In a news release on the company’s website, biopharmaceutical company Applied Therapeutics, Inc. shared that positive data was available from the Phase 3 ACTION-Galactosemia Kids trial. Within the trial, researchers evaluated govorestat (AT-007) as a therapeutic option for children living with galactosemia. Govorestat is an investigational Aldose Reductase Inhibitor (ARI) that is able to cross the blood-brain barrier. Outside of galactosemia, govorestat is in development for SORD deficiency and Phosphomannomutase 2 deficiency (PMM2-CDG). It has received Orphan Drug designation in both the United States and European Union, as well as Pediatric Rare Disease (galactosemia, PMM2-CDG) and Fast Track (galactosemia) designations. 

Altogether, 47 children between two and 17 years old enrolled in the ACTION-Galactosemia Kids trial. Researchers evaluated the safety, efficacy, and tolerability of govorestat over time with follow-ups every six months. Findings from the study include:

• Though the trial did not reach statistical significance in its primary endpoint, it did suggest that govorestat improved cognition and behavior. 
• Govorestat treatment helped improve childrens’ abilities to perform daily tasks like feeding, dressing, and playing. The treatment also reduced tremors and benefited behavioral issues. 
• Children with severe speech deficits saw some improvement on govorestat compared to the group receiving a placebo. 
• Govorestat was safe and well-tolerated with no serious adverse reactions occurring. 
• Galactitol levels were reduced throughout the treatment process, preventing tissue damage.

Moving forward, Applied Therapeutics intends to request a meeting with the U.S. Food and Drug Administration to discuss the filing of a New Drug Application (NDA). Considering that there are no specific galactosemia treatments currently, govorestat has the potential to confer significant benefits to these patients. 

What is Galactosemia? 

Galactosemia is a rare hereditary disorder in which someone is unable to process galactose, a type of sugar that is found in milk (including mother’s milk). Normally, our bodies use an enzyme called galactose-1-phosphate uridylyltransferase (GALT) to transition galactose into glucose. People with galactosemia don’t have enough of the enzyme, or enough functional enzyme, to break down galactose. This is due to GALT, GALK1, or GALE mutations; these are responsible for galactosemia types I, II, and III respectively. Galactosemia type I is considered to be the most severe form. Symptoms typically appear within a few days or weeks following birth and may include:

• Failure to thrive
• Lethargy
• Jaundice (yellowing of the skin, eyes, and mucous membranes)
• Liver damage/disease
• Enlarged liver
• Abdominal ascites 
• Diarrhea
• Tissue wasting
• Extreme weight loss
• Delayed growth
• Feeding difficulties
• Abnormal bleeding

Complications of galactosemia, which may occur if infants are not placed on low-galactose diets, may include:

• Sepsis
• Intellectual disability
• Ovarian insufficiency
• Developmental delays
• Cataracts