Leriglitazone is being investigated as a potential treatment for adrenomyeloneuropathy (AMN) and childhood cerebral adrenoleukodystrophy (CALD), the two main clinical subtypes of ALD. Existing ALD treatments are only for the treatment of CALD.
The European Medicines Agency (EMA) granted leriglitazone orphan drug designation in 2016, and the U. S. Food and Drug Administration (FDA) in 2017. The FDA also granted leriglitazone fast track designation in January 2020.
How does leriglitazone work?
Leriglitazone is a PPAR-gamma agonist or a molecule that activates PPAR-gamma. PPAR-gamma is a protein that regulates the activity of genes involved in glucose and lipid metabolism and inflammation. Leriglitazone is a synthetic compound that binds to and activates PPAR-gamma.
ALD is caused by a mutation in the ABCD1 gene, leading to the accumulation of a compound called saturated very-long-chain fatty acid (VLCFA) in the blood and central nervous system. VLCFA accumulation triggers an inflammatory response, which causes the destruction of myelin, the protective sheath that insulates nerve cells in the brain. Leriglitazone is thought to protect nerve cells by stimulating anti-inflammatory and inhibiting pro-inflammatory genes, resulting in less inflammation and oxidative stress, and overall improved cellular function.
Leriglitazone in clinical trials
A Phase 1 clinical trial in healthy male volunteers showed that leriglitazone is well-tolerated and safe. No serious adverse events occurred, even at higher doses. The trial confirmed that leriglitazone penetrates the brain and is active.
Following the successful completion of the Phase 1 trial, Minoryx started a randomized, placebo-controlled Phase 2/3 clinical trial (NCT03231878), called ADVANCE, to evaluate the efficacy of leriglitazone on the progression of AMN. This is a multi-center trial, with patients being treated in Spain, France, Hungary, Germany, Italy, the U.K., the Netherlands, and the U.S.
The efficacy of the treatment will be evaluated by measuring the ability of the patients to stand and walk as indicators of motor function. Efficacy and safety will be assessed every 24 weeks, in addition to two safety assessments after four and 12 weeks. After 96 weeks, participants will have the possibility to enter an open-label extension phase.
The randomization of 116 participants was completed in December 2018, and results are expected in October 2020.
Last updated: Jan. 14, 2020
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