RARE Daily

FDA Places Hold on 4D Molecular Gene Therapy for Fabry Disease

February 6, 2023

Rare Daily Staff

4D Molecular said the U.S. Food and Drug Administration placed a clinical hold on its experimental gene therapy for Fabry disease, a rare lysosomal storage disorder.

The company, in a filing with the U.S. Securities and Exchange Commission, said that when the FDA notified it of the clinical hold it directed it to continue long term follow up of treated patients already in the study. It is expected to provide feedback regarding the 4D-310 trials within 30 days.

The hold happened after 4D Molecular announced in January that it would enroll addition patients in the current 4D-310 clinical study for Fabry disease. The program will be evaluated in the second half of 2023 after 12-month clinical data are obtained on all six of the currently enrolled patients, including on-going safety and cardiac endpoints for a potential pivotal trial as recommended by the FDA.

The company reported three instances of atypical hemolytic uremic syndrome, a rare and life-threatening condition that causes blood clots to form in the kidneys and elsewhere.

The company said it reported improvements in all cardiac endpoints listed above in patients who reached 12 months follow up, and the single available cardiac biopsy was positive for widespread genome delivery and transgene expression from 4D-310.

Fabry disease is a genetic disorder of the GLA gene that results in the body’s inability to produce an enzyme called alpha-galactosidase or AGA, causing the accumulation of the substrate globotriaosylceramide in critical organs, including the heart, kidney, and blood vessels. Such substrate accumulation can lead to life-threatening hypertrophic cardiomyopathy, heart failure, arrhythmias, various degrees of kidney dysfunction and cerebrovascular stroke. Fabry disease progression results in increased morbidity, mortality, and cost of care.

4D-310 uses a proprietary and optimized AAV vector to deliver a functional copy of the GLA gene, resulting in AGA production in target tissues. The proprietary vector in 4D-310 is designed for efficient, low-dose, intravenous delivery to key affected tissues in Fabry disease, including cardiac tissue, kidney, and vascular smooth muscle tissues.

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