Woolsey Pharmaceuticals' Phase 2a Study of BRAVYL in ALS Shows Significant Neurofilament Light Reduction and Improved Outcomes

Woolsey Pharmaceuticals, a clinical-stage drug development company based in New York, announced on June 19, 2024, that its investigational drug, CIRARA, exhibited promising results in the REAL (Rho kinasE inhibition in Amyotrophic Lateral sclerosis) study. This study is designed to evaluate the drug's safety, tolerability, and impact on clinical outcomes and neurodegeneration biomarkers in patients with Amyotrophic Lateral Sclerosis (ALS).

The REAL study is an open-label, single-arm trial that enrolled 31 patients in its first cohort, administering a daily dose of 180 mg of CIRARA. Out of these participants, 25 completed 24 weeks of treatment, and 20 continued into the study's extension phase. The primary endpoint focused on safety, and the results showed that CIRARA was well tolerated with no drug-related adverse events leading to participant withdrawal. Additionally, no unexpected or concerning safety issues were noted even among patients treated for up to 18 months.

Crucially, the study demonstrated a significant reduction in Neurofilament Light Chain (NfL) levels, a key biomarker for neuronal damage and ALS disease progression, following 24 weeks of treatment. NfL levels are a reliable indicator of the rate of ALS progression, and reductions in these levels are associated with clinical benefits such as longer event-free survival and improved clinical outcomes measured by the ALS Functional Rating Scale – Revised (ALSFRS-R), Slow Vital Capacity (SVC), and muscle strength.

The study observed a 15% reduction in NfL from baseline to six months, a statistically significant improvement (p<0.001). Given that NfL levels in ALS patients typically increase by an average of 11% over six months, the results suggest that a 180 mg/day dose of CIRARA could potentially reduce NfL levels by up to 26% compared to a placebo. Moreover, greater reductions in NfL were correlated with less deterioration in ALSFRS-R scores (Spearman's coefficient = -0.45, p=0.028), indicating that early clinical benefits may manifest concurrently with NfL reductions.

A "propensity matched" analysis compared 12-month clinical outcomes from the REAL study with those from a matched cohort from the Ceftriaxone ALS Study database. This analysis showed a 28% improvement in the rate of ALSFRS-R deterioration (p=0.12), a 42% slower decline in SVC (p=0.05), and a 50% slower rate of muscle strength decline (p=0.06), especially in lower limb muscles which experienced a 71% reduction in weakening (p=0.04). Upper limb muscles showed a more modest 37% reduction (p=0.22). A similar analysis using the Australian MND Registry yielded comparable ALSFRS-R and SVC results, although muscle strength data were not available.

Given the positive safety and tolerability profile observed at the 180 mg/day dose, the REAL study has been expanded to screen and enroll up to 15 additional patients at a higher dose of 300 mg/day. These patients will be treated for 24 weeks, with an option for extended treatment.

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease with rapid and inevitable progression, typically resulting in death within two to five years. The ability to slow or halt disease progression represents a significant advancement in improving the prognosis and quality of life for those affected.

Woolsey Pharmaceuticals is committed to pioneering new treatments for neurodegenerative diseases, with a focus on ALS. The company aims to usher in a new era of treatment options that can save and improve the lives of patients in need.