ROSWELL, Ga. and DUBLIN and HAMILTON, Bermuda, Dec. 3, 2024 /PRNewswire/ — Saol Therapeutics, a privately held, clinical-stage pharmaceutical company, today announced the submission of a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for approval of SL1009, Sodium Dichloroacetate Oral Solution (DCA) for use with a proprietary genetic test, for the treatment of an orphan pediatric mitochondrial disease, Pyruvate Dehydrogenase Complex Deficiency (PDCD)1. SL1009 has been granted Orphan Drug, Fast Track and Rare Pediatric Disease Designations by the FDA and is thus eligible for Priority Review and a Priority Review Voucher.
The NDA is supported by results from the Phase 3 double-blind placebo controlled cross-over study (SL1009-01) and a survival study (SL1009-02). 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.
The primary endpoint of SL1009-01 was a daily Observer Reported Outcomes survey tool to measure changes in motor domains (ObsROmotor) as well as the safety and tolerability of SL1009 compared to placebo. A key secondary endpoint measured the reduction in plasma lactate of SL1009 compared to placebo. Patients receiving DCA were dose-stratified post-randomization utilizing a proprietary genetic test. The test identifies each patient’s GSTZ1 genotype to provide individualized dosing intended to reduce adverse events, such as peripheral neuropathy.
A second study, SL1009-02, was a survival analysis that compared outcomes for DCA-treated patients in the Phase III study with external, untreated natural history cohort of patients with PDCD. Patients were matched on age and sex.
Peter Stacpoole, MD, initial study sponsor of SL1009-01 said “The NDA submission is a tremendous milestone and the culmination of years of effort. I am grateful for the clinicians and families who participated in the trial.”
Detailed data is expected to be presented at an upcoming medical conference.
DCA is not currently approved for any indication in the United States.
About SL1009 (DCA) and GSTZ1/MAAI Proprietary Genetic Test
SL1009, if approved by the FDA after a review of safety and efficacy, has the potential to be the 1st approved medication for the mitochondrial disease PDCD and would be available as an oral solution. Gene mutations in the mitochondrial Pyruvate Dehydrogenase Complex (PDC) lead to congenital PDCD. PDC is inhibited by pyruvate dehydrogenase kinases (PDK), that may be over-expressed in PDCD. DCA inhibits PDK to stimulate residual PDC activity and increase energy (ATP) production by mitochondria. Dosing is based on a proprietary genetic test that dichotomizes subjects into “fast” and “slow” drug metabolizers, providing individualized dosing.
About Pyruvate Dehydrogenase Complex Deficiency (PDCD)
PDCD is a mitochondrial disorder of carbohydrate oxidation that mostly affects the nervous system and skeletal muscle and leads to decreased ATP production and energy failure. It is estimated that 300-500 patients are treated in expert centers in the US, and the overall prevalence is thought to be as high as 2,000. PDCD is the most common cause of congenital lactic acidosis, a life-threatening condition that may occur as early as the neonatal period. Patients suffering from PDCD may also exhibit extreme tiredness (lethargy), poor feeding, rapid breathing (tachypnea), and other signs of neurological and neuromuscular dysfunction such as developmental delay, low muscle tone (hypotonia), abnormal eye movements and seizures. Signs and symptoms usually begin soon after birth but may appear later in childhood2.
There are currently no FDA-approved therapies for PDCD.
About Saol Therapeutics
Saol Therapeutics (pronounced “Sail”) is a privately held, clinical-stage, pharmaceutical company with operations in Roswell, GA, Dublin, Ireland and Hamilton, Bermuda. Saol is focused on development activity in CNS disorders such as spasticity and pain management, and orphan diseases. Saol is committed to providing and advancing therapeutic options for patients and the physicians treating these populations. For more information, visit www.saolrx.com.
References
- 1. https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=45290, Accessed October 2024
- 2. Ganetzky R, McCormick EM, Falk MJ. Primary Pyruvate Dehydrogenase Complex Deficiency Overview. 2021 Jun 17. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2023. PMID: 34138529.