IRLAB provides update on mesdopetam’s Phase IIb study data and the plans toward Phase III

In-depth analyses of the Phase IIb study data have now been completed confirming the great potential of mesdopetam in people living with PD-LIDs. The objectives of the study were to investigate the efficacy and safety of three doses of mesdopetam (2.5, 5, and 7.5 mg twice daily (b.i.d.)), as compared to placebo, in people living with PD-LIDs to guide dose selection for Phase III. Top-line results from the Phase IIb study of mesdopetam in PD-LIDs were communicated in January 2023.
 
In the in-depth evaluation of the Phase IIb study data the effects in subjects based both on their randomized dose (FAS population) and based on the actual dose received in subjects compliant with the protocol (PS population), were analyzed. Since dose adjustment was allowed at one time during this study, analyses based on the actual dose received are important to get a full understanding of the dose dependency and the treatment effects. These analyses provide the basis for dose selection for Phase III.

“We are pleased to see clear and clinically meaningful anti-dyskinetic effects of mesdopetam in the analyses of the Phase IIb study data. Consistent dose-response patterns were observed across the key efficacy endpoints assessing dyskinesia: “good ON”-time, UDysRS, UDysRS subscales. This, in combination with unchanged MDS-UPDRS part 2 scores demonstrates that mesdopetam shows anti-dyskinetic efficacy without affecting normal motor function, or negatively impacting the anti-parkinsonian treatment effect of levodopa. The reduced OFF-time even indicates that mesdopetam has anti-parkinsonian effects,” said Nicholas Waters, EVP and Head of R&D, IRLAB. “The dose-dependent effects make it possible to select dose for Phase III.”

In the FAS, mesdopetam’s treatment effect on Hauser diary “good ON” (ON-time without troublesome dyskinesia) did not reach statistical significance, whereas in the PS, among subjects taking the 7.5 mg b.i.d. dose of mesdopetam, a significant and clinically meaningful increase in “good ON”-time of 1.75 hours vs placebo (“good ON” scaled to 16 hours awake time, p=0.050) was observed.

In the FAS, mesdopetam demonstrated significant anti-dyskinetic effects, as measured by UDysRS, sum of parts 1, 3 and 4, with a reduction of 6.2 points vs. placebo (p=0.026) at 7.5 mg b.i.d. In the PS, the effect on UDysRS was dose-dependent and a reduction of 9.2 points vs. placebo (p=0.011) was observed at 7.5 mg b.i.d. In the UDysRS disability score parts 1b+4, assessing the degree of disability caused by dyskinesia, there was a reduction of 3.5 points vs. placebo (p=0.062) in the FAS and, in the PS a reduction of 5.5 points vs placebo (p=0.019) was observed at 7.5 mg b.i.d.

This means that both patients and physicians report reduced disability related to dyskinesia during mesdopetam treatment. Further, the daily time spent in OFF showed a clear dose-dependent pattern and a decrease compared to placebo in both FAS and PS, reaching 1.27 hours (p=0.051) at the 7.5 mg b.i.d. dose in the PS, indicating a direct anti-parkinsonian effect of mesdopetam in subjects treated with levodopa. Mesdopetam was well tolerated with an adverse event and safety profile on par with placebo.

“I think the mesdopetam data package is one of the most compelling available in the symptomatic treatment of Parkinson’s. Mesdopetam has the rare ability to both improve dyskinesias and improve parkinsonism and, at the same time, appears to be well tolerated. I expect it will have both clinical utility and commercial success,” said Karl Kieburtz, MD, MPH, Professor in Neurology, Former chairman of the Peripheral and Central Nervous System US FDA Advisory Committee; chairman of the Scientific Evaluation Committee for the Cooperative Studies Program, Veterans Administration, and the National Institute of Neurologic Disorders and Stroke.
 
The Phase I clinical studies performed by Ipsen to prepare for Phase III were successfully completed and showed favorable results. One study evaluated pharmacokinetics (PK) in different populations showing that mesdopetam has similar PK in Asian and Non-Asian populations. A second study evaluated the potential for PK drug-drug interactions, via key drug metabolizing enzymes, showing a low risk of drug-drug interaction, suggesting that neither additional clinical drug-drug interaction studies nor restrictions on future patient enrolment would be required in future clinical studies. A third study investigated elimination routes of mesdopetam showing no risk of accumulation of mesdopetam in the body. Safety data from all three studies did not reveal any new safety signals and thus, was consistent with the current knowledge of the safety profile for mesdopetam.
 
“The data from the three Phase I studies performed by Ipsen are encouraging as they suggest that treatment with mesdopetam will be predictable and with little variability. This will most likely result in a simple uniform dosing of the drug, which minimizes the risk of dosing errors and is an advantage for mesdopetam over current alternatives in the management of dyskinesia in Parkinson’s,” commented Joakim Tedroff, CMO, IRLAB.
 
“I am excited by the potential of mesdopetam both commercially and how it truly can benefit people living with Parkinson’s. The aging global population driving the increased prevalence of Parkinson’s and people developing levodopa-induced dyskinesia suggest that mesdopetam could play an important role in this large and growing unmet clinical need. I will focus on leading the continued work toward Phase III together with our regulatory, clinical, and financial advisors. We anticipate that this strengthening of our portfolio with the Phase III ready mesdopetam project will improve our partnering and financing opportunities to advance our world-leading portfolio of treatments in Parkinson’s disease,” said Gunnar Olsson, CEO, IRLAB.
 
In conclusion, available data indicate that mesdopetam has dose-dependent anti-dyskinetic and anti-parkinsonian effects combined with a tolerability and safety profile not different from placebo, giving mesdopetam a unique position in the competitive landscape. The comprehensive data package developed by IRLAB and Ipsen provides a solid foundation for continuing the development of mesdopetam to Phase III. IRLAB now proceeds with preparations for Phase III, requesting an end-of-Phase 2 meeting with the US FDA to define the Phase III study program.
 
Comprehensive results of the Phase IIb study of mesdopetam in PD-LIDs will be presented at MDS Congress in Copenhagen held on August 27-31, 2023. As IRLAB secured full ownership of the mesdopetam project, all further communications concerning mesdopetam are now the responsibility of IRLAB.