Calico, Alphabet's anti-aging company, has announced disappointing results from the Phase 3 trial of its investigational drug, fosigotifator, in patients with amyotrophic lateral sclerosis (ALS). The drug, which targets the integrated stress response (ISR), failed to meet its primary and secondary endpoints in the HEALEY ALS Platform Trial.
The multi-center, randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of fosigotifator over a 24-week period. The primary endpoint was to assess the effect of fosigotifator on disease progression, combining function and mortality measures. Secondary endpoints included the revised ALS Functional Rating Scale (ALSFRS-R), respiratory function, and health-related quality of life.
The results indicated that fosigotifator did not demonstrate a statistically significant effect on disease progression compared to the placebo group. Furthermore, no significant improvements were observed in secondary endpoints, including respiratory function and quality of life. However, an exploratory high-dose group showed a potential signal in muscle strength, with slower deterioration in both upper and lower extremities.
"Although these results were disappointing, the study has yielded important insights into fosigotifator’s potential bioactivity in people with ALS that supports further investigation," said Bill Cho, head of clinical sciences at Calico, in a press release. "We remain committed to investigating the potential of fosigotifator as a much needed treatment option for people living with ALS and for other disorders, including vanishing white matter disease and major depressive disorder which each test different scientific hypotheses."
ALS is a progressive neurodegenerative disease affecting nerve cells in the brain and spinal cord, leading to muscle weakness, paralysis, and ultimately, respiratory failure. There is currently no cure for ALS, and available treatments offer limited benefits in slowing disease progression.
Fosigotifator is designed to modulate the integrated stress response (ISR), a cellular pathway activated in response to various stressors. By targeting the ISR, the drug aims to restore cellular homeostasis and prevent further neuronal damage. The FDA had previously selected fosigotifator for its START Pilot Program, aimed at accelerating its development as a treatment for vanishing white matter disease.
Despite the setback in ALS, Calico plans to continue investigating fosigotifator for other indications, including vanishing white matter disease and major depressive disorder. Further studies will be needed to fully elucidate the potential therapeutic benefits of fosigotifator in these conditions.
