IRLAB announces top-line results from Phase IIb trial of mesdopetam (IRL790) in Parkinson’s disease

The Phase IIb trial objective was to investigate efficacy and safety of three doses of mesdopetam (2.5, 5.0, and 7.5 mg bid), as compared to placebo, in people with Parkinson’s disease experiencing troublesome dyskinesia caused by their levodopa treatment and to support dose selection for further clinical development. The primary endpoint, change in daily ON-time without troublesome dyskinesia (“good ON”-time), did not reach statistical significance by mesdopetam compared to placebo. A secondary efficacy endpoint, UDysRS (part 1, 3 and 4, full analysis set), a comprehensive scale measuring ON-phase dyskinesia, showed significant anti-dyskinetic effects by mesdopetam already at four weeks (nominal p-value = 0.045), at eight weeks (nominal p-value = 0.004), continuing for the full twelve-week study period (nominal p-value = 0.026) at the 7.5 mg bid dose. This effect was corroborated by the numerical improvement in scales measuring disability associated with dyskinesia. Further, the daily time spent in OFF showed a dose-dependent pattern and a numerical decrease compared to placebo also favoring the 7.5 mg bid dose. The secondary endpoint MDS-UPDRS part II (motor aspects of experiences of daily living) was unchanged by mesdopetam treatment, which was the desired outcome as it shows that mesdopetam does not impair normal motor function in this study population.
 
“Although the study did not meet its primary efficacy endpoint, a well-established scale used to assess dyskinesia, the UDysRS, demonstrated anti-dyskinetic effects by mesdopetam. Notably, these anti-dyskinetic properties were obtained without impairing normal motor function and are further strengthened by an apparent reduction in OFF-time. The effect is observed at doses with a side effect profile on par with placebo. This was also a dose-finding study and we now have a clear understanding that 7.5 mg bid is the preferred dose for further clinical studies. We will now together with our partner Ipsen continue analyses of the study data and prepare to present further results at scientific conferences during 2023,” said Nicholas Waters, EVP and Head of R&D, IRLAB.

The findings from the Phase IIb trial showed that mesdopetam was well tolerated and displayed an acceptable safety profile. The adverse event profile of mesdopetam in the Phase IIb study was similar to placebo. Early withdrawal from the study due to any adverse events occurred in similar proportions in the mesdopetam treatment arms and the placebo arm, indicating good tolerability. Any reported adverse events were 56.9% in mesdopetam-treated subjects compared to 46.2% in placebo. The most common adverse events reported by system organ class (SOC) were nervous system disorders reported by 19.8% of mesdopetam-treated subjects and 23% of placebo-treated subjects. Parkinsonism was reported by 4.3% of mesdopetam-treated subjects and 10.3% of placebo-treated subjects. A small number of subjects treated with mesdopetam (6.9%), compared to 0% placebo, reported decreased mobility during the first month of treatment which was not seen during the second and third months of treatment. There were seven randomized patients reporting Serious Adverse Events (SAEs) of which four were in the mesdopetam treatment arms and three in placebo. One SAE was considered probably related to mesdopetam treatment. There were two deaths not considered related to mesdopetam. In the study, 195 patients were screened, 156 patients were randomized, and 125 patients completed the twelve-week treatment period.

“Unfortunately, the primary endpoint to increase “good ON”-time compared to placebo was not met. I am, however, encouraged that the UDysRS results suggest that mesdopetam has potential to become an effective treatment of Parkinson’s disease. Clearly, further detailed analysis is required to fully understand the potential of this first-in-class compound. I am grateful to the clinical development team, PIs and CRO for their diligent and hard work with the Phase IIb trial, and I would like to thank the patients and their caregivers for their trust and participation in this study,” said Richard Godfrey, Chief Executive Officer, IRLAB.

Further analysis of the full data will be carried out and full disclosure of the detailed results from the Phase IIb trial will be made in abstracts at future scientific congresses and publications in scientific journals.

The global specialty pharma company Ipsen holds the exclusive right for further clinical development and commercialization of the mesdopetam program in PD-LIDs and potentially other indications.