The US Food and Drug Administration (FDA) has declined to approve Applied Therapeutics’ govorestat for classic galactosemia, prolonging the wait for the first marketed treatment for the genetic disease.
US-based Applied Therapeutics had been hoping its central nervous system (CNS)-penetrant aldose reductase inhibitor (ARI) would become the first pharmacological treatment for the disease. The FDA’s complete response letter (CRL) cited deficiencies in Applied Therapeutics’ new drug application (NDA), as per a 27 November press release.
Shares in the Nasdaq-listed company sank 76% in after-hours trading following the announcement. Applied Therapeutics has a market cap of $997.1m.
The FDA had previously requested extra time to decide on the drug earlier this year after extra data was submitted by Applied Therapeutics.
The biopharma company said it is now reviewing feedback from the agency and plans to immediately meet with the FDA to discuss resubmitting the NDA or appealing the decision for its drug.
There are around 3,300 patients in the US with galactosemia, an inherited metabolic disorder that affects the body’s ability to properly convert galactose to glucose. A deficiency in the enzyme galactose-1-phosphate uridylyl transferase (GALT) causes a buildup of galactose, leading to an improper conversion to the toxic metabolite galactitol.
Accumulation of this molecule causes neurological complications, including deficiencies in cognition, behaviour, and motor skills, as well as tremors. The only current treatment is the avoidance of galactose or lactose in diets, including those of newborns such as breast milk.
Applied Therapeutics points to the “rapid and sustained reductions in galactitol” produced by the govorestat in paediatric clinical trials. In the Phase III registrational ACTION-Galactosemia Kids study (NCT04902781) in children with galactosemia between the ages of two and 17, govorestat led to improvements in activities of daily living, behavioural symptoms, cognition, fine motor skills and tremors.
Applied Therapeutics’ CEO Shoshana Shendelman said: “We are disappointed by the FDA’s decision today, […] govorestat has the potential to change the lives of patients with galactosemia, which we believe is evidenced by the breadth of efficacy and safety data demonstrating its ability to stop the decline on progressive clinical outcomes.
“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.”
Nicole Casale, president of the Galactosemia Foundation, stated: “The galactosemia community is devastated by the FDA's decision to not approve the first and currently only potential treatment for this ultra-rare, life-altering disease.
“Individuals facing this devastating disease need a treatment now. We urge the FDA to reconsider their decision on behalf of those facing this disease, their family members who love and care for them, and future generations who may be impacted by this genetic condition.”
Govorestat has a wealth of FDA tags designed to expedite market access, including orphan drug, paediatric rare disease, and fast track designations. The drug is also currently under review by the European Medicines Agency (EMA), where it holds orphan medicinal product designation.
