Fasudil Shows Promising Results in 3 ALS Patients Treated Under Compassionate Use

Fasudil, approved in Japan for treating stroke patients, also is well-tolerated and prevents disease worsening in people with amyotrophic lateral sclerosis (ALS), according to a report of three patients who received the medicine under compassionate use.

However, the effects were transient, and all three patients experienced either a decline in their ability to perform daily activities or a deterioration in muscle function a few months after stopping treatment.

The study, “Compassionate Use of the ROCK Inhibitor Fasudil in Three Patients With Amyotrophic Lateral Sclerosis,” was published in the journal Frontiers in Neurology.

Treatments for ALS are scarce and provide only mild benefits to patients. The two approved therapies, riluzole (marketed under different brand names depending on how it is administered) and Radicava (edaravone), were approved based on a three-month survival benefit and a slowing in functional decline by 30%, respectively.

This means that disease continues to progress and to induce declines in motor function even while patients are receiving treatment. Therapies that more effectively prevent disease progression are needed for this population.

In certain situations, the drug-regulating agencies allow companies to provide experimental medicines to people outside of clinical trials. This is known as compassionate use.

Fasudil, marketed as Eril by Asahi Kasei Pharma, is an inhibitor of the Rho kinase (ROCK) protein that is approved for alleviating brain vasoconstriction in people who experienced a type of stroke called a subarachnoid hemorrhage. But animals studies in neurodegenerative diseases suggest it  also can prevent nerve cell death, foster neuronal regeneration, and modulate microglia (the brain’s immune cells) to acquire protective rather than harmful functions.

In preclinical animal models of ALS, fasudil significantly increased survival and improved motor function and regeneration of the connections between nerve and muscle cells.

“Given the promising results of Fasudil treatment in preclinical animal models of ALS and its well-known safety profile for other indications it represents an excellent candidate for re-purposing as a disease-modifying therapy in ALS,” the researchers explained.

An international team of researchers now report the safety and preliminary signs of effectiveness of fasudil in three ALS patients who received the medicine under compassionate use. All were treated with a 30 mg dose (the highest approved in Japan), given as into-the-vein infusions, twice daily for 20 consecutive working days.

The patients, a 66-year-old man and two women ages 62 and 68, all had experienced a worsening in their symptoms in the months prior to beginning fasudil, despite treatment with riluzole. One patient had seen his ALS functional rating scale-revised (ALSFRS-R) score decline from 41 to 38 points in the prior month.

This scale measures a patient’s ability to perform daily life tasks, like speaking, swallowing, and dressing. Usually, patients experience a decline of one point each month. His lung function also was severely impaired.

Notably, fasudil infusions were well-tolerated by all three patients, with none experiencing an adverse side effect — not even a drop in blood pressure, which is a frequent side effect of fasudil.

ALSFRS-R scores remained stable in all patients during the four weeks of treatment, but then started to decline a few months after fasudil was stopped. The male patient also saw his lung function improve remarkably — from 26% to 62% — but that, too, worsened severely after the treatment was discontinued.

Despite the promising results, “no conclusions with regards to efficacy of the treatment can be drawn from these single patients,” the researchers warned, explaining that it is impossible to know for sure if fasudil diminished disease progression.

“It is impossible to say whether progression was attenuated compared to the natural course of the disease. There were, however, several signs of a possible transient positive effect of Fasudil,” they wrote.

An ongoing Phase 2a trial (NCT03792490) is ongoing to confirm the benefits of fasudil in about 120 ALS patients. Named ROCK-ALS, the study is primarily designed to examine the safety of two different doses of fasudil (30 mg and 60 mg) versus a placebo.

Secondary measures include survival, change in ALSFRS-R scores, patient-reported quality of life, cognitive function, lung function, and communication between nerve cells and muscle cells.

The trial is recruiting participants across 16 sites in Germany, France, and Switzerland. More information about locations and eligibility is available here.