Levodopa, widely considered the standard of care for Parkinson’s disease, can reduce symptoms such as slow movement, stiffness, and tremors. But many patients taking the drug still experience “OFF time,” or periods where Parkinson’s symptoms present despite medication.
Cerevance is targeting these fluctuations with a planned Phase II/III trial of its investigational compound CVN424, CMO Jordan Dubow says. The Boston-based biotech plans to initiate the study in the first quarter of 2023, testing CVN424 as an adjunctive therapy to levodopa, he adds.
As a primary endpoint, the planned Phase II/III will target a reduction in OFF time, Dubow says. Patients measure OFF time in diaries, where they record their symptoms every 30 minutes for a two-day period before and after treatment to determine OFF time decrease.
Parkinson’s disease is a progressive central nervous system disease associated with deficiencies in the neurotransmitter dopamine. Levodopa can be converted into dopamine, and CVN424 can modulate targets associated with dopamine receptors.
Cerevance Parkinson’s disease trial plan details
The planned Phase II/III will likely recruit around 110 patients in each of three treatment arms: low-dose CVN424, high-dose CVN424, and placebo, Dubow says. Cerevance will likely power the trial to show a 1.3-hour reduction in OFF time, accounting for a drop-out rate of around 15%, he adds.
Although Dubow did not state the planned length of the Phase II/III, he says the FDA typically requires studies of at least 12 weeks to get an approval.
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In a previous, 135-patient Phase II trial, the high dose of CVN424 showed a 1.3-hour reduction in OFF time after four weeks (p=0.042), according to a March 31 press release. CVN424 was well-tolerated, with most common adverse events being nausea, vomiting, and headache in two subjects each.
While the Phase II trial enrolled patients with Parkinson’s disease with at least two hours of average OFF time at baseline, the Phase II/III will enroll patients with at least three hours of OFF time, Dubow says. Historically, it has been difficult to show reductions in OFF time for patients with a baseline of less than three hours, he explains.
The journey to approval in Parkinson’s
To gain regulatory approval in Parkinson’s disease, the FDA requires two late-stage trials, Dubow notes. The planned Phase II/III trial of CVN424 as an adjunctive therapy to levodopa will serve as the first registrational study, he adds.
Cerevance plans to run a second, large registrational study testing CVN424 as a monotherapy for patients who are not on levodopa, Dubow says. The biotech will first run a smaller proof-of-concept study in this population, though there is not a finalised timeline, he adds.
As for financing, Cerevance intends to raise $80–100 million beginning at the end of this year or start of next year, says CEO Craig Thompson. Previously, Cerevance raised $65 million in a Series B fundraise, a July 2020 press release states.
Trends in Parkinson’s drug development
In 2021, pharmaceutical companies initiated 88 Phase I–III clinical trials in Parkinson’s disease, the highest number on record, according to GlobalData’s Clinical Trial Database. The number of clinical trial initiations in Parkinson’s disease steadily rose between 2015 and 2018 before dips in 2019 and 2020. GlobalData, the parent company of Clinical Trials Arena, found that the proportion of Parkinson’s disease trial initiations fell from 2019 because of Covid-19.
Elsewhere in Parkinson’s disease, Annovis Bio CEO Maria Maccecchini also discussed the company's Phase III trial plans and recruitment strategies with Clinical Trials Arena. Meanwhile, experts remain hopeful Roche’s prasinezumab can overcome a series of failures in Parkinson’s disease. Finally, researchers and pharmaceutical companies are working to develop vaccines that could protect against the neurodegenerative disease.