Risvodetinib: A Promising Breakthrough in Parkinson’s Disease Treatment

• Inhibikase Therapeutics’ lead product candidate, Risvodetinib (IkT-148009), represents a novel therapeutic approach in the treatment of Parkinson’s disease. Unlike traditional treatments that focus on managing symptoms, Risvodetinib targets the underlying biological mechanisms driving disease progression.
• Risvodetinib’s mechanism of action offers the potential for disease modification in Parkinson’s disease patients. By restoring neuroprotective mechanisms through Abl kinase inhibition, Risvodetinib seeks to not only halt disease progression but also reverse functional loss associated with the condition.

The ongoing 201 Trial evaluates the safety, tolerability, and clinical benefit of risvodetinib in untreated Parkinson’s Disease patients. With participants randomized across therapeutic doses and placebo groups, safety measures include evaluation of treatment-emergent adverse events, cardiovascular safety, standard laboratory analyses, and monitoring for changes in vision. Early indications suggest promising safety and tolerability profiles, laying a solid foundation for further investigating risvodetinib’s therapeutic efficacy. 

Risvodetinib’s mechanism of action, targeting alpha-synuclein aggregate pathology, holds the potential for significant clinical benefit in Parkinson’s Disease. The trial’s secondary endpoints, including measures of motor and non-motor function in the Central and Enteric Nervous Systems, offer comprehensive insights into Risvodetinib’s therapeutic effects. Biomarker analysis using CSF/plasma assessment and skin biopsy further complement functional assessments, providing a multifaceted approach to evaluating treatment efficacy.

Since the trial started, Inhibikase Therapeutics has been making significant strides in developing risvodetinib (formerly IkT-148009), an innovative oral therapy aimed at altering the course of Parkinson’s disease treatment. This promising drug, now undergoing Phase II clinical evaluation, seeks to slow or even halt the progression of this debilitating neurodegenerative condition. Here’s a closer look at its development milestones and the encouraging results emerging from the ongoing 201 trial.

Patient Enrollment Complete for Phase II Trial

As of June 2024, Inhibikase announced the completion of patient enrollment in its 201 trial (NCT05424276). The study involves 120 participants across 32 sites in the U.S., with an expected total enrollment of 126 to accommodate pre-screened individuals. This trial aims to assess the safety and efficacy of risvodetinib in untreated Parkinson’s patients.

To date, 69 participants have completed dosing, with 32 mild and five moderate adverse events potentially linked to the treatment. Despite these, early data from 25 patients indicated that risvodetinib successfully stabilized disease progression and symptom severity, offering hope to the Parkinson’s community. The company plans to share top-line results in the fourth quarter of 2024, with Phase III discussions with the FDA anticipated by year-end.

A Novel Tablet Formulation

In August 2024, Inhibikase introduced a breakthrough in drug delivery with a newly designed tablet formulation of risvodetinib. This formulation enhances drug exposure, nearly doubling steady-state levels compared to the current capsule form used in the trial. This innovation has the potential to lower required doses, improving both safety and tolerability.

Moreover, the smaller tablet size addresses the swallowing difficulties often faced by Parkinson’s patients, ensuring greater patient comfort and compliance. This novel formulation is expected to be rolled out in a planned 12-month extension of the ongoing trial, further advancing the treatment’s potential.

Encouraging Phase II Data Presented at MDS Congress

In October 2024, new unblinded data from the 201 trial showcased risvodetinib’s promise. A once-daily 200 mg dose demonstrated safety and efficacy in improving motor function and easing daily activities for untreated Parkinson’s patients. These findings stemmed from 11 participants who continued in the trial following a temporary FDA-mandated clinical hold in 2023, which was lifted in January 2024.

Risvodetinib was shown to reach steady levels in the body within five days without serious side effects, regardless of the dose tested (50, 100, or 200 mg). While the dataset remains small, these preliminary results were described as “cautiously encouraging” by Dr. Milton Werner, President and CEO of Inhibikase, during his presentation at the Movement Disorders Society (MDS) congress in Copenhagen.

Looking Ahead

The progress of risvodetinib in Phase II trials underscores Inhibikase’s commitment to developing transformative therapies for Parkinson’s disease. With patient enrollment complete, a novel formulation ready for implementation, and preliminary data showing promising outcomes, risvodetinib could become a game-changer in Parkinson’s treatment.

The company now analyzes top-line data and plans pivotal Phase III trials. As we await further results, risvodetinib remains a beacon of hope for those living with Parkinson’s, representing a step closer to modifying the course of this challenging disease.