FDA Rejects Saol’s PDCD Therapy as Company Seeks Path to Approval without Additional Trial

Rare Daily Staff

The U.S. Food and Drug Administration notified Saol Therapeutics that it would not approve the company’s experimental therapy, SL1009, for the ultra-rare and life-threatening mitochondrial disease pyruvate dehydrogenase complex disease.

The FDA provided specific observations in the letter notifying the company it would not approve SL1009, which Saol will need to address to clarify the path forward. These observations did not include any findings regarding the manufacturing of SL1009. Addressing the deficiencies as the FDA requested would take several years and require significant financial resources. The company is hoping to avoid the need for an additional clinical trial.

The rejection comes as the agency recently unveiled principles acknowledging the challenges of demonstrating the effectiveness of therapies for ultra-rare disease populations and its willingness to consider additional supportive data.

Pyruvate dehydrogenase complex deficiency (PDCD) is a rare and life-threatening genetic disorder that can cause a chronic energy deficit, leading to lactic acidosis, profound developmental problems, and early childhood death. There are currently no FDA-approved therapies for PDCD. The condition affects about 90 newborns annually.

SL1009 (sodium dichloroacetate oral solution) is an experimental product that, if approved, would be used with a proprietary dose-determining genetic test to treat an orphan pediatric-onset mitochondrial disease. SL1009 has received Priority Review, Orphan Drug, and Rare Pediatric Disease designations. Saol, in collaboration with Medosome Biotec, also filed a Humanitarian Device Exemption application for the dose-determining genetic test, which would serve as a required companion diagnostic for patients treated with SL1009.

Saol said it remains encouraged by the four years of clinical data captured through two phase 3 studies, a double-blind placebo-controlled trial that continues in an open-label extension, and a survival analysis compared with a natural history cohort. Saol said it believes SL1009, with its established safety profile, could be an important treatment option for patients with PDCD.

“Families living with PDCD face an urgent and life-threatening unmet need,” said Dave Penake, CEO of Saol Therapeutics. “We are encouraged by recent FDA actions and commentary that recognize the importance of regulatory flexibility and speed for treating rare diseases. Traditional clinical trials often take many years, time that children with PDCD simply do not have. We remain committed to productive conversations with the agency to identify a path forward that brings this therapy to patients as swiftly as possible.”

In the interim, Saol said access to SL1009 will continue without interruption through both the ongoing open-label extension of the clinical trial and the Expanded Access Program, which also includes emergency support for neonates with life-threatening lactic acidosis due to inborn errors of metabolism.