WALTHAM, Mass. — Affinia Therapeutics announced that the U.S. Food and Drug Administration has granted Fast Track designation to AFTX-201, an investigational gene therapy designed to treat BAG3-associated dilated cardiomyopathy (DCM), a genetic form of heart disease that can lead to heart failure.
AFTX-201 is designed to address the genetic root cause of BAG3 DCM by delivering a fully human, full-length BAG3 transgene using Affinia’s proprietary adeno-associated virus capsid engineered to efficiently target heart tissue. The company said the capsid allows effective cardiac transduction at doses five to ten times lower than gene therapies using conventional capsids such as AAV9 or AAVrh74.
The therapy is being evaluated in the UPBEAT clinical trial, a Phase 1/2 study examining the safety, tolerability and preliminary efficacy of AFTX-201 in adults with genetically confirmed BAG3-associated dilated cardiomyopathy. The treatment is administered as a single intravenous infusion.
In preclinical studies using an animal model of the disease, AFTX-201 increased BAG3 protein levels in heart tissue and restored cardiac function, according to the company.
“We are grateful to the FDA for granting the Fast Track designation to AFTX-201 as a treatment for BAG3 DCM and to the patient and physician communities for their support of our UPBEAT clinical trial,” said Hideo Makimura, M.D., Ph.D., Chief Medical Officer at Affinia. “This Fast Track designation, together with the FDA’s recent approval of our IND application for AFTX-201 and the European Medicines Agency’s designation of AFTX-201 as an Orphan Drug, strengthens our conviction that AFTX-201 has the potential to significantly improve the lives of those affected by BAG3 DCM.”
Dilated cardiomyopathy is the leading cause of heart failure in younger patients and one of the most common reasons for heart transplantation. Patients with genetically driven forms of the disease, such as those caused by mutations in the BAG3 gene, may benefit from targeted gene therapies.
“DCM is the leading cause of heart failure in young people and the most frequent indication for heart transplantation despite current treatments,” said Greg Ruf, Founder and Executive Director of the DCM Foundation. “People whose DCM is caused by a genetic mutation such as BAG3 may benefit from a gene therapy approach.”
Fast Track designation is intended to accelerate the development and review of therapies that address serious conditions and unmet medical needs. The designation allows for more frequent communication with the FDA, the potential for rolling review of a future marketing application, and eligibility for accelerated approval or priority review if certain criteria are met.
The UPBEAT clinical trial is a multicenter, single-arm, open-label Phase 1/2 study evaluating AFTX-201 in adults with genetically confirmed BAG3-associated dilated cardiomyopathy. The trial includes a dose-exploration phase followed by a dose-expansion phase, with all participants receiving a single intravenous infusion of the therapy at doses determined to be safe and effective based on preclinical research.
The primary objective of the study is to evaluate safety and tolerability through 52 weeks following administration. Secondary and exploratory endpoints include pharmacodynamic measures and early indicators of clinical efficacy. The trial incorporates protocol-defined stopping rules, centralized safety monitoring and oversight by an independent Data Safety Monitoring Board.
