Fasudil safe, preserves motor neurons in early-stage ALS: Study

Raya also developed a version of drug for patients with difficulty swallowing

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Treatment with fasudil (RT1968), which Raya Therapeutic is testing for amyotrophic lateral sclerosis (ALS), was safe and outperformed a placebo at preserving motor neurons in adults with early-stage disease.

That’s according to data from ROCK-ALS (NCT03792490), an investigator-led Phase 2a trial that tested how safe fasudil is when given intravenously, or into the vein, and whether it improved clinical outcomes against a placebo in 120 patients.

Building on these data, Raya plans to launch more extensive clinical studies involving larger groups of patients. The company also developed a version of fasudil that’s easier to administer for patients who have difficulty swallowing.

“We are excited by the encouraging data from the ROCK-ALS trial of fasudil and remain steadfast in our mission to develop breakthrough therapies for ALS and other neurodegenerative disorders,” Anjan Aralihalli, Raya’s president and founder, said in a company press release.

The data were presented in at the European Network to Cure ALS (ENCALS) annual meeting, which took place June 17-20 in Stockholm.

ALS causes damage to motor neurons, the nerve cells that control voluntary movements such as walking and talking. Over time, muscle weakness gets progressively worse, leading to symptoms such as difficulty swallowing and breathing.

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Fasudil’s effect on motor neurons in ALS

Fasudil inhibits the Rho kinase (ROCK) protein and is already approved in Japan and China for treating subarachnoid hemorrhage, an uncommon form of stroke where there’s bleeding between the brain and the membrane that covers it. It’s been suggested that inhibiting ROCK with fasudil may have benefits in neurodegenerative diseases since it also seems to prevent nerve cell growth and repair.

Preclinical studies showed fasudil helps motor neurons survive and regrow in ALS animal models, leading to better motor function and survival. It also helps reduce the activation of microglia, resident immune cells in the brain that are overactive in ALS.

The treatment was also well tolerated and slowed disease progression in ALS patients who received fasudil under compassionate use, which lets patients access a treatment that’s not yet approved and when no other option exists.

The ROCK-ALS trial, sponsored by investigators at University Medical Center Göttingen, Germany, was designed to test fasudil against a placebo in 120 adults with early ALS, or those whose symptoms started six months to two years before enrolling.

Recruitment took place at sites in Germany, France, and Switzerland, and participants were randomly assigned to receive either fasudil at 30 or 60 mg, or a placebo, given daily intravenously for 20 days. All could continue to receive standard ALS treatment with riluzole (sold as Rilutek, among others) and/or edaravone (sold as Radicava).

The trial’s main goal was to determine the treatment’s safety and tolerability. Secondary goals included changes in the motor unit number index (MUNIX), which estimates how many motor neurons are sending signals to a muscle, lung function, quality of life, survival, and overall disease progression.

No differences were seen in safety and tolerability between the groups.

At 26 days after the treatment’s start, MUNIX scores didn’t decline as much in those treated with 60 mg fasudil, suggesting preserved motor neurons, compared with the placebo group. At 90 days, or three months, the same was observed in patients treated with both fasudil doses.

There was also a trend toward slower decline in lung function in patients treated with 60 mg fasudil after 26 days. For women, this difference was significant at all points tested.

“MUNIX evaluation suggests a slower loss of motor units in fasudil-treated patients compared to placebo, suggesting a benefit of fasudil to be explored in further clinical trials,” the researchers wrote.

“We are especially grateful to our licensor, University Medical Center Göttingen (UMG), for their pivotal support and collaboration as the principal sponsor of this Phase 2 study. Their commitment and support have been instrumental in advancing fasudil for ALS patients,” Aralihalli said.