Phase 3 program for Parkinson’s drug risvodetinib gets FDA review
Goal was to define outcome measures, see if more needed for application
Risvodetinib, an experimental oral small molecule Abli Therapeutics is developing for people with untreated Parkinson’s disease, may be one step closer to Phase 3 clinical testing, following a meeting with U.S. regulators.
The end-of-Phase 2 meeting’s main goal with the U.S. Food and Drug Administration (FDA) was to define the outcome measures for a Phase 3 study and to see if any more information is needed to file a new drug application, according to a company press release.
The company, which spun off from Inhibikase Therapeutics to focus on treatments for neurodegenerative diseases that arise from the activation of Abelson tyrosine (c-Abl) kinases, has reviewed the design of its planned Phase 3 program that’s building on outcomes of the 201 Phase 2 study (NCT05424276).
What is risvodetinib designed to do in Parkinson’s?
Risvodetinib, formerly IkT-148009, is designed to block c-Abl kinases, a type of enzyme involved in several processes within cells. It’s believed that c-Abl kinases are overactive in Parkinson’s, contributing to the disease.
By blocking c-Abl kinases, risvodetinib is expected to protect nerve cells in the brain, called dopaminergic neurons, that produce dopamine, a chemical important for motor control. This could help prevent the loss of these nerve cells and may slow or stop Parkinson’s progression.
In the fully enrolled 201 study, patients with bradykinesia, or slowness of movement, a hallmark symptom of Parkinson’s, were randomly assigned to receive risvodetinib as a capsule once daily at 50, 100, or 200 mg, or a placebo for 12 weeks.
Treatment with risvodetinib led to improvements on both the MDS Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and the Schwab and the England Activities of Daily Living scale, clinical tools that measure how severe symptoms are and how the disease limits functional independence.
The FDA expressed support for using MDS-UPDRS Part 2, which evaluates activities of daily living, as the primary endpoint for the Phase 3 study. This outcome is seen as clinically meaningful and directly relevant to a patient’s quality of life.
A new secondary endpoint was also proposed: measuring the time to start levodopa/carbidopa — a mainstay Parkinson’s treatment. Since starting it typically marks disease progression, delaying it could be considered evidence of disease modification. However, clinical criteria for when to start levodopa/carbidopa must still be defined.
The FDA also agreed to reduce the frequency of vision assessments in the Phase 2 trial. Eye checks will now be every six months, until the FDA reviews a year of dosing data. So far, no vision issues related to risvodetinib have been seen. The agency also encouraged continued investigation into biomarkers in skin and bodily fluids to monitor treatment response.
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