4D Molecular Therapeutics (4DMT), the California-based biotechnology company focused on developing gene therapies for rare and cardiovascular, pulmonary, and ophthalmic diseases, has recently been issued a clinical hold by the FDA for its Fabry Disease (FD) gene therapy program (4D-310).  4DMT and Sangam Therapeutics are the leading developers in the Fabry disease space, and with the FDA’s clinical hold, the future of 4DMT’s program remains uncertain. As a result, Sangamo is expected to gain a significant market share, as its therapy will likely achieve approval before 4DMT’s therapy, says GlobalData, a leading data and analytics company.

4DMT paused the enrolment of patients to two of its trials for 4D-310 in January 2023, following significant adverse events where three patients experienced kidney issues; however, these were treated and resolved in a four-week period.

Akash Patel, Pharma Analyst at GlobalData, comments: “The 4DMT trial, however, presents challenges and barriers to the development of gene therapy as significant adverse events are still occurring in late-stage therapies, and this may present a deterrent for the development of further gene therapies in the long-term. This setback for 4DMT, although downplayed by the company in the short-term, will likely lead to Sangamo’s therapy becoming the lead FD gene therapy in the pipeline.”

4DMT is creating a gene therapy using an adeno-associated viral vector (AAV) and there is currently competition from several early-stage therapies in trial, such as Sangamo’ AAV-based Fabry gene therapy that is progressing to Phase III.

Patel concludes: “FD will likely become a disease that is treatable with gene therapy; however, barriers to access remain with late-stage trials to be completed, followed by likely issues surrounding pricing, insurance coverage, and reimbursement across the major markets in the US and Europe.”