Tavapadon

AbbVie lost about $40 billion in market value Monday morning after an experimental drug the company had bet heavily on failed two important clinical trials.The drug, called emraclidine, was developed by Pfizer spinout Cerevel Therapeutics, which AbbVie recently acquired for almost $9 billion. Its one of a new class of brain-balancing medications researchers see as valuable tools for treating a variety of psychiatric conditions. With emraclidine, Cerevel chose schizophrenia as the first target, and over the past couple of years has been running a pair of studies to assess whether the drug can quickly alleviate symptoms of the disorder.AbbVie has now disclosed the studies did not succeed. Three doses of the drug were tested, and neither performed significantly better than a placebo after six weeks of treatment. The trials together enrolled around 750 participants, and evaluated them with a well-known scale used to measure the different symptoms people with schizophrenia experience, from positive ones like excitement and hallucinations to negative ones like emotional withdrawal.“While we are disappointed with the results, we are continuing to analyze the data to determine next steps,“ said Roopal Thakkar, AbbVies chief scientific officer,in the companys statement.The Illinois-based pharmaceutical giant said neuroscience remains one of its key focus areas. Just last month, AbbVie announced plans to spend $1.4 billion buying a startup with an experimental treatment for Alzheimers disease.The company also noted how it gained an entire pipeline of drug programs from the Cerevel acquisition, with multiple clinical-stage and preclinical candidates that complement its existing portfolio of brain medicines. Net revenue from that portfolio, which includes Botox, the antipsychotic Vraylar and the migraine medication Ubrelvy, totaled almost $6.5 billion over the first nine months of this year.One such Cerevel drug, a Parkinsons treatment called tavapadon, defied analyst expectations by succeeding in a late-stage trial earlier this year.Still, AbbVie investors may not see much of a silver lining. Company shares were down more than 12% Monday morning, representing one of the largest single-day dips involving a big pharma stock over the past year.This is disappointing and unexpected, wrote Louise Chen, an analyst at the investment firm Cantor Fitzgerald, in a note to clients.In an earlier, much smaller schizophrenia trial, researchers found two doses of emraclidine each beat a placebo at reducing scores on the same symptoms scale used in the Phase 2 studies.Additionally, emraclidine works in a similar way to Cobenfy, an antipsychotic medication that succeeded in three medium- to large-sized clinical trials before receiving Food and Drug Administration approval in September. Less than three weeks after AbbVie announced its Cerevel acquisition, Bristol Myers Squibb agreed to buy Cobenfys developer, Karuna Therapeutics, for $14 billion.Schizophrenia patients switch medications often, either because they carry side effects like weight gain or because they arent properly controlling the disease. Clinical testing of Cobenfy showed it doesnt cause some of the more challenging side effects seen with other antipsychotics. That, plus Cobenfys ability to act quickly, has led both Bristol Myers and Wall Street analysts to expect billions of dollars in peak annual sales from the drug.Shares of Bristol Myers were up almost 12% late Monday morning.Olivia Brayer, an analyst at Cantor who covers the company, argues that emraclidines failure removes a major overhang for Cobenfy, as its biggest competitive threat in schizophrenia is no longer.The Cerevel acquisition just went up in flames, Brayer wrote in a note to clients, adding that her team has been getting questions about how Bristol Myers stock could move based on the results of AbbVies two studies. But an outright failure wasn't on anyone's bingo card. '

An AbbVie schizophrenia drug acquired as part of a multi-billion dollar deal has failed two mid-stage studies, dealing a setback to the company’s plans to compete with a Bristol Myers Squibb medication that was recently approved in schizophrenia and is projected to become a blockbuster seller across several psychiatric indications. The preliminary results announced Monday are from two placebo-controlled Phase 2 studies designed to evaluate multiple doses of emraclidine, a once-daily drug, over the course of six weeks. The main goal was to show 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 used to assess schizophrenia symptoms. AbbVie said both studies show the experimental drug achieved numerical improvements in score compared to a placebo, but the changes were not enough to be statistically significant. The company added that the drug was well tolerated with a safety profile comparable to what was observed in Phase 1b testing. Many currently available schizophrenia drugs work by blocking dopamine type 2 (D2) receptors. But these drugs offer limited efficacy while introducing side effects that make it hard for patients to stay on treatment. Drug developers have been looking for other targets. Emraclidine gave AbbVie entry into a group of companies developing drugs targeting muscarinic receptors, which are receptors in the central nervous system that play key roles in neuronal functions. Emraclidine is an agonist of the muscarinic acetylcholine receptor type 4, or M4 receptor. By selectively targeting and activating this receptor, the drug is intended to treat schizophrenia in a way that does not hit D2 receptors. Sponsored Post The Funding Model for Cancer Innovation is Broken — We Can Fix It Closing cancer health equity gaps require medical breakthroughs made possible by new funding approaches. By Eve McDavid - CEO of Mission-Driven Tech Emraclidine was initially developed by Cerevel Therapeutics, which had advanced the drug to the Phase 2 studies EMPOWER 1 and EMPOWER 2 when AbbVie reached an $8.7 billion deal to acquire the biotech late last year. Weeks after that announcement, BMS announced a $14 billion deal to buy Karuna Therapeutics, whose M1- and M4-targeting schizophrenia drug was already under FDA review. The September approval of that twice-daily pill, now named Cobenfy, made it the first muscarinic-receptor targeting drug to pass the FDA’s regulatory bar. Though emraclidine trailed the BMS product, AbbVie hoped to offer better safety and more convenience with once-daily dosing. Now AbbVie must figure out how to proceed with emraclidine, which is also in Phase 1 testing in Alzheimer’s disease psychosis. “While we are disappointed with the results, we are continuing 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 Monday, Leerink Partners analyst David Risinger described emraclidine’s PANSS scores as “surprisingly low.” Looking across trials, he noted that the AbbVie drug’s reduction in score was significantly lower than what was reported for Cobenfy’s Phase 3 test. The AbbVie drug’s studies also had higher placebo responses compared to the placebo group in the BMS drug’s study. Risinger added that emraclidine’s failure to show dose-dependent efficacy across the multi-dose studies is concerning. William Blair analysts Myles Minter and Matt Phipps said the “absolute miss” of emraclidine in Phase 2 is a surprise, given the strength of the drug’s Phase 1 data. The failure all but removes a multi-billion dollar product from the AbbVie pipeline and calls into question the $8.7 billion Cerevel acquisition, they said. Sponsored Post The Future of Hospitals and Pharma Companies Will Depend on Strength of Healthcare Analytics Insights PurpleLab® stands out from others in this sector by providing its data analytics services to several different groups of users across healthcare and pharma companies. By Stephanie Baum “While additional details are necessary to fully understand the EMPOWER study outcomes, the results may suggest M1 and M4 agonism are needed to drive maximum benefit for patients, expanding Cobenfy’s first-mover advantage and ultimate market opportunity,” Minter and Phipps wrote. Despite emraclidine’s disappointing Phase 2 results in schizophrenia, AbbVie still has more shots on goal from its Cerevel acquisition and from other deals. This past April, Cerevel reported its drug candidate tavapadon met the main goals of its Phase 3 study in Parkinson’s disease. In May, AbbVie paid startup Gilgamesh $65 million up front to begin an R&D alliance focused on psychedelic medications for diseases and targets that were not disclosed.