Phase 2 Study of RT001 in ALS Patients Fully Enrolled, Retrotope Says

A Phase 2 clinical trial evaluating oral RT001 — Retrotope’s experimental synthetic fatty acid — as a treatment of amyotrophic lateral sclerosis (ALS) is fully enrolled, the company announced.

The enrollment target of 40 patients was met, and exceeded, ahead of its scheduled six weeks. Dosing began in this Phase 2 study (NCT04762589) in March, and Retrotope expects that trial data to be available by year’s end.

“Patients living with ALS are in need of new and improved treatment options for this devastating disease,” Caroline Ingre, MD, PhD, head of the ALS Center at Karolinska Institute in Stockholm and a clinical investigator for the study, said in a press release.

“This trial enrolled very rapidly due to the enthusiasm of ALS patients for a new potential treatment with a unique mechanism for combatting this disease. We look forward to assessing the results of this investigation later this year,” Ingre added.

RT001 is a stabilized version of a dietary fat called linoleic acid, also known as omega-6 fatty acid, that is being investigated in a range of rare neurodegenerative diseases, including ALS.

The therapy works by replacing the less-stable linoleic acid occurring naturally in cell membranes, making them less vulnerable to damage. In doing so, it aims to prevent oxidative stress (a cell’s inability to detoxify harmful molecules) and cellular degeneration arising from lipid peroxidation. Lipid peroxidation, or the oxidative degradation of fats, is known to be out of balance in ALS.

The Phase 2 study, taking place at sites in Europe, is a randomized and double-blind clinical trial evaluating the efficacy, safety, and tolerability of daily RT001 in ALS patients over a period of 24 weeks (about six months).

Participants, ages 20 to 75 and diagnosed less than three years before enrolling, will be given three, 960 mg RT001 or placebo (sunflower oil, an omega-6 fatty acid) capsules three times daily for one month, followed by three capsules twice a day for the next five months.

The study’s main goal is changes in disability, using the revised ALS Functional Rating Scale, after the six months of treatment compared with placebo. Secondary assessments include changes from the study’s start (baseline) in a composite measure of disease progression, changes in self-reported health status and in respiratory function, and side effects.

“Retrotope is grateful for the confidence shown by investigators and patients for this clinical trial of RT001 to treat ALS. We believe that the interest of the ALS community has been driven by the existing unmet medical need and the unique attributes of RT001,” said Mark Midei, MD, Retrotope’s vice president for medical affairs.

“As an oral drug, RT001 offers patients significant convenience and administration advantages over other potential treatments that require injections or infusions,” Midei said.

In previous clinical trials involving more than 100 patients with various neurodegenerative diseases, RT001 was found to be safe in daily use. Clinical work in RT001, the company reported, also includes 23 ALS patients treated for up to 24 months (two years), and demonstrated both safety and potential signs of disease slowing.

Retrotope opened an expanded access, or “compassionate use,” program for eligible patients in the U.S. in September 2018.

“The global ALS patient community remains in desperate need of effective treatments for ALS. Clinical trials like the ongoing study of RT001 from Retrotope, are essential if we are to significantly impact ALS progression or symptoms,” said Ammar Al-Chalabi, PhD, a professor of neurology and complex disease genetics at King’s College London, and director of the King’s MND Care and Research Centre, funded by the Motor Neurone Disease Association.