FDA Accepts SL1009 Resubmission for PDCD, Sets December PDUFA Date

The FDA has acknowledged Saol Therapeutics' resubmission of its New Drug Application (NDA) for SL1009 (sodium dichloroacetate, DCA) for pyruvate dehydrogenase complex deficiency (PDCD), classifying it as a complete, Class 2 response and setting a new PDUFA target action date of December 30, 2026.¹ PDCD is a rare, life-threatening mitochondrial disorder with no FDA-approved therapies.

Path to resubmission

The original NDA was submitted in December 2024, supported by results from the phase 3, double-blind, placebo-controlled, crossover SL1009-01 trial (NCT02616484) and a companion survival study, SL1009-02, that compared DCA-treated patients with an age- and sex-matched external natural history cohort.² SL1009-01's primary endpoint, a daily Observer Reported Outcomes survey measuring motor function (ObsROmotor), did not reach statistical significance during the double-blind portion; longer treatment duration, including the trial's open-label extension, was associated with a statistically significant improvement in motor function in the intent-to-treat population (P = .002).³

In the study, DCA treatment also significantly reduced plasma lactate concentrations (P = .006) and was associated with improved survival relative to matched controls (P = .027).³ Peter Stacpoole, MD, the trial's initial study sponsor, called the original NDA submission "a tremendous milestone and the culmination of years of effort.”²

The FDA issued a complete response letter (CRL) in August 2025 that did not raise concerns related to SL1009's safety profile or manufacturing but requested additional evidence to support approval.^1,4 Following a Type A meeting in December 2025 and a Type C meeting in March 2026, the FDA advised Saol to conduct additional survival analyses; the company said this guidance allowed it to proceed directly to resubmission, filed on June 30, 2026, without an additional clinical trial.^1,5

“Having a confirmed action date matters greatly to the families of children living with PDCD, who have waited a long time for a potential treatment option,” Dave Penake, chief executive officer of Saol Therapeutics, said in a statement.¹ “We remain confident in the totality of evidence behind SL1009 and what it can mean for these patients.”

About SL1009 and PDCD

SL1009 is an oral formulation of DCA intended for use alongside a proprietary genetic test that identifies each patient's GSTZ1 genotype to guide individualized dosing and reduce adverse events such as peripheral neuropathy.^2,3 Mechanistically, DCA inhibits pyruvate dehydrogenase kinase, an enzyme often overexpressed in PDCD, to stimulate residual activity of the pyruvate dehydrogenase complex and increase mitochondrial energy production.

PDCD is caused by mutations affecting components of that complex and is estimated to affect fewer than 1,000 people in the US, with an incidence of about 1 in 40,000 live births; neurological manifestations include hypotonia, developmental delay, seizures, ataxia, and structural brain abnormalities, and the disorder is the most common cause of congenital lactic acidosis.^4,6

SL1009 has received Priority Review, Orphan Drug, and Rare Pediatric Disease designations, and Saol anticipates qualifying for a Priority Review Voucher upon approval.¹ Patients can currently access DCA through SL1009-01's ongoing open-label extension or through an expanded access program (NCT06931262) that includes emergency support for neonates with life-threatening lactic acidosis due to inborn errors of metabolism.⁴

REFERENCES
1. Saol Therapeutics Announces the Acceptance of Resubmission of SL1009 (DCA) by the FDA with PDUFA Date of Dec. 30, 2026. News release. Saol Therapeutics. July 28, 2026. Accessed July 31, 2026. https://www.prnewswire.com/news-releases/saol-therapeutics-announces-the-acceptance-of-resubmission-of-sl1009-dca-by-the-fda-with-pdufa-date-of-dec-30-2026-302836586.html
2. Saol Therapeutics Announces Submission of New Drug Application (NDA) to the U.S. FDA for SL1009. News release. Saol Therapeutics. December 3, 2024. Accessed July 31, 2026. 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. Saol Therapeutics. June 19, 2025. Accessed July 31, 2026. https://saolrx.com/saol-therapeutics-announces-poster-presentation-at-the-umdf-mitochondrial-medicine-2025-conference/
4. 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. Accessed July 31, 2026. 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
5. Saol Therapeutics Resubmits the New Drug Application for SL1009 (DCA) for the Treatment of Pyruvate Dehydrogenase Complex Deficiency (PDCD), an Ultra-Rare Disease. News release. Saol Therapeutics. July 7, 2026. Accessed July 31, 2026. https://saolrx.com/saol-therapeutics-resubmits-the-new-drug-application-for-sl1009-dca-for-the-treatment-of-pyruvate-dehydrogenase-complex-deficiency-pdcd-an-ultra-rare-disease/
6. Ganetzky R, McCormick EM, Falk MJ. Primary Pyruvate Dehydrogenase Complex Deficiency Overview. In: Adam MP, Feldman J, Mirzaa GM, et al., eds. GeneReviews. Seattle, WA: University of Washington, Seattle; 1993-2023. Updated June 17, 2021. PMID: 34138529.