Orphan designation is given to investigative therapies with the potential to be a safe and effective treatment for rare, life-threatening or chronically debilitating conditions with no approved treatments, or for conditions with approved treatments in which the investigational therapy shows significant benefit.
These designations are designed to provide regulatory support and financial benefits, to accelerate the clinical development and review of leriglitazone, and to ensure marketing exclusivity for a period of time (seven years in the U.S. and 10 years in the European Union) upon regulatory approval.
“We are very pleased that, following the recent FDA orphan drug designation for leriglitazone in Friedreich’s ataxia, the European Commission has also granted orphan drug status, further demonstrating the potential of this novel drug candidate and our commitment to changing the lives of patients suffering from severe orphan diseases,” Marc Martinell, Minoryx’s CEO, said in a press release.
Leriglitazone is an oral therapy that works by activating PPAR gamma (γ), a receptor molecule involved in several cellular processes, including the regulation of mitochondria (the cells’ “powerhouses”) function and oxidative stress.
Oxidative stress is an imbalance between the production of potentially harmful free radicals and the cells’ antioxidant defense, which can lead to cellular damage.
Previous studies in multiple animal models of neurodegenerative disorders have shown that leriglitazone has antioxidant, anti-inflammatory, and neuroprotective properties, improving mitochondrial function, restoring energy production, and increasing nerve cell survival.
Results from a Phase 1 clinical study indicated that leriglitazone is well-tolerated and able to cross the blood-brain barrier — a protective membrane that prevents large molecules in the blood from reaching the brain. That means it has the potential to exert its effects in the central nervous system (the brain and spinal cord).
The multi-center, double-blind, Phase 2 FRAMES study (NCT03917225), which completed enrollment ahead of schedule, is evaluating the safety and effectiveness of leriglitazone in 39 FA patients, ages 12 to 60 years.
Participants — recruited in Belgium, France, Germany, and Spain — will be randomly assigned to receive either leriglitazone (15 mg/ml) or a placebo, given daily as an oral suspension, for one year.
FRAMES’s main goal is to evaluate whether leriglitazone delays or prevents disease progression — through changes in patients’ cervical spinal cord area, determined by magnetic resonance imaging scans — compared with a placebo.
Secondary goals include the assessment of leriglitazone’s safety and tolerability, as well as its effects on other clinical measures, including several FA biomarkers, functional disability scores, and patient-reported outcomes (such as fatigue and quality of life).
“Leriglitazone is our lead drug candidate currently in late-stage clinical development in a number of life-threatening orphan [central nervous system] diseases,” said Martinell.
He also noted that “patient enrollment has been completed in both the AMN and the [FA] studies and we are on track to present our results by the end of 2020.”