recently reported 48-week clinical data for its proof-of-concept open-label study in 4 ALS patients indicating that treatment with COYA 302 appeared to significantly ameliorate disease progression (stopping progression in all patients at 24 weeks with minimal decline at 48 weeks.) This was in a patient cohort who was declining prior to entry into the study.
Four ALS patients with a mean decline of -1.1 points/month in the Revised ALS Functional Rating Scale (ALSFRS-R) score prior to study initiation, were treated for 48 consecutive weeks with COYA 302 and were evaluated for safety and tolerability, Treg suppressive function, serum biomarkers of oxidative stress and inflammation, and clinical functioning as measured by the ALSFRS-R scale. Following the administration of COYA 302 for 48 weeks, patients were evaluated over an 8-week washout period.
During the 48-week treatment period, COYA 302 appeared to be well tolerated. The most common adverse event was mild injection-site reactions. No patient discontinued the study, and no deaths or other serious adverse events were reported.
Preliminary efficacy of COYA 302 was measured by the ALSFRS-R scale, a validated rating tool for monitoring the progression of disability in patients with ALS. The mean (±SD) ALSFRS-R scores at week 24 (33.75 ±3.3) and week 48 (32 ±7.8) after initiation of treatment with COYA 302 were not statistically different compared to the ALSFRS-R score at baseline (33.5 ±5.9), indicating significant amelioration in the progression of the disease over the 48-week treatment period.
Treg suppressive function, expressed as percentage of inhibition of proinflammatory T cell proliferation, showed a statistically significant increase over the course of the treatment period and was significantly reduced at the end of the 8-week washout post-treatment period. Treg suppressive function at 24 weeks (79.9±9.6) and 48 weeks (89.5±4.1) were significantly higher compared to baseline (62.1±8.1) (p<0.01), suggesting enhanced and durable Treg suppressive function over the course of treatment. In contrast, Treg suppressive function (mean ±SD) was significantly decreased at the end of the 8-week washout period compared to end-of-treatment at week 48 (70.3±8.1 vs. 89.5±4.1, p <0.05).
The study also evaluated serum biomarkers of inflammation, oxidative stress, and lipid peroxides. The available data up to 16 weeks after initiation of treatment suggest a decrease of these biomarker levels, which is consistent with the observed enhancement of Treg function. The evaluation of the full biomarker data is ongoing.