SL1009

The sponsor estimates that PDCD affects fewer than 1,000 individuals in the United States, with an incidence of approximately 1 in 40,000 live births. In a natural-history cohort of 59 participants, 23 (39%) had died; reported causes included severe lactic acidosis, respiratory failure, and infection. A separate neurodevelopmental study reported intellectual disability in 33 of 42 participants (79%) and significant adaptive-functioning impairment in 31 of 35 (89%). These estimates describe different populations and should not be treated as interchangeable measures of prognosis.

The pivotal SL1009-01 trial enrolled 34 participants. The original observer-reported primary efficacy endpoint was not met. The FDA reported a treatment difference of 0.29, with a 95% confidence interval of -0.62 to 1.21 and p=0.52, favoring placebo. Conference evidence reported reduced plasma lactate with DCA (p=0.006), while the sponsor reported motor improvement during longer treatment, including the open-label extension (p=0.002). These findings do not establish success on the prespecified primary endpoint. The sponsor reported gastrointestinal disorders in 2 participants (5.9%). Reversible peripheral neuropathy is a clinically limiting toxicity of chronic DCA exposure.

SL1009 remains investigational. The FDA found the original application insufficient to establish effectiveness and rejected the proposed external-control survival comparison as a basis for assessing treatment effect. The sponsor subsequently reported resubmission on June 30, 2026, acceptance as a complete Class 2 response, and a target FDA action date of December 30, 2026. Acceptance for review is not approval. Ketogenic dietary therapy remains a recommended treatment for primary PDCD; the evidence in this report does not establish that SL1009 should replace it.