Potential Friedreich’s Ataxia Treatment, RT001, Shows Safety and Tolerability in Clinical Trial

Early results from Retrotope‘s Phase 1/2 clinical trial assessing RT001 as a potential treatment for Friedreich’s ataxia (FA) show that it has met it primary safety, tolerability and pharmacokinetics endpoints, the study’s lead investigator announced.

The ongoing trial, titled “A First in Human Study of RT001 in Patients with Friedreich’s Ataxia” (NCT02445794), is randomized, double-blind, 28-day study of orally dosed RT001 in 18 FA patients. It is being is conducted at the Collaborative Neuroscience Network in Long Beach, California, and at USF Ataxia Research Center in Tampa, Florida.

Biological activity was not a primary goal of the study, but the researchers tested a number of clinically important activity measures and found these to be highly correlated to disease severity scales, and showed various robust signals of RT001’s effect at one or more doses.

“It is impressive that multiple efficacy indications moved in the right direction in only 28 days in such a small study. This drug clearly deserves immediate further study in FA, which results in a slow, but steady decline in muscular and neurological function,” the investigator, Dr. Theresa Zesiewicz, said in a press release.

“This study met and exceeded all of its goals. The trial creates a profile of an extremely well-behaved drug: safe, well-tolerated at high doses, and rapidly adsorbed to target levels determined in preclinical studies,” added Curtis Scribner, MD, CMO of Retrotope.

One adverse event, uncontrolled diarrhea, was reported in a patient with very low body mass index. This event helped to establish RT001’s maximum tolerated dose level (MTD) at 9 g/day.

Fatty acid metabolites of RT001 were also found in multiple blood compartments, indicating the drug contributed to normal fatty acid processing.

Retrotope will now conduct an extension trial that will re-randomize the same patients into treatment and comparator arms for six months. The extension aims to refine the dose of RT001 under a low polyunsaturated fatty acid (PUFA) diet, and to determine the longer-term safety and durability of the drug’s clinical effects.

Friedreich’s ataxia (FA) is a rare inherited disease that causes nervous system damage and movement problems. It affects around 5,000 people in the United States, and more than 20,000 worldwide. It usually begins in childhood and leads to impaired muscle coordination (ataxia) that worsens over time. There are currently no approved treatments for FA.

RT001 is a chemically stabilized formula of a natural fatty acid that provides resistance to lipid peroxidation in cellular and mitochondrial membranes through a new method. In FA, free iron is a catalyst for lipid peroxidation of exactly the type that can be mitigated with RT001. The U.S. Food and Drug Administration (FDA) designated RT001 an Orphan Drug to advance its development as an FA therapy earlier this year.

“This study would not have been possible without the support and guidance provided by the Friedreich’s Ataxia Research Alliance (FARA) and the clinicians in its network, particularly Dr. Rob Wilson at the University of Pennsylvania Perlman School of Medicine, Dr. Susan Perlman at UCLA, and importantly, Jen Farmer and her team at FARA. … This organization makes FA trials possible and successful,” Bob Molinari, PhD, CEO of Retrotope, concluded.