Inhibikase Provides Positive Update Regarding Parkinson Agent Risvodetinib

Milton Werner

At the 2024 AD/PD Meeting, held March 5-9, in Lisbon, Portugal, Inhibikase presented an update on its phase 2 study, Trial 201 (NCT05424276), assessing its investigational agent risvodetinib as a potential therapy for Parkinson disease (PD). In total, 25 participants have completed the 12-week treatment period, with patient experience reportedly positive so far.

Risvodetinib is a potent, selective small-molecule medication designed and engineered as chronically administered, once-daily oral medication targeting the underlying biological mechanism resulting in PD< with the goal of halting disease progression and reversing functional loss. The agent is built to block the activation of Abl kinase, a clinically validated drug target, to halt and reverse the loss of dopamine-secreting neurons in the brain and gastrointestinal tract by restoring neuroprotective mechanisms.

Trial 201, a study assessing doses of 50, 100, and 200 mg of once daily risvodetinib, is currently still recruiting. To date, 59 participants have been enrolled, 19 prospective participants are in medical screening, and 54 potential participants are being evaluated for suitability to initiate medical screening. According to Inhibikase, the study is expected to have topline results in the second half of 2024, depending on the date of last recruitment.

"Parkinson’s disease remains one of the most prevalent neurodegenerative diseases worldwide, affecting more than a million people in the U.S. alone. The 201 Trial evaluating three doses of risvodetinib in untreated Parkinson’s patients is beginning to yield information about the experience of participants on risvodetinib," Milton Werner, president and chief executive officer at Inhibikase, said in a statement.¹ "While the trial is ongoing, we remain blinded to which participants are administered risvodetinib. Fourteen percent of participants have reported a side effect that might be related to study drug and none of the reported side effects have been clinically meaningful."

He added, "Moreover, participants’ experience in the trial appears to be positive. Twenty-five people have completed the 12-week dosing course and all have indicated interest to continue into the 12 month extension study when available."

Although the motor and non-motor functional assessments could not be interpreted from blinded results, the company noted that clinician and patient impression of disease status or severity did not change over the 12-week period. Among the 12 patients who’ve completed the 12-week dosing period, 10 mild and 1 moderate AEs potentially related to risvodetinib were reported.

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In addition to safety, the study also assesses several secondary outcomes including Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Parts II and III, Patient and Clinician Global Impression Severity, Non-Motor Symptom Scale, and Epworth Sleepiness Scale, among others. Furthermore, the trial also evaluated change in phosphorylated ⍺-synuclein in cerebrospinal fluid and phosphorylated ⍺-synuclein in skin.

To assess the safety, tolerability, and pharmacokinetics of risvodetinib, investigators previously conducted a phase 1 study of healthy volunteers that featured a single-ascending dose (SAD) and 7-day multiple ascending dose (MAD) portion. In the trial, participants were randomized 3:1 across 9 SAD doses and 3 MAD doses of the agent or placebo. Following that, part 3 of the study was also a MAD, conducted at 2 doses in 14 participants with mild-to-moderate PD.

All told, risvodetinib was well tolerated, had a favorable safety and pharmacology profile over 7-day dosing, and did not induce serious AEs. Single dose pharmacokinetics were approximately linear between 12.5 mg and 200 mg for both C_max and AUC_{0 - inf} without distinction between healthy volunteers and participants with PD. Treatment with risvodetinib did not result in AEs in participants on stable regimen of PD medications, suggesting that the agent could be compatible with other treatments in this patient population. This was true among participants who remained on their anti-PD medications as well as those who remained on other medications administered for comorbid indications.

REFERENCES
1. Inhibikase Therapeutics to provide trial update for risvodetinib at the 2024 International Conference on Alzheimer’s and Parkinson’s Diseases and Related Neurological Disorders. Inhibikase Therapeutics. March 7, 2024. Accessed March 19, 2024. https://www.inhibikase.com/news/press-releases/detail/112/inhibikase-therapeutics-to-provide-trial-update-for
2. Milton W, Warren OC, McGarry A, et al. A phase 1, randomized, SAD, MAD, and PK study of risvodetinib in older adults and Parkinson’s disease. Journ of Parkinsons. 2024;14(2):325-334. doi:10.3233/JPD-230319