FDA decision delay for Applied Tx rare disease drug sends biotech's stock tumbling after hours

Even after a failed phase 3 pediatric clinical trial, Applied Therapeutics forged ahead with an FDA filing for potential market approval. Now the regulatory agency has extended the review period for the rare disease prospect, pushing back a possible decision date into November and sending the biotech’s stock tumbling.

The drug at question is govorestat, an aldose reductase inhibitor designed to treat classic galactosemia, an inherited metabolic disorder. In February, the FDA accepted the investigational drug for review, granting priority review, with a decision slated for Aug. 28. Now, the agency has moved that date back three months to Nov. 28, according to a March 28 release.

The FDA told Applied that more time was needed to examine supplemental analyses of already submitted data and determined that the additional info constitutes a major amendment to the new drug application, according to the release.

Applied shared news of the delay after market close on Thursday, sending the company’s stock down 14% after hours, dropping from $6.80 per share at close to $5.80 as of 7:57 p.m. ET, March 28.

“While the PDUFA action date extension represents a delay, we remain confident in the potential for govorestat approval for galactosemia and we will continue to work closely with the FDA throughout the review process,” Applied founder and CEO Shoshana Shendelman, Ph.D., said in the release. “During this time, we are committed to maintaining the expanded access program for govorestat to ensure patients with galactosemia have the opportunity to receive this important treatment.”

Last April, the biotech shared phase 3 results assessing the asset, which is the company’s lead pipeline program. The study found that govorestat was no better than placebo at improving a composite of four measures—including language skills, self-care capabilities and more—among children with galactosemia.  

Despite the failure, the New York-based biotech argued that the data show “consistent and sustained clinical benefit on activities of daily living, behavioral symptoms, cognition, adaptive behavior and tremor,” and filed a new drug application with the FDA.

Initially, Applied had planned to ask for U.S. approval 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. The phase 3 trial gave Applied evidence of the effect of govorestat, also known as AT-007, on clinical outcomes.  

This isn’t the first of the company’s troubles with the drug. Back in August 2020, the FDA placed a partial clinical hold on the late-stage govorestat program, requesting more technical information to ensure patients had "access to the prospect of direct benefit of the drug."

If approved, govorestat would become the first medication for treating galactosemia. The candidate has snagged orphan drug designation, fast track status and pediatric rare disease designation from the FDA in the indication. 

Applied is also assessing govorestat as a potential treatment for two other rare neurological diseases: SORD Deficiency and PMM2-CDG.