Saol Therapeutics announced that the U.S. Food and Drug Administration (FDA) has accepted its New Drug Application (NDA) for SL1009, a sodium dichloroacetate oral solution (DCA), for the treatment of Pyruvate Dehydrogenase Complex Deficiency (PDCD). The FDA has granted Priority Review to the NDA, setting a PDUFA goal date of May 27, 2025.
This decision underscores the potential of SL1009 to address a critical gap in the treatment of PDCD, a rare and life-threatening mitochondrial disorder primarily affecting the nervous system and skeletal muscle. Priority Review is reserved for drugs that, if approved, would significantly improve the safety or effectiveness of treatment for serious conditions.
Addressing a Critical Unmet Need in PDCD
PDCD is characterized by impaired carbohydrate oxidation, leading to decreased ATP production and energy failure. It is estimated that 300-500 patients are treated in expert centers in the US, with an overall prevalence thought to be as high as 2,000. Currently, there are no FDA-approved therapies for PDCD, leaving a significant unmet need for these patients.
"This NDA acceptance brings us one step closer to addressing the critical health challenges faced by these children and their families, where no approved treatment is currently available," said Dave Penake, Chief Executive Officer of Saol Therapeutics.
Mechanism of Action and Genetic Testing
SL1009 (DCA) works by inhibiting Pyruvate Dehydrogenase Kinase (PDK), which in turn stimulates residual Pyruvate Dehydrogenase Complex (PDC) activity, increasing energy (ATP) production by mitochondria. The therapy is designed to be used in conjunction with a proprietary genetic test that identifies each patient’s GSTZ1 genotype, allowing for individualized dosing to minimize adverse events such as peripheral neuropathy.
Clinical Trial Data Supporting NDA
The NDA is supported by data from a Phase 3 double-blind, placebo-controlled, cross-over study (SL1009-01) and a survival study (SL1009-02). The submitted evidence includes mechanistic characterization, along with nonclinical and clinical data demonstrating the safety and 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.
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.
Regulatory Designations
SL1009 has been granted Orphan Drug, Fast Track, and Rare Pediatric Disease Designations by the FDA. The Rare Pediatric Disease Designation makes SL1009 eligible for a Priority Review Voucher (PRV) upon approval.
Potential Impact
If approved, SL1009 would represent the first FDA-approved medication for PDCD, offering a targeted therapy to improve energy production in patients with this debilitating mitochondrial disorder. The use of a proprietary genetic test to guide dosing could also help to minimize potential side effects and optimize treatment outcomes.
