Saol International Development Limited – FDA CRL

The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) to Saol International Development Limited (Saol Therapeutics Inc) regarding New Drug Application (NDA) 218679 for sodium dichloroacetate (DCA), intended for treating pyruvate dehydrogenase complex deficiency (PDCD). The primary reason for the denial was the failure to demonstrate substantial evidence of effectiveness. Two pivotal trials, SL1009-01 and SL1009-02, were deemed insufficient. SL1009-01, a randomized, double-blind, placebo-controlled trial, did not show statistically significant benefit on its primary endpoint, and secondary findings were not considered clinically meaningful or supported as surrogate endpoints. SL1009-02, which compared survival against an external control, was compromised by significant differences between the treated and control groups, including issues with disease onset ascertainment, baseline patient characteristics, diagnostic methodologies, and temporal bias.

Additional approvability issues identified included the lack of a thorough QT/QTc study to assess DCA's effect on QT interval prolongation, and the absence of a clinical trial evaluating the effect of food on DCA pharmacokinetics. The FDA requires the company to submit results from at least one new, adequate, and well-controlled clinical trial demonstrating effectiveness on clinically meaningful endpoints. Furthermore, Saol must conduct the specified pharmacology studies and provide a comprehensive safety update to address the deficiencies.