FDA Issues Complete Response Letter for SL1009 for Pyruvate Dehydrogenase Complex Deficiency

In recent news, the FDA has issued Saol Therapeutics a complete response letter (CRL) for its investigational product SL1009 or sodium dichloroacetate oral solution (DCA) for the treatment of pyruvate dehydrogenase complex deficiency (PDCD), a rare mitochondrial metabolic disorder.¹

PDCD, caused by mutations in 1 of the components of the pyruvate dehydrogenase complex, affects fewer than 1000 individuals in the United States, with an incidence estimated at 1 in 40,000 live births. Neurological manifestations of the disorder include hypotonia, developmental delay, seizures, ataxia, and sometimes structural brain abnormalities visible on imaging, like brain atrophy or abnormal white matter. Some patients present at infancy, while others may have attenuated forms that survive into childhood or adulthood.

SL1009, a formulation of DCA, is an oral solution intended to be used in conjunction with a proprietary genetic test that helps determine appropriate dosing. In the CRL, the agency outlined specific issues that Saol must resolve to define the path forward, though none were related to SL1009’s manufacturing. The company noted that meeting these requirements will likely take several years and demand substantial financial investment.

"Families living with PDCD face an urgent and life-threatening unmet need," Dave Penake, chief executive officer at Saol, said in a statement.¹ "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."

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The new drug application (NDA), submitted in December 2024, was based on results from a phase 3, double-blind, placebo-controlled, crossover study (SL1009-01; NCT02616484) and a survival study (SL1009-02). In the phase 3 study, the Observer Reported Outcome survey's primary end point did not demonstrate statistical significance in the double-blind portion. However, longer duration of the therapy, including the open-label extension, demonstrated a statistically significant improvement in motor function among those in the intent-to-treat (ITT) population (P = .002).^2,3

Key findings from the phase 3 study, presented in June 2025 at the United Mitochondrial Disease Foundation Mitochondrial Medicine Conference in St. Louis, Missouri, showed that DCA was well tolerated, even upon chronic administration over 3 years. During that time, the most commonly reported adverse reaction, found in more than 5% of treated patients, was gastrointestinal disorders (n = 2; 5.9%). Additional data showed that DCA treatment significantly (P = .006) decreased plasma lactate concentrations while improving survival (P = .027) compared with appropriately matched controls.

To date, SL1009 has received priority review, orphan drug designation, and rare pediatric disease designation. Following the CRL, Saol reaffirmed that access to the agent will continue without interruption through both the ongoing open-label extension of the trial (NCT02616484) and the expanded access program (NCT06931262), which also includes emergency support for neonates with life-threatening lactic acidosis due to inborn errors of metabolism.¹

REFERENCES
1. Saol Therapeutics receives complete response letter from FDA for SL1009 (DCA) for the treatment of pyruvate dehydrogenase complex deficiency (PDCD). News release. Saol Therapeutics. September 8, 2025. https://www.prnewswire.com/news-releases/saol-therapeutics-receives-complete-response-letter-from-fda-for-sl1009-dca-for-the-treatment-of-pyruvate-dehydrogenase-complex-deficiency-pdcd-302548522.html
2. Saol Therapeutics announces submission of new drug application (NDA) to the U.S. FDA for SL1009. News release. Saol Therapeutics. December 3, 2025. https://saolrx.com/saol-therapeutics-announces-submission-of-new-drug-application-nda-to-the-u-s-fda-for-sl1009/
3. Saol Therapeutics announces poster presentation at the UMDF Mitochondrial Medicine 2025 Conference. News release. June 19, 2025. https://saolrx.com/saol-therapeutics-announces-poster-presentation-at-the-umdf-mitochondrial-medicine-2025-conference/