AAN 2025 | Phase II and III trials of solengepras for the treatment of ‘off’ episodes in Parkinson’s disease
Stuart Isaacson, MD, Director of the Parkinson’s Disease and Movement Disorders Center of Boca Raton, Boca Raton, FL, discusses a novel mechanism involving the inhibition of GPR6 to treat ‘off’ episodes in patients with Parkinson’s disease. The GPR6 inhibitor solengepras has shown promise in a Phase II proof-of-concept study, and a Phase III trial is currently underway to further evaluate the efficacy and safety of this agent in treating these fluctuations. This interview took place at the 77th American Academy of Neurology (AAN) Annual Meeting in San Diego, CA.
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Transcript
Many of our patients who are treated with levodopa have a robust response, but within a few years, invariably, they develop these off-fluctuations. Fluctuations in how quickly a dose of levodopa may begin to give benefit and the duration of benefit from each individual dose. We’ve had a number of strategies of trying to increase the dose of levodopa, the frequency of dosing, using extended-release formulations, but we’re still left with many patients who continue to experience these off fluctuations during which they have both motor and often non-motor symptoms...
Many of our patients who are treated with levodopa have a robust response, but within a few years, invariably, they develop these off-fluctuations. Fluctuations in how quickly a dose of levodopa may begin to give benefit and the duration of benefit from each individual dose. We’ve had a number of strategies of trying to increase the dose of levodopa, the frequency of dosing, using extended-release formulations, but we’re still left with many patients who continue to experience these off fluctuations during which they have both motor and often non-motor symptoms. So it’s been a big unmet need for our patients. So looking at a novel mechanism by inhibiting GPR6 on the indirect pathway and really taking that brake off, in a Phase II proof of concept study, solengepras was able to improve, reduce the off time, seemed to also increase the good on time. And interestingly, it did this to a greater extent in people who had greater problems with off fluctuations and people who had three or more hours, we saw even greater benefit. This was really interesting because it gives us a novel mechanism trying to help people that’s non-dopaminergic and seems to be tolerated without some of the non-motor worsening of symptoms as well as other dopaminergic symptoms that have limited other dopaminergic therapies. And we’re now looking at a large Phase III trial that’s ongoing and enrolling now to really try to demonstrate the efficacy, safety, and tolerability of solengepras trying to treat these fluctuations. So we await those results eagerly.
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