Announcement • Jun 09
Foresee Pharmaceuticals Oral ALDH2 Activator Mirivadelgat Enters Clinical Testing in Parkinson's Disease in the SLEIPNIR Phase 2A Platform Trial
Foresee Pharmaceuticals oral ALDH2 activator, mirivadelgat, has been selected to enter clinical testing in Parkinson's disease in the SLEIPNIR Phase 2a platform trial, in collaboration with Haukeland University Hospital, Bergen, Norway. SLEIPNIR is a multi-arm Phase 2a clinical trial platform designed to evaluate investigational disease-modifying therapies in Parkinson's disease, with focus on brain penetration, biological target engagement, and mechanistic biomarker effects. The trial has been funded by Cure Parkinson's. Mirivadelgat is designed to increase the activity of ALDH2, an enzyme that directly clears these harmful compounds from the brain. By supporting this natural defense system, mirivadelgat accelerates detoxification and could potentially slow the ongoing loss of nerve cells in neurodegenerative diseases, such as PD. The Phase 2a mirivadelgat study in Parkinson's disease is designed to assess whether mirivadelgat reaches the central nervous system, engages its intended biological target, and is safe and well tolerated in people with PD. The study will be conducted as part of SLEIPNIR, a biomarker-driven Phase 2a platform trial designed to accelerate the clinical evaluation of potential disease-modifying therapies for Parkinson's disease. Rather than testing each treatment in a separate stand-alone study, SLEIPNIR evaluates several investigational therapies in parallel using a shared platform design, enabling more efficient assessment of brain penetration, target engagement, and mechanistic biomarker effects. Within the mirivadelgat cohort, 40 eligible participants with Parkinson's disease will be randomized 3:1 to receive either mirivadelgat once daily or matching placebo, in addition to standard dopaminergic treatment. The placebo participants from the mirivadelgat cohort will contribute to a pooled placebo group shared across concurrent SLEIPNIR treatment arms, resulting in an effective comparison of 30 participants receiving mirivadelgat versus 30 participants receiving placebo across the platform. Participants will receive study treatment for 12 weeks, followed by a two-week post-treatment safety follow-up. The primary assessment will take place at the end of the 12-week treatment period, with the week-14 visit used to evaluate safety after treatment discontinuation. Research suggests that toxic compounds called aldehydes can build up inside brain cells, playing a critical role in PD pathogenesis. Over time, aldehydes cause proteins to clump together and contribute to the loss of nerve cells. The PD treatment market will expand over the upcoming years, with overall sales in the US, Japan, and five major European markets growing from $2,200 million in 2023 to $3,600 million in 2032 at a compound annual growth rate (CAGR) of 5.47%. Revenues in the US and European markets are set to increase the most. The market is mainly comprised of levodopa-based therapies, COMT inhibitors, MAO-B inhibitors, and dopamine agonists, many of which are approved for patients with "off" episodes (resulting from long-term use of levodopa), which are more common in late-stage PD patients. Late-stage patients often require more complex and specialized therapies and as a result, developers tend to focus more on this group. Yet, people in the early stages of PD (Stages 1–3) make up about 60% of those receiving treatment, contributing significant revenue to the market. In view of the limited new approved therapies with novel mechanisms, the PD drug market is highly genericized in the US and Europe. While it is expected that several new therapies will enter the market, most focus on improved delivery and reformulation of existing mechanistic classes. Apart from a few new targeted therapies such as alpha-synuclein antibodies currently in development, there remains a high unmet need for first-in-class oral therapies with disease-modifying potential. New treatments with a differentiated clinical profile – including efficacy, safety and convenience - will have an opportunity to unlock a substantial market opportunity.
