NEW YORK – The US Food and Drug Administration has removed its clinical hold on 4D Molecular Therapeutics' Phase I/II INGLAXA trial of the investigational gene therapy 4D-310 in Fabry disease cardiomyopathy.
4DMT expects to resume enrollment in the clinical trial this year, the Emeryville, California-based biopharma company said when reporting Q2 2024 financial results last week.
Fabry disease is caused by mutations in the GLA gene that result in an inability to produce the enzyme AGA, which leads to accumulation of globotriaosylceramide in various organs, including the heart and kidneys. 4D-310 uses a cardiac-targeted C102 vector to deliver a functional copy of a GLA transgene that encodes for AGA.
However, in January 2023, 4DMT paused enrollment in clinical trials of 4D-310 after reporting three instances of atypical hemolytic uremic syndrome among the six patients who had received the gene therapy. The FDA then ordered a clinical hold on the Phase I/II trial in the US the following month.
4DMT late last year said it had reached an agreement with the FDA on a plan to lift the hold on the clinical trial, which included a nonhuman primate study to evaluate the safety and biodistribution of intravenous 4D-310 with a new immunosuppressive regimen and expected to submit these results to the FDA in the second quarter of 2024.
Earlier this year, 4DMT said five patients who had previously received the gene therapy with at least a year of follow-up data improved on cardiac endpoints, including peak VO2 and cardiac quality of life, and that cardiac biopsies from one patient at weeks six and 24 showed durable transgene expression and clearance of globotriaosylceramide substrate in cardiomyocytes.
There were no new treatment-related adverse events higher than grade 1, and the three cases of atypical hemolytic uremic syndrome fully resolved.
4DMT said it expects to resume enrollment in the Phase I/II trial this year and will share additional program updates in 2025.
4DMT had $578 million in cash and cash equivalents as of June 30, which the company expects will fund operations into the first half of 2027. The company reported a net loss of $35 million in Q2 2024, or $.63 per share, compared to a net loss of $29.6 million during the same period last year, or $.77 per share.