Applied Therapeutics fails phase 3 rare disease trial but plans to seek approval anyway

Applied Therapeutics’ phase 3 pediatric rare disease clinical trial has failed. But the biotech, which buried that news more than 500 words into its press release, framed the study as positive and outlined plans to meet with the FDA to discuss a filing for approval.

New York-based Applied ran the phase 3 study to show whether its aldose reductase inhibitor is better than placebo at improving symptoms in children with galactosemia, a rare disease that can cause developmental delays, speech problems and motor function abnormalities. The primary endpoint was a composite of four measures that looked at language skills, self-care capabilities and more. 

Govorestat was no better than placebo at improving those symptoms, causing the clinical trial to miss its primary endpoint. Or, as Applied eventually put it, “statistical significance defined as a p value of <0.05 was not met on the primary endpoint.”

Applied brushed over the failure, arguing the data show “consistent and sustained clinical benefit on activities of daily living, behavioral symptoms, cognition, adaptive behavior and tremor.” To make the case for govorestat, the biotech pointed to “systematic improvement over time” for the overall primary endpoint and “for a pre-specified sensitivity analyses including cognition.” The respective p-values were 0.1030 and 0.0698, respectively. 

Applied also highlighted a post hoc analysis of the primary endpoint that excluded two of the four measures, namely the ones that looked at speech and language. Removing half of the measures and focusing on behavior and activities of daily living resulted in a post hoc p-value of 0.0205. The biotech said the benefit “strengthened over time.” Tests of the effect of govorestat on tremor and adaptive skills yielded p values of 0.0428 and 0.0265, respectively.

Based on the data, Applied plans to meet with the FDA as soon as possible to discuss a potential filing for approval in the second half of 2023. A filing for approval in Europe is scheduled for mid-2023. Applied had planned to file for approval in the U.S. on the strength of biomarker data, only for the FDA to say it would likely need evidence the drug candidate improves clinical outcomes to receive a positive decision.

Applied now has evidence of the effect of govorestat, also known as AT-007, on clinical outcomes. What the FDA makes of it remains to be seen. In conjunction with the data drop, the biotech disclosed a $30 million private placement that it expects to fund operations through to the middle of next year.

Shares in Applied rose 18% in premarket trading to breach the $1 mark.