Within the Phase 3 APHENITY study, researchers worked to determine the efficacy of sepiapterin in both adults and children with phenylketonuria (PKU). Formerly known as PTC923, sepiapterin was developed by global biopharmaceutical company PTC Therapeutics, whose mission is to develop innovative therapies within the rare disease space. It is an orally administered synthetic sepiapterin formulation. Sepiapterin is a precursor to intracellular tetrahydrobiopterin. Since phenylketonuria is an inborn error of metabolism, sepiapterin could potentially change the treatment landscape.
In a news release from PTC Therapeutics, the company shared that the primary endpoint had been met within the study. Altogther, 156 people with PKU enrolled. In the first two weeks, all patients were given sepiapterin. These patients were then split into two groups, one of which was given the placebo and the other of which continued on sepiapterin. When the trial moved to that second phase, 98 patients had seen their phenylalanine levels fall by 30% or more. The primary endpoint was how far phenylalanine levels had fallen by weeks 5-6 of the study compared to the start. By this point, people who had taken sepiapterin saw a mean phenylalanine reduction of 63%. The treatment was also found to be safe and well-tolerated by patients.
Quick Facts on Phenylketonuria (PKU)
- What is it? PKU is a rare inherited inborn error of metabolism caused by PAH mutations. This gene normally helps the body to produce phenylalanine hydroxylase, an enzyme that breaks down phenylalanine (an amino acid). If too much phenylalanine accumulates in the body, it becomes toxic to the brain.
- How many people are affected? An estimated 1 in every 10,000-15,000 infants are born with PKU. It is usually detected during newborn screening. Early treatment is extremely important.
- Are there symptoms? Yes. PKU can cause symptoms that start in the first few months of life. Early detection and treatment can avoid irreversible complications. Symptoms may include intellectual and developmental delays, an abnormally small head, fair skin and eyes, skin rashes, hyperactivity, depression, reduced bone strength, seizures, heart defects, and a musty odor to the skin, breath, or urine.
- What are the treatments? Phenylalanine is present in protein and artificial sweeteners, so people with PKU need to eliminate these from their diets. Many infants required specialized formula; adults may also supplement with adult formula. Kuvan (sapropterin hydrochloride) may also be used to reduce blood phenylalanine levels.
