A PTC Therapeutics drug in development for an inherited metabolic disorder has achieved the main goal of a pivotal study, results that support bringing the therapy to regulators. But less clear is how the drug will match up against a BioMarin Pharmaceutical drug already on the market for the rare disease.
The PTC drug, sepiapterin, is a potential treatment for phenylketonuria (PKU), an inherited deficiency of an enzyme needed to break down an amino acid called phenylalanine. The resulting phenylalanine buildup affects the brain, leading to a wide range of neurological problems. According to South Plainfield, New Jersey-based PTC, PKU affects an estimated 58,000 people globally.
Enzyme replacement is one treatment option for PKU. PTC’s sepiapterin takes a different approach. The small molecule is a precursor to an enzymatic cofactor, a compound that’s needed for an enzyme to carry out its role. This cofactor is involved in metabolism and synthesis of metabolic products.
BioMarin markets two PKU therapies. Palynziq is an enzyme replacement therapy approved for the disorder. Kuvan is likely the more direct competitor to sepiapterin. This BioMarin drug, whose 2007 FDA approval made it the first PKU therapy, has the same mechanism of action as sepiapterin. But PTC did not test its molecule against either of BioMarin’s PKU products. Instead, the 156-patient Phase 3 test compared the drug to a placebo.
Sepiapterin’s Phase 3 study had two parts. In the first part, all screened participants received the study drug for two weeks. Only those who showed a reduction in phenylalanine levels of 15% or greater proceeded to the second part of the study. After a washout period, the responders were randomly assigned to receive the study drug or a placebo for six weeks.
According to the preliminary results released Wednesday, the placebo-controlled portion of the study showed an average 63% reduction in phenylalanine levels in the treatment group compared to minimal reductions in the placebo group. A total of 98 patients were included in this analysis. In a subset of patients with classical PKU, the most severe form of the disorder, the average reduction in phenylalanine was 69%. Specific details about the safety of the drug were not disclosed, but the company said the therapy was well tolerated by study participants.
In an investor presentation, PTC said its drug has the potential to address a broader swath of PKU patients, including those who have the classical form of the disorder as well as those whose disease has not responded to or is not controlled by currently available therapies. The presentation says the results also support discussions with regulators about the pathway to applications seeking approval.
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