Advocacy Groups, Scientists Urge FDA to Approve Therapy for Ultra-Rare Mitochondrial Disease

Rare Daily Staff

More than 80 scientists, doctors, and advocacy organizations have called on U.S. Food and Drug Administration Commissioner Martyin Makary allow an expedited, flexible review of Saol Therapeutics’ experimental drug for pyruvate dehydrogenase complex deficiency, an ultra-rare mitochondrial disorder.

The plea follows the FDA’s decision in September to reject Saol’s application for SL1900, a sodium dichloroacetate (DCA) oral solution. While the agency did not cite manufacturing issues, it required additional data that the company said would necessitate years of work and significant financial investment. Saol has sought to avoid the need for another clinical trial.

Patient advocacy groups—including the United Mitochondrial Disease Foundation, MitoAction, Cure Mito Foundation, Hope for PDCD, and the Elizabeth Watt PDCD Research Fund—joined the request. In a joint letter, signatories urged the FDA to use regulatory flexibility, arguing that DCA has shown decades of safe use in research and practice for mitochondrial diseases, with only rare reversible peripheral neuropathy effectively mitigated by modern dosing techniques.

The letter stated that DCA has led to sustained developmental improvements and reduced mortality in children with PDCD compared with historical cohorts. Without regulatory relief, they warned, approval could be financially out of reach for Saol, rendering DCA inaccessible for families. Advocates argue that further randomized controlled clinical trials are not feasible, given the small patient population and limited resources. They are urging the FDA to grant full or accelerated approval for DCA based on existing evidence and the needs of affected patients.

“This will result in unnecessary deaths, irreversible developmental decline, and health complications for these vulnerable children,” the organizations wrote.

PDCD is a rare genetic disorder that disrupts carbohydrate metabolism and is the most common cause of congenital lactic acidosis. The condition often triggers developmental delays, epilepsy, neurological decline, and, in many cases, early death.

“Every day without access to DCA is a day when preventable harm may be occurring,” said Dr. Rebecca Ganetzky, a pediatrician, biochemical geneticist, and co-author of the letter. “The FDA has the authority to apply flexibility for ultra-rare diseases like PDCD, where the clinical benefit is clear and the consequences of delay are devastating.”

Photo: Martin Makary, U.S. Food and Drug Administration Commissioner