SL1009 resubmitted to FDA for pyruvate dehydrogenase complex deficiency

Children with pyruvate dehydrogenase complex deficiency (PDCD), a life-threatening mitochondrial disorder without an FDA-approved therapy, may soon have a renewed regulatory review option after Saol Therapeutics resubmitted its New Drug Application (NDA) for SL1009, sodium dichloroacetate (DCA), to the FDA.¹

“We are encouraged by the clarity and alignment achieved with the FDA during our recent interactions,” Dave Penake, chief executive officer of Saol Therapeutics, said in the company announcement. “This resubmission reflects the totality of evidence supporting SL1009.”

The resubmission follows an August 2025 Complete Response Letter (CRL), which, according to Saol, did not cite safety or manufacturing concerns but requested additional evidence to support approval. The company reported that subsequent FDA discussions included a Type A meeting in December and a Type C meeting in March, during which the agency recommended additional survival analyses. Saol stated that these analyses allowed the company to resubmit the NDA without conducting another clinical trial.

SL1009 remains investigational. If the FDA accepts the resubmission for review, the agency will assign a new Prescription Drug User Fee Act action date. Saol also reported that SL1009 has received Priority Review, Orphan Drug Designation, and Rare Pediatric Disease Designation. The company said it anticipates a Priority Review Voucher if the product is approved under the rare pediatric disease program.

PDCD is caused by impaired activity of the pyruvate dehydrogenase complex, which links glycolysis to mitochondrial oxidative metabolism. The resulting energy deficit can lead to lactic acidosis, neurologic impairment, developmental delay, seizures, hypotonia, and early mortality. In a cohort describing 371 patients with PDCD, investigators reported broad clinical heterogeneity, with disease severity influenced by biochemical phenotype and underlying genetic cause.² Current management is largely supportive and may include dietary and metabolic strategies, seizure management, rehabilitation services, and treatment of complications. The absence of an approved disease-targeted therapy remains a major limitation for clinicians and families.

DCA is intended to increase activity of the pyruvate dehydrogenase complex by inhibiting pyruvate dehydrogenase kinase, thereby promoting the active form of the enzyme and potentially reducing lactate accumulation. An earlier controlled study of DCA in children with congenital lactic acidosis demonstrated biochemical effects on lactate but did not establish broad clinical efficacy across a heterogeneous pediatric population.³ Safety considerations have also been important in the DCA development history; in a randomized study in adults with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes, DCA was associated with toxic neuropathy, underscoring the need for careful dosing and monitoring.⁴

Saol’s current NDA is tied to a proprietary dose-determining genetic test. The company stated that, in collaboration with Medosome Biotec, it filed a Humanitarian Device Exemption application for the test, which would serve as a required companion diagnostic for patients treated with SL1009.^` The press release did not provide newly reported numerical efficacy results, details of the additional survival analyses, or subgroup findings from the cited phase 3 and long-term open-label extension data.

For pediatric clinicians, the central question is whether the FDA will consider the totality of existing evidence sufficient in a disease with substantial unmet need and limited feasibility for large trials. The regulatory path may be particularly relevant for ultra-rare mitochondrial disorders, where natural history, genotype, functional status, and survival outcomes can be difficult to interpret without large controlled datasets.

The next step is FDA acceptance of the resubmitted NDA and assignment of an action date. Until then, SL1009 should be viewed as an investigational therapy, and the clinical applicability of the submitted analyses remains uncertain pending FDA review and public availability of the underlying data.

References

1. Saol Therapeutics. Saol Therapeutics resubmits the New Drug Application for SL1009 (DCA) for the treatment of pyruvate dehydrogenase complex deficiency (PDCD), an ultra-rare disease. PRNewswire. July 6, 2026. Accessed July 8, 2026. https://www.prnewswire.com/news-releases/saol-therapeutics-resubmits-the-new-drug-application-for-sl1009-dca-for-the-treatment-of-pyruvate-dehydrogenase-complex-deficiency-pdcd-an-ultra-rare-disease-302816217.html

2. Patel KP, O’Brien TW, Subramony SH, Shuster J, Stacpoole PW. The spectrum of pyruvate dehydrogenase complex deficiency: clinical, biochemical and genetic features in 371 patients. Mol Genet Metab. 2012;105(1):34-43. doi:10.1016/j.ymgme.2011.09.032

3. Stacpoole PW, Kerr DS, Barnes C, et al. Controlled clinical trial of dichloroacetate for treatment of congenital lactic acidosis in children. Pediatrics. 2006;117(5):1519-1531. doi:10.1542/peds.2005-1226

4. Kaufmann P, Engelstad K, Wei Y, et al. Dichloroacetate causes toxic neuropathy in MELAS: a randomized, controlled clinical trial. Neurology. 2006;66(3):324-330. doi:10.1212/01.wnl.0000196641.05913.27