High-dose risvodetinib effective, safe for Parkinson’s, new data show
Unblinded data from 201 trial show benefits with therapy, formerly IkT-148009
A once-daily 200 mg dose of Inhibikase Therapeutics’ risvodetinib — an oral medication previously called IkT-148009, now undergoing Phase 2 clinical testing — is safe, and can improve motor function and ease activities of daily living in people with previously untreated Parkinson’s disease.
That’s according to now unblinded data from 11 patients who had been enrolled in the company’s 201 trial prior to a temporary two-month clinical hold placed on the study last year. That hold, by the U.S. Food and Drug Administration (FDA), was due to safety concerns regarding the medication’s higher dose. However, it was lifted in January and enrollment in the trial has since resumed.
Risvodetinib also was found to reach steady levels in the body after up to five days without causing any serious side effects at any of the three doses tested.
These data were shared in an oral presentation, titled “Analysis of the therapeutic potential of IkT-148009 in Parkinson’s disease,” at this year’s Movement Disorders Society (MDS) congress, recently held in Copenhagen, Denmark.
“While the dataset presented during the MDS congress has too few participants to conclude clinical benefit, we find these data to be cautiously encouraging as we continue to enroll patients into the ongoing 201 trial,” Milton Werner, PhD, Inhibikase’s president and CEO, said in a company press release.
Risvodetinib trial had been put on a clinical hold, now lifted, by the FDA
Running at multiple sites across the U.S., the 201 trial (NCT05424276) is recruiting up to 120 adults with Parkinson’s, ages 30 to 75, who have received no prior treatment and are currently not taking any medications to control their disease. Those interested in participating can check their eligibility on the trial’s portal.
“To date, 171 people have been pre-qualified through the portal. These individuals are now in the process of engaging with one or more of our active clinical sites to learn more about the trial and/or set-up evaluation appointments,” Werner said.
Risvodetinib is a small molecule that’s designed to block Abelson tyrosine kinase (c-Abl), a protein that helps neurons, or nerve cells, respond to damage. Blocking c-Abl is expected to reverse the loss of dopamine-producing neurons, a hallmark of Parkinson’s, thereby slowing or halting disease progression.
The 201 trial is testing how safe and well tolerated risvodetinib is versus a placebo when given once a day as a gelatin capsule at a dose of 50, 100, or 200 mg for 12 weeks, or about three months. It’s also testing how well risvodetinib works in easing symptoms of Parkinson’s, both motor and nonmotor.
The 11 patients withdrew from the trial following the FDA’s clinical hold. Among them, eight had been randomly assigned to take risvodetinib — three at 50 mg, two at 100 mg, and three at 200 mg — and three were given a placebo.
Motor and nonmotor function were assessed using the MDS Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) parts II and III combined. A higher score means worse symptoms, and clinical improvement was defined as a reduction of 3-4 points from the trial’s start to week 12.
Patients given the 200 mg dose had a combined score that was lower by an average of 8.7 points. For those on the 100 mg dose, the score dropped by 1.3 points. By contrast, patients given the 50 mg dose or a placebo saw an average increase of 1.7 points.
These outcomes warrant the continued evaluation of [risvodetinib] as a potential disease-modifying therapy for [Parkinson’s].
The Schwab & England (S&E) Activities of Daily Life Scale, in which a higher score reflects worse outcomes, was used as an additional measure of daily function.
From the study’s start to week 12, patients given the 200 mg dose experienced a 3.3-point reduction in the S&E scale, while those given a placebo had an increase of 3.3 points. That made for a 6.6-point spread between the two groups. The score dropped by an average of five points in the 100 mg group.
A total of seven side effects possibly related to treatment were reported, but none was of clinical significance. There were no serious side effects.
“[Risvodetinib] was shown to be relatively safe and induced no serious or clinically significant adverse events across a wide dosing range,” the researchers wrote.
According to the team, “these outcomes warrant the continued evaluation of [risvodetinib] as a potential disease-modifying therapy for [Parkinson’s].”