Risvodetinib

Inhibikase Therapeutics is slamming the brakes on its Parkinson’s disease program after the candidate failed to improve symptoms in a mid-stage test in treatment-naïve patients. The biotech’s risvodetinib didn’t meet the Phase 2 trial’s key secondary endpoint of improvement in the sum of parts 2 and 3 of the Movement Disorder Society-Universal Parkinson’s Disease Rating Scale (MDS-UPDRS) at any dose level, according to an SEC filing posted Wednesday. The placebo-controlled study enrolled 126 people with untreated disease. The trial did hit its safety-related primary endpoint, with 95% of subjects completing 12 weeks of treatment with risvodetinib. The 100 mg dose also produced a 1.41-point reduction in part 2 of the MDS-UPDRS, for an unadjusted p-value of 0.036. Inhibikase said it plans to present full data from the Phase 2 trial of the c-Abl tyrosine kinase inhibitor at a future medical meeting. The biotech’s share price $IKT slid around 15% postmarket Wednesday, but has since rallied. Nonetheless, Inhibikase is pausing further development of risvodetinib and considering “strategic options” for the program. It will instead focus on advancing its lead pipeline candidate for pulmonary arterial hypertension (PAH). The candidate — another c-Abl tyrosine kinase inhibitor called IkT-001Pro — is in Phase 3 for stable-phase chronic myeloid leukemia and preclinical development for PAH. This is not the first time risvodetinib has faced setbacks. In 2022, the FDA placed a full clinical hold on the drug, which at the time was being developed for both Parkinson’s and multiple system atrophy. The hold was lifted less than three months later after the company agreed to implement the agency’s requests for more detailed ocular monitoring.

iStock, Afry Harvy Inhibikase’s setback continues biopharma’s losing streak against Parkinson’s, marked by several clinical failures and abandoned assets in recent months. Inhibikase Therapeutics on Wednesday announced that it will suspend the further development of its investigational drug risvodetinib in Parkinson’s disease. The decision was spurred by underwhelming findings from a Phase II trial, which the biotech in an SEC filing said met its primary efficacy endpoint of safety and tolerability but failed to demonstrate significant efficacy. Inhibikase provided limited data in its regulatory document, but promised to present a more complete readout and analysis at a future medical congress. In a hierarchy of 15 functional endpoints, risvodetinib failed to elicit a significant improvement in the top measure, which was the sum of scores in parts 2 and 3 of the Movement Disorder Society Universal Parkinson’s Disease Rating Scale (MDS-UPDRS). Still, Ironwood flagged certain promising signals of efficacy. Patients treated with 100 mg risvodetinib saw a 1.41-point improvement in part 2 of the MDS-UPDRS, an effect with a nominal p-value of 0.036, according to the biotech. Meanwhile, the 50-mg dose led to a 4% increase in the results of the Schwab & England Activities of Daily Life Scale, a treatment effect with a nominal p-value of 0.0004. With risvodetinib paused, Inhibikase is switching its focus to its new lead program IkT-001Pro, which it is developing for pulmonary arterial hypertension. The biotech will look at potential strategic options for risvodetinib but has yet to specify possibilities such as licensing deals or a sale. Aside from Parkinson’s, Inhibikase was also trialing risvodetinib for neurogenic constipation, dysphagia and multiple system atrophy. Inhibikase’s stock price declined more than 19% in after-hours trading at $2.26 per share, down from $2.80 at the previous close. Risvodetinib’s discontinuation highlights the difficulties of developing effective therapies for Parkinson’s disease, a therapeutic space that has suffered several stumbles and even more abandoned assets in recent months. Last month, for instance, Roche disclosed that its Prothena-allied prasinezumab failed a Phase IIb Parkinson’s study, unable to significantly slow motor progression in patients. Just days earlier, Novartis and UCB announced that their drug candidate minzasolmin likewise failed a proof-of-concept Parkinson’s study. Fellow Big Pharma Johnson & Johnson has also struggled with Parkinson’s, revealing in October 2024 that it would no longer invest in JNJ-0376, an early-stage drug candidate that, according to an earlier business presentation , had “novel mechanisms to modify, treat and/or prevent neurodegenerative disorders.” In April of the same year, Sage Therapeutics was also forced to turn its back on its Parkinson’s program for the oral asset dalzanemdor after a mid-stage study found no significant cognitive improvements in treated adult patients.