FDA Grants Breakthrough Therapy Designation for Investigational Treatment for Vanishing White Matter Disease

Calico Life Sciences (South San Francisco, CA) announced that the Food and Drug Administration (FDA) granted Breakthrough Therapy designation to fosigotifator for the treatment of vanishing white matter (VWM) disease. Fosigotifator is an investigational eIF2B activator currently undergoing evaluation in a phase 1b/2 clinical trial (NCT05757141) for safety, tolerability, pharmacokinetics, and exploratory efficacy in adult, pediatric, and infant participants with VWM disease.

Breakthrough Therapy designation is intended to expedite development and review of drugs for serious or life-threatening diseases when preliminary clinical evidence suggests the therapy may demonstrate substantial improvement over existing treatments on one or more clinically significant end points. Previously, Calico Life Sciences announced that fosigotifator had been selected for the FDA’s Support for Clinical Trials Advancing Rare Disease Therapeutics program, which is intended to support development of treatments for rare diseases.

VWM disease is an ultra-rare, progressive leukoencephalopathy caused by variants in any of the 5 subunits of eIF2B, an enzyme involved in protein synthesis and regulation of the integrated stress response. Reduced eIF2B activity can lead to chronic activation of the integrated stress response, contributing to degeneration of brain white matter. Symptoms may include impaired movement, cognitive decline, and seizures, and disease progression can be accelerated by physiologic stressors such as fever, infection, or mild head trauma.

Fosigotifator Development Program

• Fosigotifator is designed to target eIF2B and regulate the integrated stress response.
• The ongoing phase 1b/2 study is the first clinical trial of an eIF2B activator in people with VWM disease, according to Calico.
• Preclinical studies in VWM disease models showed effects on integrated stress response activity in the brain and spinal cord, as well as improvements in coordination, movement, and survival.
• Clinical studies are evaluating whether this mechanism can translate into benefit for people with VWM disease.

Source

Calico Life Sciences. Calico Life Sciences announces fosigotifator granted Breakthrough Therapy Designation by the U.S. FDA for the treatment of vanishing white matter disease. News release. Published June 23, 2026. Accessed June 23, 2026. https://www.prnewswire.com/news-releases/calico-life-sciences-announces-fosigotifator-granted-breakthrough-therapy-designation-by-the-us-fda-for-the-treatment-of-vanishing-white-matter-disease-302807202.html