WALTHAM, Mass.–The U.S. Food and Drug Administration has granted Orphan Drug designation to Affinia Therapeutics’ AFTX-201 for the treatment of BAG3-associated dilated cardiomyopathy, a rare genetic heart disease that can lead to progressive heart failure and premature death.
AFTX-201 is an investigational gene therapy designed to address the underlying genetic cause of BAG3-associated dilated cardiomyopathy, or DCM. The treatment is administered through a one-time intravenous infusion and is intended to deliver a functional BAG3 transgene to heart cells.
Affinia said the therapy uses the company’s proprietary adeno-associated virus capsid, which is designed to deliver the gene efficiently to the heart at doses five to 10 times lower than those used by traditional gene therapies employing conventional capsids such as AAV9 or AAVrh74.
In preclinical animal studies, AFTX-201 increased BAG3 protein levels in the heart, restored cardiac function and reversed structural abnormalities associated with the disease, according to the company. A survival benefit was also observed.
AFTX-201 is being evaluated in the Phase 1/2 UPBEAT clinical trial, which is actively recruiting patients at multiple sites in the United States and Canada. The study is assessing the safety and efficacy of the therapy in adults ages 18 to 55 with BAG3-associated DCM who have difficulty performing everyday physical activities because of heart failure.
“Receiving Orphan Drug designation, in addition to the recent Fast Track designation, from the FDA marks a significant achievement for the AFTX-201 program and we thank the FDA for their decision,” said Hideo Makimura, M.D., Ph.D., Chief Medical Officer at Affinia. “AFTX-201 is designed to address the underlying root cause of BAG3 DCM. The UPBEAT clinical trial is actively recruiting at multiple institutions and we look forward to continue progressing the AFTX-201 clinical program so that we can bring this potentially transformative treatment to people living with BAG3 DCM.”
BAG3-associated DCM is caused by a genetic mutation that reduces the production of BAG3 protein in cardiomyocytes, the muscle cells responsible for heart contractions. The condition can cause early-onset progressive heart failure, reduced quality of life and shorter survival despite currently available treatments.
Published research estimates that BAG3 mutations account for about 2.3% to 3.6% of DCM cases worldwide. There are currently no approved therapies that directly address the disease’s underlying genetic mechanism.
“BAG3 DCM is a devastating heart disease with a known genetic cause. It is a condition that leads to early onset, progressive heart failure, and premature death, with no approved treatment that addresses the underlying mechanism. The DCM Foundation and Genetic Cardiomyopathy Awareness Consortium commend the FDA for awarding Orphan Drug designation to AFTX-201 for the treatment of BAG3-associated DCM, acknowledging the pressing demand for innovative treatment alternatives for rare diseases like BAG3 DCM for which there remains significant unmet medical need,” said Greg Ruf, Founder and Executive Director, the DCM Foundation.
The FDA grants Orphan Drug designation to therapies intended to treat rare diseases affecting fewer than 200,000 people in the United States. The designation provides development and commercial incentives, including potential tax credits for qualified clinical trial costs, exemption from certain FDA application fees and up to seven years of market exclusivity if the therapy is approved.
