FDA Adds Calico Life Sciences – AbbVie Program to START

Rare Daily Staff

The U.S. Food and Drug Administration selected Calico Life Sciences’ and AbbVie’s experimental therapy for vanishing white matter disease fosigotifator for the FDA START Pilot Program.

The Calico-AbbVie program joins Mytelle’s experimental gene therapy for Canavan disease, Moderna’s experimental mRNA therapy for methylmalonic acidemia, Neurogene’s NGN-401 gene therapy for Rett Syndrome, Grace Science’s GS-100 gene therapy for NGLY1 Deficiency, Denali Therapeutics’ enzyme replacement therapy DNL126 for the potential treatment of MPS IIIA (Sanfilippo syndrome type A), and Larimar Therapeutics’ experimental therapy nomlabofusp for Friedreich’s ataxia as participants the agency selected for the program.

The START pilot program was launched by the FDA in September 2023 intended to treat a rare disease or other serious condition with high unmet medical need through an enhanced mechanism for communication with the FDA.

Sponsors selected can benefit from more frequent and rapid ad-hoc interactions with the FDA to help facilitate the development of programs to the pivotal clinical study or pre-BLA meeting stage, and to generate high-quality and reliable data intended to support a BLA or New Drug Application.

Vanishing white matter disease (VWM) disease is an ultra-rare progressive leukoencephalopathy—a disease of the brain’s white matter—caused by variations in any of the five subunits of an essential enzyme in cells called eIF2B. VWM variations in eIF2B cause a reduction in its enzymatic activity that may lead to chronic activation of the integrated stress response (ISR). The ISR plays a critical role in protein homeostasis and organismal resilience, both of which are implicated in the biology of aging.

In VWM, chronic activation of the ISR in the brain causes the white matter to degenerate. Individuals with VWM disease commonly have symptoms such as impaired muscle movement, cognitive decline, seizures, and have a shortened lifespan. While symptoms often begin to appear between ages 2 and 6, the disease can present at any age. The disease course is chronic and progressive, and stressors such as fever, infection, and mild head trauma may cause episodes of rapid deterioration. There is currently no cure and no treatment approved for VWM disease.

Fosigotifator targets eIF2B, a guanine nucleotide exchange factor that is essential for protein synthesis and a key regulator of the ISR. In preclinical studies in a mouse model of VWM, fosigotifator blunted the persistent ISR in the brain and spinal cord, primarily in cell types that are known to be severely affected by the human form of VWM, and corrected coordination and movement problems in these mice.

Calico and AbbVie are currently conducting a phase 1b/2 trial of fosigotifator to evaluate the safety, tolerability, and pharmacokinetics of fosigotifator in participants diagnosed with VWM disease. This study is the first time an eIF2B activator has been administered to people with VWM disease.

Fosigotifator is also being investigated as a potential treatment for people with amyotrophic lateral sclerosis (ALS) in two ongoing studies.

“The inclusion of fosigotifator underscores the potential of this investigational therapy in addressing the unmet needs of individuals and families affected by vanishing white matter disease,” said Arthur Levinson, founder and CEO of Calico.