Patient recruitment has concluded for the high-dose cohort of a Phase 2 clinical trial (NCT05218668) investigating oral fasudil (Bravyl; Woolsey Pharmaceuticals) as a potential treatment for amyotrophic lateral sclerosis (ALS). The study, designed to evaluate the safety and efficacy of fasudil, a Rho-associated kinase (ROCK) inhibitor, anticipates releasing results from the high-dose arm by mid-2025.
The high-dose cohort, referred to as REAL, includes 31 participants diagnosed with probable or definite ALS according to the El Escorial Revised ALS diagnostic criteria. Participants in this cohort will receive 300 mg/day of oral fasudil. The primary outcome of the study is safety, assessed by the incidence of adverse events (AEs) and serious AEs. Secondary outcomes include changes in the ALS Functional Rating Scale-Revised (ALSFRS-R), slow vital capacity (SVC), and the rate of decline in muscle strength.
Promising Results from Low-Dose Cohort
Data from the low-dose cohort (180 mg/day) of fasudil demonstrated encouraging results on biomarkers associated with ALS progression. Patients in this group experienced a 15% reduction in neurofilament light (NfL), a marker of neuroaxonal damage, over a six-month treatment period. Furthermore, compared to a matched historical control group, the low-dose cohort exhibited a 17% smaller decline in ALSFRS-R, a 37% smaller decline in SVC, and a 56% smaller decline in muscle strength. Notably, reductions in NfL correlated with less deterioration on the ALSFRS-R (P = .028).
Insights from Woolsey Pharmaceuticals
"Experience with this higher dose in ALS patients will be invaluable as we progress to a larger study," stated Sven Jacobson, chief executive officer at Woolsey Pharmaceuticals. "Furthermore, recently published results from a university-led, three-arm, double-blind study of fasudil in patients with ALS found a relationship between dose and improved motor neuron function, which is very encouraging for our ongoing research."
Previous Phase 2 Trial: ROCK-ALS
Fasudil was previously assessed in the ROCK-ALS trial (NCT03792490), a Phase 2 study published in The Lancet Neurology. This double-blind, placebo-controlled trial included 35 patients in the fasudil 30 mg group, 39 in the fasudil 60 mg group, and 44 in the placebo group. The study found that fasudil was safe and well-tolerated over the four-week treatment period, with AEs primarily related to disease progression.
Data from the ROCK-ALS study indicated that the estimated proportion without a drug-related serious AE was 1.00 (95% CI, 0.91-1.00) with placebo, 1.00 (0.89-1.00) with fasudil 30 mg, and 1.00 (0.90-1.00) with fasudil 60 mg. Treatment tolerability was 0.93 (95% CI 0.81-0.99) with placebo, 1.00 (0.90-1.00) with fasudil 30 mg, and 0.90 (0.76-0.97) with fasudil 60 mg. Survival outcomes did not significantly differ across treatment groups. However, exploratory analysis revealed a significant reduction in serum glial fibrillary acidic protein (GFAP) on day 180 in the fasudil 60 mg group (0.75; 95% CI, 0.60-0.95) compared to placebo (0.90; 95% CI, 0.75-1.08; P = .041).
