Cerevance's oral non-dopaminergic therapy has redeemed itself by improving both motor and non-motor symptoms in a phase 3 Parkinson's disease study. The win came over a year after the non-dopaminergic therapy missed its primary endpoint in a phase 2 monotherapy study.
The GPR6 inverse agonist, called solengepras, significantly reduced OFF time, a term for the period when medication wears off and symptoms return or worsen between doses. Based on the findings, the Boston biotech plans to seek FDA approval of solengepras for Parkinson’s disease, according to an Oct 7. release.
The phase 3 trial enrolled 341 participants to receive either 150 mg or 75 mg doses of solengepras, or placebo, orally once daily for 12 weeks as an adjunctive treatment to levodopa in Parkinson’s patients experiencing motor fluctuations.
Patients treated with 150 mg solengepras showed a reduction in average daily OFF time of 0.61 hours versus placebo at Week 12, with improvements seen as early as Week 2. The 150 mg dose also increased ON time—the period when the medication is working effectively and movement symptoms are well-controlled—by 0.60 hours compared to placebo.
In addition, Cerevance reported daily living and non-motor improvements in patients who received 150 mg solengepras, with a 1.91-point increase on a Parkinson’s rating scale and a 0.98-point improvement in daytime sleepiness when compared to placebo.
“Daily function, alertness and quality of life are measures that reflect how people with Parkinson's experience their day,” Cerevance CEO Craig Thompson said in the release.
“As a potential first-in-class, non-dopaminergic therapy, solengepras gives us the opportunity to evaluate what a new mechanism may offer people with Parkinson’s,” said Thompson, who added that the company plans to discuss the results with the FDA “to determine next steps.”
Parkinson’s occurs due to progressive death of dopamine-producing neurons in a region of the brain called the substantia nigra, which is a part of the basal ganglia. One role of dopamine in the brain is to communicate to the body to make smooth, coordinated muscle movements—hence the disruption in movement seen in Parkinson’s disease when this chemical messenger is lost.
Levodopa is the FDA-approved gold-standard treatment for the disease. The treatment is a precursor to dopamine that can cross into the brain and replace the missing dopamine.
Cerevance is taking a non-dopaminergic approach. Solengepras selectively targets the indirect basal ganglia pathway by inhibiting GPR6 receptors, which are enriched in dopamine-expressing neurons. In Parkinson’s, the loss of dopamine leads to hyperactivity of the indirect basal ganglia pathway, acting like a brake on movement. Solengepras’ mechanism is designed to release the brake and restore normal movement.
Today's phase 3 success follows a mid-stage failure of solengepras as a monotherapy in untreated patients in April 2025, where solengepras was statistically no better than placebo on a Parkinson's disease scale by 12 weeks. At the time, the biotech blamed the miss on results for a physician-administered neurological exam, which assesses physical signs of Parkinson’s at a single point in time, while also pointing to “trends in improvement” on two patient-reported parts of the endpoint.
Parkinson’s has proved a vibrant area of research and deal-making in recent weeks. On Monday, Roche's Genentech paid Alector $100 million for its enzyme replacement therapy, while last month saw AbbVie secure FDA approval for its $8.7 billion bet on Cerevel Therapeutics’ tavapadon in adults with Parkinson’s. Meanwhile, San Diego-based Aspen Neuroscience is planning for a phase 3 study push for autologous stem cells aimed at restoring neurons in the brain, while BioVie has struggled to persuade investors of the promise of its phase 2 asset bezisterim.