Audentes Therapeutics announced that the U.S. Food and Drug Administration (FDA) has granted Rare Pediatric Disease and Fast Track designations for AT132, the company's gene therapy product candidate being developed to treat X-Linked Myotubular Myopathy (XLMTM). In addition to these two new designations, AT132 has also received Orphan Drug designation from both the FDA and European Medicines Agency.
"The incentives provided by the Rare Pediatric Disease and Fast Track designations are significant and include opportunities to work with FDA to expedite the development of AT132, and the potential to obtain a valuable Rare Pediatric Disease Priority Review Voucher upon approval,” Matthew R. Patterson, President and Chief Executive Officer of Audentes, said. “We are eager to leverage these benefits and to work closely with the FDA and XLMTM patient community as we pursue our goal of developing AT132 to treat this devastating rare disease."
Audentes recently announced the enrollment of the first patient in ASPIRO, the Phase 1/2 clinical trial of AT132 in patients with XLMTM. Preliminary data from ASPIRO is expected to be available in the fourth quarter of 2017. In addition to ASPIRO, the clinical development program for AT132 includes RECENSUS, a retrospective medical chart review, for which Audentes has previously announced data from an initial analysis of 112 male subjects. This analysis confirmed and expanded upon the understanding of the significant disease burden of XLMTM on patients, families and the healthcare system. Audentes is also conducting INCEPTUS, a prospective natural history and run-in study. The primary objectives of INCEPTUS are to characterize the clinical condition of children with XLMTM, identify subjects for potential enrollment in ASPIRO, and serve as a longitudinal baseline and within-patient control for ASPIRO.
A Rare Pediatric Disease designation may be granted by the FDA to drugs and biologics intended to treat orphan diseases affecting fewer than 200,000 patients in the United States, primarily age 18 years or younger. The designation provides incentives to advance the development of rare disease drugs, including access to the FDA's expedited review and approval programs. In addition, under the FDA's Rare Pediatric Disease Priority Review Voucher program, a sponsor that receives approval for a biologics license application for a rare pediatric disease may be eligible to receive a voucher for a priority review of a subsequent marketing application for a different product. The priority review voucher may be used by the sponsor, sold or transferred.
The Fast Track program was created by the FDA to facilitate the development and expedite the review of new drugs which show promise in treating a serious or life-threatening disease and address an unmet medical need. Drugs that receive this designation benefit from more frequent communications and meetings with FDA to review the drug's development plan including the design of the proposed clinical trials, use of biomarkers and the extent of data needed for approval. Drugs with Fast Track Designation may qualify for priority review to expedite the FDA review process, if relevant criteria are met.
AT132 is the Audentes product candidate being developed to treat XLMTM, a rare monogenic disease characterized by extreme muscle weakness, respiratory failure and early death, with an estimated 50% mortality rate by 18 months of age. XLMTM is caused by mutations in the MTM1 gene, which encodes a protein called myotubularin. Myotubularin plays an important role in the development, maintenance and function of skeletal muscle cells. AT132 is comprised of an AAV8 vector containing a functional copy of the MTM1 gene. Multiple studies in animal models of XLMTM have demonstrated that a single administration of AT132 improved disease symptoms and survival rates, with no significant AT132-related adverse events or safety findings.