An experimental Parkinson’s disease drug on its way to AbbVie as part of an $8.7 billion acquisition has met the goals of a pivotal study, setting up the pharmaceutical giant with a drug prospect that could be ready for regulatory submissions after the deal’s close, expected later this year.
According to the preliminary results reported Thursday by the drug’s developer, Cambridge, Massachusetts-based Cerevel Therapeutics, treatment with tavapadon led to a longer time during which Parkinson’s motor symptoms were controlled. Patients who received the Cerevel drug experienced a statistically significant increase in this total “on” time, the company said.
In Parkinson’s, patients lack sufficient levels of dopamine, a neurotransmitter that plays a role in regulating muscle movement. Standard treatment is levodopa, a drug that converts to dopamine in the body. Other available treatments include dopamine agonists, drugs that activate dopamine receptors in the brain. Cerevel’s tavapadon is a small molecule designed to selectively target the D1 and D5 receptors, avoiding other dopamine receptors that can trigger side effects. Furthermore, the once-daily oral drug is a partial agonist, which the company contends activates its target receptors in a way that achieves a balance of motor control, safety, and tolerability. Cerevel claims tavapadon is the first and only selective D1/D5 partial agonist in development for Parkinson’s.
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The Phase 3 study enrolled 507 adults with a confirmed Parkinson’s diagnosis. These study participants experienced motor fluctuations and were receiving levodopa for at least four weeks prior to screening. Patients in the 27-week trial were randomly assigned to receive either the Cerevel drug and levodopa or a placebo and levodopa. The main goal was to measure the change from baseline in total “on” time without involuntary troublesome dyskinesia, or involuntary muscle movements. Secondary goals included measuring the “off” time when motor symptoms reappear.
Cerevel reported that the study drug arm showed a 1.7 hour increase in “on” time versus a 0.6 hour increase in the placebo group, results that were both statistically significant and clinically meaningful. On the key secondary goal measuring “off” time, the company said the reduction in the tavapadon arm was also statistically significant. Cerevel said tavapadon was generally well tolerated by patients in the study, adding that the drug’s safety profile was consistent with prior clinical trials. The majority of adverse events reported were characterized as mild to moderate in severity.
Full Phase 3 results will be submitted for presentation at future medical meetings, Cerevel said. The results will also support regulatory submissions of the drug. Two additional ongoing Phase 3 clinical trials are evaluating tavapadon as a monotherapy. Cerevel expects to report preliminary data from these studies in the second half of this year. The trial results so far demonstrate that the Cerevel drug has the potential to offer a new treatment option for Parkinson’s patients, according to Hubert Fernandez, global principal investigator in the tavapadon studies and the James and Constance Brown endowed chair in movement disorders, professor of neurology, and director at the Center for Neurological Restoration at Cleveland Clinic.
“Parkinson’s disease is the fastest growing neurodegenerative disorder in the world, and a significant need exists for a new treatment option that provides the right balance of dopamine signaling and delivers sustained motor control without the burdensome side effects associated with current treatments,” Fernandez said in a prepared statement.
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Cerevel’s clinical trial success in Parkinson’s follows disappointing results for another company. On Wednesday, Sage Therapeutics reported its Parkinson’s drug candidate dalzanemdor failed to show statistically significant differences compared to a placebo in a Phase 2 clinical trial. This Sage small molecule modulates the NMDA receptor, which plays a role in learning, memory, and cognition. While Sage is discontinuing further development of dalzanemdor in Parkinson’s, the molecule may yet find applications in other neurological diseases. A Phase 2 trial evaluating the drug in Huntington’s disease patients with mild cognitive impairment is on track to yield data in the middle of this year; a separate mid-stage test in Huntington’s patients with cognitive impairment is expected read out in late 2024. Sage expects a Phase 2 test of dalzanemdor in Alzheimer’s disease will have data late this year.
Cerevel focuses on developing drugs for neuroscience indications. The biotech’s pipeline includes emraclidine, a schizophrenia drug candidate in mid-stage clinical testing that could compete with drugs from Bristol Myers Squibb and Neurocrine Sciences. Cerevel has additional clinical-stage programs addressing epilepsy, panic disorder, and dementia-related apathy.
Last December, AbbVie announced an agreement to buy Cerevel, which it said complemented its own neuroscience portfolio. AbbVie markets drugs for migraine, movement disorders, and psychiatric disorders. In Parkinson’s, AbbVie sells Duopa (Duodopa outside the U.S.), a combination of levodopa and carbidopa for treating advanced stages of the disease. The company had also developed ABBV-951 for treating motor fluctuations in adults with advanced Parkinson’s. Last year, the FDA turned down AbbVie’s new drug application for ABBV-951 and asked for more information about the pump that administers the drug. AbbVie said the regulator did not ask for any additional clinical testing.
Cerevel said it continues to expect the acquisition to close in the middle of this year, subject to receipt of regulatory approvals and other customary closing conditions.
Image: Dr_Microbe, Getty Images
