Study demonstrates leriglitazone improves relevant disease biomarkers and ataxia resulting in clinical benefit in this orphan disease


Mataró, Barcelona, Spain, December 15, 2020 - Minoryx Therapeutics, a Phase 3 clinical stage biotech company focused on the development of differentiating treatment options in orphan central nervous system (CNS) disorders, today announces topline results from the Phase 2 FRAMES clinical trial. The study evaluates leriglitazone, a novel, selective PPARγ agonist, in patients with Friedreich's ataxia (FRDA). FRDA is a life-threatening disease characterized by neurodegeneration and results in a loss of coordination, muscle strength and cardiomyopathy.

The Phase 2 clinical trial was a proof of concept, multicenter, double-blind and placebo-controlled study. 39 patients were enrolled, with 32 completing the study. Treatment with leriglitazone resulted in PPAR engagement, within the target range, in all patients as assessed by the relevant biomarker (adiponectin). Results of the trial show modulation of the Frataxin pathway and restoration of the bioenergetics deficits by leriglitazone in Friedreich's ataxia patients. These signals are consistent with the mechanism of action of leriglitazone, recently published by the journal Neurobiology of Disease (Rodríguez-Pascau et al. 2021).

“Minoryx’s lead clinical candidate, the PPAR agonist leriglitazone, can target multiple CNS diseases. Friedreich's ataxia is a potentially fatal neurodegenerative condition that has severe and worsening symptoms for sufferers. Developing therapeutic options for this condition is vital for patients,” said Marc Martinell, CEO, Minoryx. “We believe that the Phase 2 FRAMES trial data shows promising proof of concept as a therapy for Friedreich's ataxia, despite the inconclusive results of the primary endpoint, and provide a clear demonstration of the mechanism of action of leriglitazone. We intend to initiate discussions with regulatory agencies to define the clinical development path forward to deliver this therapy to Friedreich's ataxia patients as quickly as possible.”

Key preliminary results include:

• Leriglitazone significantly prevented an accumulation of iron in the brain when compared with placebo (ANCOVA p = 0.050). Iron accumulation is linked to Frataxin deficiency and was assessed by Quantitative Susceptibility Mapping (QSM). These results demonstrate that leriglitazone directly modulates the frataxin pathway.
• Magnetic Resonance Spectroscopy (MRS) shows an improvement in the metabolic biomarkers related to mitochondrial function in the spinal cord.
• Composite Cerebellar Function Severity scale (CCFS) showed that leriglitazone prevented decline in upper limb ataxia when compared with placebo. This effect is aligned with the observed MRS and QSM changes and patients treated with leriglitazone showed a consistent improvement in these three quantitative objective assessments (O’Brien test, Wilcoxon p = 0.043).
• A determination of changes in the spinal cord area, the primary outcome, were inconclusive in results from the study, as no progression was observed in patients on placebo.
• Overall, Leriglitazone was well tolerated in Friedreich's ataxia patients. As expected, based on the mechanism of action of the compound, weight gain and edema were the most frequent adverse events. Importantly, no events indicating increased cardiac risk were detected in this population known to suffer from accompanying cardiomyopathy.

“Clinical results from the Minoryx Phase 2 FRAMES clinical trial are promising. Specifically, the reduction in decline in upper limb ataxia in Friedreich's ataxia patients demonstrate the potential of meaningful benefit in tackling this neurodegenerative condition,” said Professor Alexandra Durr, the principal investigator and coordinator of the FRAMES study, from the Brain and Spine Institute of La Pitié-Salpêtrière University Hospital (ICM), Paris.

Minoryx designed the Phase 2 FRAMES study to enable the identification of a FRDA patient population that would most benefit from treatment with leriglitazone. Full and detailed results from the study will be presented in the next few months. The study data are being used to design an additional confirmatory study. Minoryx plans to discuss this new study with the FDA and the EMA. Minoryx previously received orphan drug status from the FDA and the EMA and rare pediatric disease designation from the FDA for leriglitazone as a treatment for FRDA. FRAMES has received the support of the Region Wallonia, Belgium (SPW-EER).