Saol Therapeutics submits NDA for SL1009 to treat Pyruvate Dehydrogenase Complex Deficiency

A New Drug Application SL1009, Sodium Dichloroacetate Oral Solution (DCA) for the treatment of Pyruvate Dehydrogenase Complex Deficiency (PDCD) has been submitted to the FDA, according to an announcement from Saol Therapeutics.¹

The treatment, which if approved, would potentially be the first approved medication for the mitochondrial disease, has been granted Orphan Drug, Rare Pediatric Disease, and Fast Track Designations by the federal agency.¹

PDCD is a disorder of carbohydrate oxidation that mostly affects the nervous system and skeletal muscle, leading to decreased ATP production and energy failure. In the United States, where there is currently no FDA-approved treatment for PDCD, the disease impacts an estimated 300 to 500 patients that are treated in expert centers throughout the country, according to Saol Therapeutics. Overall, the prevalence is estimated to be as high as 2000.¹

PDCD is the most common form of congenital lactic acidosis, a life-threatening condition that can occur as early as the neonatal period. Patients can experiences signs and symptoms—that usually begin soon after birth but could appear later in childhood—consisting of extreme tiredness, poor feeding, rapid breathing, and other signs of neurological and neuromuscular dysfunction such as developmental delay, low muscle tone, abnormal eye movements and seizures, stated Saol in the announcement.¹

"The NDA submission is a tremendous milestone and the culmination of years of effort," said Peter Stacpoole, MD, inital study sponsor of SL1009-01, in a statement. "I am grateful for the clinicians and families who participated in the trial."¹

Supporting the NDA submission were results from a phase 3 double-blind, placebo-controlled, cross-over study (SL1009-01; NCT02616484) and a survival study (SL1009-02).^1,2

According to Saol, the totality of evidence submitted in the NDA includes mechanistic characterization, nonclinical and clinical safety and efficacy evidence to support the clinical benefit of DCA in PDCD patients.¹

In SL1009-01, the primary outcome was a daily Observer Reported Outcomes survey tool to measure changes in motor domains, along with the safety and tolerability of SL1009 compared to placebo. A key secondary outcome was the reduction in plasma lactate of SL1009 compared to placebo.¹

Those receiving treatment were dose-stratified post-randomization using a proprietary genetic test that identified each patient's GSTZ1 genotype. This provided an individualized dose intended to reduce adverse events.¹

The survival study compared outcomes for SL1009-treated patients in the phase 3 study with external, untreated natural history patients with PDCD. According to the company, detailed data is expected to be presented at an upcoming medical conference.¹

"This NDA submission is an important step in bringing this therapy to children living with PDCD in the US," said Dave Penake, CEO, Saol Therapeutics in the submission announcement.¹

"We look forward to continuing our ongoing discussions with the FDA as we move closer to addressing this significant unmet need of children suffering from PDCD," said Penake.¹

References:

1. Saol Therapeutics announces submission of New Drug Application (NDA) to the US FDA for SL1009. Saol therapeutics. Press release. December 3, 2024. Accessed December 3, 2024. https://prnmedia.prnewswire.com/news-releases/saol-therapeutics-announces-submission-of-new-drug-application-nda-to-the-us-fda-for-sl1009-302320045.html

2. Trial of Dichloroacetate in Pyruvate Dehydrogenase Complex Deficiency: (DCA/PDCD). ClinicalTrials.gov. Updated October 15, 2024. Accessed December 3, 2024. https://clinicaltrials.gov/study/NCT02616484