Calico Life Sciences, in collaboration with AbbVie, has had its investigational eIF2B activator fosigotifator (ABBV‑CLS‑7262) accepted into the U.S. FDA’s Support for clinical Trials Advancing Rare disease Therapeutics (START) Pilot Program, according to the company.
The FDA initiative, managed by its Center for Biologics Evaluation and Research and Center for Drug Evaluation and Research, aims to accelerate rare disease drug development by offering participating companies enhanced communication and guidance on clinical study design, patient populations and control groups.
Fosigotifator is being developed as a potential treatment for Vanishing White Matter (VWM) disease, an ultra‑rare progressive leukoencephalopathy caused by mutations in the eIF2B enzyme complex. These mutations impair protein synthesis regulation via chronic activation of the integrated stress response, leading to degeneration of brain white matter and symptoms including motor impairment, cognitive decline and seizures.
Calico and AbbVie are currently conducting a Phase 1b/2 trial assessing safety, tolerability and pharmacokinetics of fosigotifator in individuals with VWM disease. This marks the first human study of an eIF2B activator for this condition.
Preclinical data in mouse models indicate that fosigotifator reduces chronic integrated stress response in brain and spinal cord cells and improves motor coordination.
The company highlighted the FDA selection as recognition of the drug’s potential to address unmet medical needs for patients with VWM disease.
If successful, fosigotifator will advance rare disease therapeutics by demonstrating a mechanism-based strategy in human trials, supported by FDA guidance through the START pilot.
