Phase 2 trial of ROCK inhibitor Bravyl now fully enrolled
Results expected by mid-2025, Woolsey says
A Phase 2a clinical trial testing Rho kinase (ROCK) inhibitor Bravyl (oral fasudil) in people with amyotrophic lateral sclerosis (ALS) has completed patient enrollment for its high-dose group, the company said.
While the REAL trial (NTC05218668) was initially slated to only test a 180 mg daily dose of the oral treatment, positive safety and efficacy findings from that group prompted Woolsey Pharmaceuticals to reopen the study and investigate the possible benefits of a 300 mg dose. Results are expected by the middle of next year.
“Experience with this higher dose in ALS patients will be invaluable as we progress to a larger study,” Sven Jacobson, Woolsey’s CEO, said in a company press release.
People with ALS often have elevated blood levels of ROCK, an enzyme that promotes inflammation and cell death and counteracts nerve cell regeneration. ROCK inhibitors are a class of medications expected to be able to combat these processes and reduce nerve cell death, thereby offering therapeutic potential for ALS and other neurodegenerative conditions.
ROCK inhibitor aims to slow disease progression
Fasudil is a ROCK inhibitor that’s approved in Japan for certain types of stroke, and preclinical research has indicated it may have therapeutic potential for slowing the progression of ALS.
Bravyl is Woolsey’s oral formulation of fasudil. The company recently received three U.S. patents related to it, covering the use of oral fasudil for slowing the progression of sporadic ALS, as well as solid and liquid formulations of the medication for people with swallowing difficulties, or dysphagia, a common ALS symptom.
The REAL study is testing Bravyl’s safety and efficacy in people with ALS. In its first part, 31 participants received a daily 180 mg dose of Bravyl for six months.
Results showed that levels of neurofilament light chain (NfL), a biomarker of nerve damage, significantly decreased, by 15% after six months of treatment. Greater decreases in NfL were associated with slower declines on the ALS Functional Rating Scale -Revised (ALSFRS-R), a standard clinical measure of disease progression.
Treated patients tended to see clinical improvements relative to an external group of untreated patients from an ALS database, including a 17% slower deterioration in ALSFRS-R scores, 37% slower declines in lung function, and 56% slower declines in muscle strength.
These results prompted Woolsey to enroll a second group of patients who are all receiving the higher 300 mg daily dose. Findings from this group will inform the optimal dose for future clinical trials.
Participants in each dosing group will then be able to continue receiving Bravyl for up to 2.5 more years in an open-label extension phase after they complete the main six month trial.
Data collected elsewhere also support the idea that fasudil may be of therapeutic benefit in ALS. Those include findings from an investigator-initiated Phase 2 trial called ROCK-ALS (NCT03792490) that were recently published in The Lancet Neurology.
ROCK-ALS tested the safety and efficacy of a fasudil formulation that’s administered directly into the vein using a specialized pump. A total of 120 people with early-stage ALS received either that formulation or a placebo, once daily for 20 days, on top of standard ALS therapies.
Data showed that the treatment was well tolerated and significantly preserved motor neurons relative to a placebo. Motor neurons are the nerve cells responsible for coordinating voluntary movements that are progressively lost in ALS.
The treatment also tended to be associated with slower declines in lung function among trial participants, although this was only significant in women at the 60 mg fasudil dose.
Other outcome measures, including ALSFRS-R scores, NfL levels, and survival, did not significantly differ between groups, which the researchers noted “was not unexpected because of the short treatment duration.”
Although this trial didn’t specifically test the Bravyl formulation, Jacobson noted that such data are, “very encouraging” for Woolsey’s ongoing research into the use of oral fasudil for ALS.
The findings will also support Raya Therapeutic‘s development of RT1968, another version of fasudil. The company has said that based on positive findings from ROCK-ALS, it was planning more extensive clinical studies with larger groups of ALS patients.
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