The Food and Drug Administration has rejected Applied Therapeutics’ application to approve its experimental treatment for classic galactosemia, a rare metabolic disorder the affects the body’s ability to process sugar.
News of the rejection, which came late Wednesday, sent Applied shares tumbling in Friday trading after the Thanksgiving holiday. The biotechnology company intends to review the FDA’s feedback and request a meeting to discuss a potential resubmission of its application, or to appeal the agency’s complete response letter.
“We are disappointed by the FDA’s decision,” company CEO Shoshana Shendelman said in a statement. “As we move forward, we plan to work with the FDA to address the concerns in the CRL and determine an expeditious path to bring this much needed treatment to patients.”
Classic galactosemia is caused by mutations in genes that encode for enzymes responsible for breaking down galactose, a sugar that’s found in milk. Without this enzyme, galactose converts to a toxic substance that causes serious neurological complications, hinders development and can lead to liver failure or death if newborns with the disease are not put on a special diet.
According to Applied, about 3,300 people are thought to have the condition in the U.S., with approximately 80 to 100 new diagnoses each year.
“Galactosemia has a large impact on quality of life, and right now, there are no drugs approved to stop the worsening or improve outcomes, or really to do anything for patients with this terrible disease,” Shendelman told BioPharma Dive in an interview ahead of the FDA’s decision.
According to Applied, the FDA’s rejection letter cited “deficiencies” in the company’s application, which left analysts guessing about the agency’s reasons.
“Credibility damage will be tough to bounce back from following the FDA's Thanksgiving rejection in galactosemia, and lack of substantial detail around how the review went south,” wrote Brian Skorney, an analyst at Baird, in a note to clients last week.
Applied’s drug, called govorestat, inhibits the enzyme aldose reductase, which converts galactose into that toxic substance, galactitol.
The company evaluated the drug in a Phase 3 trial, results from which missed the study’s primary goal. But Applied had pointed to data showing signs of improvement as well as reductions in galactitol levels in children given govorestat.
“Even though [Applied’s] trial missed its primary endpoint, we thought the totality of the data might be appreciated due to the the high unmet need and patient advocacy efforts,” wrote Leerink Partners analyst Joseph Schwartz in a client note last week.
Shendelman said Applied plans to apply for approval of govorestat in another rare disease called SORD deficiency in the first quarter next year.
