RARE Daily

FDA Grants Fast Track Designation to Azafaros’ Treatment for Lysosomal Storage Disorders

January 5, 2023

The U.S. Food and Drug Administration granted Fast Track designation to Azafaros’ lead experimental candidate AZ-3102 for the treatment of GM1 and GM2 gangliosidoses and Niemann-Pick disease type C.

Fast Track is a process designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill an unmet medical need.

The agency also cleared Azafaros’ Investigational New Drug application to conduct a clinical phase 2 trial for AZ-3102 for the treatment of GM2 gangliosidosis (GM2) and Niemann-Pick disease type C (NP-C).

“The IND clearance and Fast Track Designation highlight AZ-3102’s potential and demonstrate the ability of the Azafaros team to achieve our ambitious goals,” said Stefano Portolano, CEO of Azafaros.

The company expects to progress further with its phase 2 study and start phase 3 pivotal studies, two important milestones on our mission to bring novel treatment options to patients living with severe rare genetic diseases, said Portolano.

AZ-3102 is a therapeutic candidate developed for people affected by lysosomal storage disorders (LSDs) with neurological involvement. AZ-3102 is an orally available, brain penetrant azasugar, engineered to have a unique dual mode of action by inhibiting two key enzymes which modulate the metabolism of glycosphingolipids.

“GM2 gangliosidosis and Niemann-Pick disease type C are debilitating, life-shortening diseases with devastating impact on patients and their families, and there is an urgent need for new therapeutic options. AZ-3102 has unique characteristics that confer the potential to be an effective therapeutic innovation for these patients,” said Marc Patterson, professor of Neurology, Pediatrics, and Medical Genetics in the division of child neurology at the Mayo Clinic in Rochester, Minnesota, and principal investigator for the U.S. part of the study.

Azafaros’s RAINBOW phase 2 trial is a multinational, double-blind, placebo-controlled, parallel-group trial investigating the safety, tolerability, and pharmacokinetics of a once-daily oral administration of AZ-3102 for 12 weeks in GM2 and NP-C patients between 12 and 20 years of age. The study is being conducted in the U.S. as well as in other countries. The pharmacodynamics and the impact of AZ-3102 on potential disease biomarkers will also be measured during the trial.

Lysosomal storage disorders are a group of more than 70 diseases that are characterized by lysosomal dysfunction, most of which are inherited as autosomal recessive traits. These disorders are individually rare but collectively affect 1 in 5,000 live births. They typically present in infancy and childhood, although adult-onset forms also occur. They are caused by genetic mutations affecting the function of specific enzymes, transporters, receptors, or hormones involved in metabolizing and transporting the body’s building blocks such as sugars, proteins, and lipids. These malfunctions can impair either the assembly of crucial metabolic end-products which are needed for the normal function of the body or lead to harmful accumulations of intermediate metabolites.

GM1 gangliosidosis and GM2 gangliosidosis (Tay-Sachs and Sandhoff diseases) are caused by the accumulation of GM1 or GM2 gangliosides, respectively, in the central nervous system (CNS), resulting in progressive and severe neurological impairment and early death. These diseases mostly affect infants and children, and no disease-modifying treatments are currently available.

Niemann Pick disease type C (NP-C) is a progressive, life-limiting neurological condition caused by mutations in the NPC1 or NPC2 gene and aberrant endosomal-lysosomal trafficking, leading to the accumulation of various lipids, including gangliosides in the CNS. The onset of disease happens throughout the lifespan of an affected individual, from prenatal life through adulthood. The mainstay of therapy is symptom management.

Author: Rare Daily Staff

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