Reneo Suspends Development of Mavodelpar After Pivotal Study in PMM Misses

Rare Daily Staff

Reneo Pharmaceuticals reported its pivotal STRIDE study of its experimental therapy mavodelpar in adult patients with primary mitochondrial myopathies did not meet its primary efficacy or secondary efficacy endpoint.

The primary efficacy endpoint of the trial was the change from baseline in the distance walked during the 12-minute walk test (12MWT) at week 24. The secondary efficacy endpoint was the change from baseline in the PROMIS Short Form Fatigue 13a score.

Primary mitochondrial myopathies (PMM) are a group of rare, genetic metabolic disorders caused by mutations or deletions in the mtDNA or nDNA. These genetic alterations hamper the ability of mitochondria to generate energy from nutrient sources, resulting in energy deficits that are most pronounced in tissues with high energy demand such as muscle, brain, and heart. The symptoms of PMM include muscle weakness, exercise intolerance, movement disorder, deafness, blindness, and droopy eyelids among others. The prognosis for these disorders ranges in severity from progressive weakness to death.

Mavodelpar (REN001) is a potent and selective peroxisome proliferator-activated receptor delta (PPARδ) agonist which has been studied in two rare genetic mitochondrial diseases that typically present with myopathy and have high unmet medical needs: PMM and long-chain fatty acid oxidation disorder.

The STRIDE study was a global, randomized, double-blind, placebo-controlled pivotal phase 2b trial of mavodelpar in adult patients with PMM due to mitochondrial DNA (mtDNA) defects. The study was designed to investigate the efficacy and safety of 100 mg mavodelpar administered once-daily over a 24-week period.

The STRIDE AHEAD study was an open-label extension (OLE) trial being conducted outside of the United States in adult patients with PMM due to mtDNA defects who participated in the STRIDE study, the mavodelpar phase 1b study, and mavodelpar-naïve patients with PMM due to nuclear DNA (nDNA) defects. The study was designed to evaluate the long-term safety and tolerability of 100 mg mavodelpar administered once-daily over a 24-month period.

The company intends to implement immediate cost savings initiatives, including suspension of the ongoing STRIDE AHEAD study and all other mavodelpar development activities and a workforce reduction of approximately 70 percent. The company currently has over $100 million in cash, cash equivalents, and short-term investments.

“Although the results of the STRIDE study were negative, the data generated are vitally important to the scientific community and we will make these data available once the final analyses are complete,” said Gregory Flesher, president and CEO of Reneo Pharmaceuticals.

Photo: Gregory Flesher, president and CEO of Reneo Pharmaceuticals