A successful new drug for a rare genetic disease may sound promising for patients, but BioMarin's pegvaliase failed to show benefit in symptoms like mood complications and inattention among patients suffering from phenylalanine hydroxylase (PAH) deficiency.
People suffering from PAH deficiency do not have the enzyme needed to eliminate phenylalanine (Phe) in the blood, an essential amino acid that serves as building blocks for proteins. It cannot be produced by the body so it comes from food.
PAH deficiency is a genetic disease that may lead to a more severe condition called phenylketonuria (PKU) if it's left untreated. PKU is characterized by epilepsy, microcephaly, behavioral problems and severe mental retardation. PAH deficiency is untreatable, but drugs can be used to reduce the effects of increased blood levels of Phe.
BioMarin Pharmaceuticals is a biotechnology firm that developed pegvaliase, a drug aimed at reducing the toxic build-up of the amino acid in the blood of patients suffering from the genetic disorder. Though it achieved this goal, it was not successful enough to reduce symptoms experienced, according to the results of a pivotal Phase III study.
"A therapy in development that shows such a substantial reduction in Phe levels could mean that for the first time, PKU patients who cannot comply with dietary protein restriction, can achieve targeted blood Phe levels," said Dr. Barbara Burton, professor of pediatrics-genetics, birth defects and metabolism at Northwestern School of Medicine and one of the investigators of the study's third phase.
"This pegvaliase study represents an important advance for PKU adult patients and a potentially meaningful treatment," she added.
The company's shares fell as much as 6 percent on Monday morning, after the company released the results of their late-stage study. Despite this, the company plans to pass a marketing application by the end of 2016, which will be subject to further discussions with the U.S. Food and Drug Administration.
Usually, patients will work with doctors and nutritionists to manage the disease with a Phe-restricted diet, which is supplemented with low-protein modified foods. The restricted diet, however, may be difficult for some people to comply to. Therefore, the need to use medications to at least reduce the Phe levels in the body.
The trial drug lowered Phe levels in the blood of patients suffering from PKU by 62 percent compared with those who did not have treatment. Despite achieving the primary endpoint of the eight-week Phase III trials, its failure to show benefit for mood complications and inattention among patients may possibly slow down the adoption of the medicine after launch and approval.
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