FDA Puts RT001 on Fast Track as Possible FA Therapy

The U.S. Food and Drug Administration (FDA) has granted rare pediatric disease and fast track designations to Retrotope’s investigational therapy RT001 for the treatment of Friedreich’s ataxia (FA), the company announced in a press release.

RT001 also received orphan drug designation from the European Medicines Agency (EMA) for the treatment of infantile neuroaxonal dystrophy (INAD), another severe neurodegenerative disease.

These designations are all meant to accelerate the development of RT001. Rare pediatric disease designation qualifies the therapy for an accelerated review — typically six months, rather than a year — and the developer is given a voucher that can be exchanged for an accelerated review of a different treatment.

The fast track program is intended to accelerate the therapy’s development and expedite its approval by providing more frequent meetings with the FDA and discussions about the development plan.

The EMA’s orphan drug designation encourages the development of potential therapies for rare and serious diseases by granting them various financial and regulatory benefits. These include exemptions from certain fees, trial protocol assistance, and 10 years of market exclusivity upon approval.

“We are proud to receive these key regulatory designations for RT001 in INAD and FA, as they validate and support the important work that we are undertaking to address rare, life-threatening diseases that are impacting young people around the world,” said Vidhya Gopalakrishnan, PhD, the chief development officer of Retrotope.

RT001 is a stabilized version of a fat molecule essential for cellular membranes. It replaces natural fats, known as polyunsaturated fatty acids, in cell membranes to protect cells from oxidative stress.

Oxidative stress is suspected to be one of the primary sources of nerve cell death underlying several degenerative diseases, including Friedreich’s ataxia. It gives rise to potentially harmful reactive oxygen species, which can cause damage to fats in the membrane of cells and mitochondria, the cell’s powerhouses.

RT001 was deemed safe and well-tolerated in FA patients, and showed early signs of effectiveness, in a small Phase 1/2 clinical trial (NCT02445794).

The study enrolled a total 18 participants and assigned them randomly to receive oral RT001 — at a dose of 1.8 or 9 grams per day — or a placebo, for four weeks.

Despite the treatment’s short duration, RT001 outperformed placebo at improving fitness capacity, and showed a trend toward a slower disease progression — as measured by Friedreich’s Ataxia Rating Scale-Neurological (FARS-Neuro) scores. It all demonstrated greater walking speed and more oxygen consumption.

Following these promising results, the company launched a Phase 2/3 trial (NCT04102501) to further validate the effectiveness, and determine long-term safety and tolerability of RT001 in adults with FA.

The trial, which dosed its first patient in January 2020, assigned participants randomly to either treatment with RT001 or a placebo for 11 months. Treatment in the first month was given via nine capsules a day, followed by six daily capsules thereafter.

The primary goal is to assess the changes in peak workload, or fitness capacity, from start to end of study. Secondary measures include changes in walking distance, disease progression, fatigue, and impression of disease impact.

Complete data from this study is expected later this year.

“The entire team at FARA is grateful for the dedication that Retrotope has demonstrated in its effort to develop a novel treatment for FA,” said Farmer. We are excited that the company has completely enrolled its ongoing pivotal study of RT001 in patients with FA and look forward to the read out of data from the trial.”

Retrotope also is conducting  a pivotal Phase 2/3 trial of RT001 in patients with INAD. The first results are scheduled for release by June.