AbbVie drug expected to compete with Bristol Myers’ new schizophrenia drug fails Phase 2 test

An AbbVie schizophrenia drug acquired in a multibillion-dollar deal failed two mid-stage trials, dealing a setback to the company’s plans to compete with a Bristol Myers Squibb drug recently approved for schizophrenia and a Blockbuster is intended to become a seller for various psychiatric indications.

The preliminary results announced Monday come from two placebo-controlled Phase 2 trials that examined multiple doses of emraclidine, a once-daily drug, over six weeks. The primary objective was to demonstrate a reduction in score from baseline (a lower score indicates improvement) compared to placebo, according to the Positive and Negative Syndrome Scale for Schizophrenia (PANSS), a rating scale for assessing schizophrenia symptoms. AbbVie said both studies showed the experimental drug produced numerical improvements in scores compared to a placebo, but the changes were not enough to be statistically significant. The company added that the drug was well tolerated and had a safety profile comparable to that observed in Phase 1b testing.

Many currently available schizophrenia medications work by blocking dopamine type 2 (D2) receptors. However, these drugs offer limited effectiveness but bring side effects that make it difficult for patients to continue treatment. Drug developers have looked for other targets. Emraclidine gave AbbVie entry into a group of companies developing drugs that target muscarinic receptors. These are receptors in the central nervous system that play a key role in neuronal functions. Emraclidine is an agonist of the muscarinic acetylcholine receptor type 4 or M4 receptor. By targeting and activating this receptor, the drug is intended to treat schizophrenia in a way that does not attack D2 receptors.

Emraclidine was originally developed by Cerevel Therapeutics, which had advanced the drug into Phase 2 EMPOWER 1 and EMPOWER 2 trials when AbbVie closed an $8.7 billion deal to acquire the biotech late last year. Weeks after that announcement, BMS announced a $14 billion deal to purchase Karuna Therapeutics, whose schizophrenia drug targeting M1 and M4 was already under FDA review. The approval in September of this twice-daily pill, now called Cobenfy, made it the first drug targeting muscarinic receptors to pass the FDA approval standard. Although emraclidine succeeded the BMS product, AbbVie hoped to provide greater safety and convenience with once-daily dosing. Now AbbVie has to figure out what happens next with emraclidine, which is also in Phase 1 trial for the treatment of Alzheimer’s psychosis.

“While we are disappointed with the results, we continue to analyze the data to determine next steps,” Roopal Thakkar, executive vice president, research and development, chief scientific officer, AbbVie, said in a prepared statement.

In a note sent to investors on Monday, Leerink Partners analyst David Risinger described Emraclidine’s PANSS scores as “surprisingly low.” Looking at all the studies, he found that the AbbVie drug’s rating reduction was significantly smaller than that reported for Cobenfy’s Phase 3 trial. The AbbVie drug trials also showed higher placebo responses compared to the placebo group in the BMS drug trial. Risinger added that the lack of dose-dependent efficacy of emraclidine in the multiple-dose studies was concerning.

William Blair analysts Myles Minter and Matt Phipps said emraclidine’s “absolute failure” in Phase 2 was a surprise given the strength of the drug’s Phase 1 data. The failure nearly removes a multibillion-dollar product from AbbVie’s pipeline and calls into question its $8.7 billion acquisition of Cerevel, they said.

“While additional details are required to fully understand the results of the EMPOWER trial, the results may indicate that M1 and M4 agonism are required to achieve maximum patient benefit and Cobenfy’s first-mover advantage and expand ultimate market opportunities,” Minter and Phipps wrote.

Despite emraclidine’s disappointing Phase 2 results in schizophrenia, AbbVie still has more shots on goal through the Cerevel acquisition and other deals. Last April, Cerevel reported that its drug candidate tavapadone met the key objectives of its Phase 3 trial in Parkinson’s disease. In May, AbbVie paid startup Gilgamesh $65 million up front to create a research and development alliance focused on psychedelic drugs for diseases and targets that were undisclosed.