Investigational Fatty Acid RT001 Slows ALS Progression in Pilot Study

BioJiva plans larger trial to test RT001's efficacy for people with more severe ALS

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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RT001, an investigational treatment for amyotrophic lateral sclerosis (ALS), shows promising signs that it can slow disease progression, particularly among patients with more severe disease, according to data from a completed Phase 2 pilot trial.

While these findings indicate improvements in patients on RT001 treatment, statistical significance was not achieved due to the small number of participants included in the study. BioJiva is now planning a larger clinical trial to confirm RT001’s efficacy in people with more severe ALS.

“The promising signal of clinical benefit shown in this study with RT001 in a small group of ALS patients, combined with the continued demonstration of the well tolerated nature of the treatment, provides support for considering a larger clinical trial,” Leonard H. van den Berg, MD, PhD, the study’s lead investigator, said in a company press release.

Van den Berg is also a professor of neurology at University Medical Center Utrecht, in the Netherlands, director of the Netherlands ALS Center, and chairman of the TRICALS research initiative.

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“Additionally, the study data suggest that patients with more severe ALS may have a higher likelihood of benefitting from RT001 treatment, which provides important context for considering the design and enrollment criteria for the next clinical trial,” van den Berg added.

ALS is marked by high levels of oxidative stress, in which there is an imbalance between the production of toxic reactive oxygen species and the body’s ability to detoxify them. These molecules are toxic and contribute to the degradation of multiple tissues and cells.

Lipid peroxidation, a process that contributes to neurodegeneration in ALS, occurs when these free radicals attack fats and lead to their breakdown. Linoleic acid, also known as omega-6 fatty acid, is a dietary fat found in cellular membranes that is particularly vulnerable to this process.

What is RT001?

RT001 is a man-made version of linoleic acid that was designed to be more stable and resistant to lipid peroxidation than the naturally occurring molecule. It is incorporated in cell membranes and is expected to make cells less vulnerable to damage and protect them from degeneration.

The orally available molecule was originally developed by Retrotrope, which was acquired by BioJiva under a bankruptcy proceeding.

The pilot Phase 2 study (NCT04762589), conducted at four ALS centers in Europe, evaluated the safety and effectiveness of daily RT001 in ALS patients, ages 20 to 75, who had been diagnosed within the last three years and could perform their daily activities without assistance.

Participants were randomly assigned to receive RT001 or a placebo: three 960 mg capsules three times per day for one month, followed by three capsules twice daily for the next five months. The placebo group received capsules containing sunflower oil, a dietary omega-6 fatty acid.

Of 43 enrolled participants, 39 completed the six-month trial, and 32 opted to enter an extension phase in which all received RT001 for another six months.

The trial’s main goal was to assess changes in functional status, as measured by the revised ALS Functional Rating Scale (ALSFRS-R), after six months of treatment. A lower ALSFRS-R score reflects a greater degree of disability.

What did the study find?

Results showed that patients on RT001 experienced a slower functional decline from baseline (study start) compared with those in the placebo group. Specifically, RT001 patients showed a 3.3-point reduction, or worsening, in ALSFRS-R scores during the six-month period, whereas the placebo group declined by 4.6 points.

Similarly, treated patients experienced slower declines in the 40-item ALS assessment questionnaire (ALSAQ40), a self-reported measure of disability and a key secondary goal in the trial. Those patients experienced a 13.3-point increase, or worsening, in ALSAQ40 scores, compared with an increase of 17.2 points in the placebo group.

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The study included 33 patients with severe disease, defined as a baseline ALSFRS-R of less than 41 and an ALSAQ40 of less than 20. Among these participants, the difference in disease progression between RT001 and a placebo was more pronounced, with treated patients experiencing a 3.4-point reduction from baseline compared with 6.3 points in the placebo group.

Benefits of RT001 were still evident at 12 months, with patients who continued into the extension part demonstrating a mean decrease in ALSFRS-R of 7.2 points over one year. By comparison, untreated ALS patients would be expected to decline by 10.1 points after 12 months, based on historical data taken from the PRO ACT database which contains findings from previous ALS trials.

For the 14 patients with severe disease who completed the full year, the 12-month ALSFRS-R reduction was 5.6 points, indicating an even slower disease progression among this subset, according to BioJiva.

“We conducted this trial with the dual goals of better understanding the manner in which RT001 may potentially impact the progression of ALS and detecting a signal of therapeutic benefit for patients receiving the treatment,” said Mark G. Midei, MD, BioJiva’s vice president for medical affairs.

“The learnings from this study position us to continue development of RT001 for ALS, advancing next to a larger, statistically powered study focused on the more severe patient population that appears more likely to benefit from the treatment,” Midei said.