Cerevel Therapeutics LLC

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.

Axonis Therapeutics, a young biotechnology company, has raised $115 million to support its efforts to make first-of-their-kind medicines for neurological disorders.The investment firms Cormorant Asset Management and venBio Partners co-led the Series A financing round announced Wednesday. According to Axonis, the round also had significant contributions from a handful of other backers, including Sofinnova Investments and Perceptive Advisors, and attracted more interest than initially expected.The fresh funds will be used to push Axonis most advanced drug through key experiments designed to validate the underlying idea behind it and show it works as intended in people. The drug, which should enter human testing this year,is meant to treat epilepsy and pain by amplifying KCC2, a protein vital for brain function.In addition to that program, Axonis plans to put money toward next generation compounds directed at KCC2 for epilepsy, pain, as well as other psychiatric and neurodevelopmental disorders.In the nervous system, cells communicate via the rush of electrically charged particles. The cascade is essential for the body to function. It tells muscles how to move and the brain what its sensing from the sound of a morning alarm to the smell of coffee.But its a complex and delicate balance. If this stream of particles, or ions, happens too often or not enough, it can cause disease. Researchers have found overactive brain cells in people with Alzheimers and those with depression who dont respond to popular medications. Overly excited cells are also a hallmark of epileptic conditions.Axonis and its principle backers think the company has identified a very promising target in KCC2, which regulates two signaling molecules that calm nerve cells.We like the target and the preclinical data and the market opportunities, said Raymond Kelleher, a managing director at Cormorant.Kelleher explained that, when Cormorant chose to invest in Axonis, the firm was struck by the logic of Axonis strategy. KCC2 is in the right place to regulate nerve cell excitement in a way that can suppress seizures, he said. Theres also genetic evidence supporting its use as a target, since rare mutations in the protein are tied to certain childhood epilepsies.More broadly, Kelleher believes investors are waking up to the progress biotechs have made developing more precise drugs for the central nervous system. Karuna Therapeutics and Cerevel Therapeutics, for example, were recently acquired for $14 billion and almost $9 billion. Their work on a new class of schizophrenia medication has brought attention back to the largely overlooked field of neuropsychiatry.A wave of startups have drummed up excitement as well. One, named Rapport Therapeutics, raised $136 million in June by going public. Like Axonis, the company is trying to create targeted neurological treatments, with its most advanced program in early human testing as a potential therapy for drug-resistant seizure disorders.Rapport was backed early on by Johnson & Johnson, Third Rock Ventures and Arch Venture Partners, and later by Cormorant.We like the direction that the CNS field is moving in, Kelleher said. Investors and strategics are definitely taking interest.Axonis was co-founded in 2019 by Joanna Stanicka, a former research fellow at Harvard Medical School, and Corey Goodman, who also co-founded venBio and currently serves as one of the firms managing partners. Ahead of the Series A round, Axonis had raised more than $34 million in dilutive seed funding.Alongside its new haul, the company has added Kelleher and Jonathan Leff, an executive partner at Sofinnova, to its board of directors. '

People with advanced Parkinsons disease have a new treatment option, as the Food and Drug Administration on Thursday approved a combination therapy from AbbVie thats designed to provide longer-lasting movement control.Parkinsons is hallmarked by unintentional muscle movements like shaking or stiffness the result of nerve cells progressively breaking down and dying. Two drugs, carbidopa and levodopa, have become mainstay treatments for the motor symptoms associated with the disease. AbbVies now-approved Vyalev pairs these medications together, but in a unique way.Vyalev uses prodrug versions of carbidopa and levodopa, meaning their therapeutic effects arent felt until theyre metabolized. Additionally, Vyalev is the first and only levodopa-based therapy given as a 24-hour infusion, similar to an insulin pump. That could be particularly useful for people with advanced Parkinsons, who often have trouble swallowing pills because of their impaired motor function.Due to the progressive nature of the disease, oral medications are eventually no longer as effective at motor symptom control and surgical treatment may be required,“ said Robert Hauser, director of the Parkinson's and Movement Disorder Center at the University of South Florida, in a statement from AbbVie.“This new, non-surgical regimen provides continuous delivery of levodopa morning, day and night, added Hauser, who has received research funding and consulting fees from the company.AbbVie originally asked the FDA for approval more than two years ago. But twice since then, the agency has knocked back the companys request. The first time, it wanted more information about the pump used to administer Vyalev. The second, it had problems with a third-party manufacturer listed in the approval application. AbbVie said issues at that facility did not involve Vyalev or any of the companys other medicines.With those problems apparently addressed, the FDA granted approval based on results from two late-stage clinical trials. One enrolled 174 participants with advanced Parkinsons and compared Vyalev to treatment with an oral, fast-acting tablet of levodopa and carbidopa. It showed those on AbbVies drug experienced superior improvement in their motor fluctuations and more time with their symptoms in check.The other trial had a yearlong study period, during which all participants received Vyalev and knew they were on that drug.Now post-approval, AbbVie said patient access to Vyalev will depend on individual insurance plans. Coverage for patients on Medicare, meanwhile, is expected in the second half of 2025, according to the company.AbbVie previously estimated that peak annual sales of the drug could surpass $1 billion.Vyalevs clearance is the second victory for AbbVie in Parkinsons this year. In April, a medicine the company got through its nearly $9 billion acquisition of Cerevel Therapeutics delivered surprisingly strong results in a late-stage study. Researchers found the drug, called tavapadon, was better than a placebo at helping to suppress motor fluctuations and extending the time symptoms were under control. '