint, demonstrating a significant 9.2-point reduction in the PANSS total score compared to placebo at week five. Following AbbVie's announcement, BMS's stock price rose by over 11%.
Market Projections
GlobalData’s expiry model forecasts KarXT to reach an annual total of $2.81 billion in US sales by 2033. The US Food and Drug Administration (FDA) has accepted Karuna’s New Drug Application (NDA) for KarXT for the treatment of schizophrenia in adults.
