RARE Daily

FDA Expands Label for BioMarin’s Palynziq

October 7, 2020

Rare Daily Staff

The U.S. Food and Drug Administration expanded the label of BioMarin Pharmaceutical’s Palynziq for adults with phenylketonuria to increase the maximum dose to 60 mg. from 40 mg. 

The company said that in the phase 3 PRISM studies, 19 percent of study participants required a 60 mg dose to achieve adequate response to Palynziq.

PKU, or phenylalanine hydroxylase (PAH) deficiency, is a genetic disorder affecting approximately 70,000 diagnosed patients in the regions of the world where BioMarin operates, and is caused by a deficiency of the enzyme PAH. This enzyme is required for the metabolism of Phe, an essential amino acid found in most protein-containing foods. If the active enzyme is not present in sufficient quantities, Phe accumulates to abnormally high levels in the blood and becomes toxic to the brain, resulting in a variety of complications including severe intellectual disability, seizures, tremors, behavioral problems and psychiatric symptoms.

PKU can be managed with a severe Phe-restricted diet, which is supplemented by low-protein modified foods and Phe-free medical foods; however, it is difficult for most patients to adhere to the life-long strict diet to the extent needed to achieve adequate control of blood Phe levels.  Dietary control of Phe in childhood can prevent major developmental neurological toxicities, but poor control of Phe in adolescence and adulthood is associated with a range of neurocognitive disabilities with significant functional impact.

Palynziq is indicated to reduce blood Phe concentrations in adults with phenylketonuria (PKU), who have uncontrolled blood Phe concentrations greater than 600 μmol/L on existing management.  Palynziq, a PEGylated recombinant phenylalanine ammonia lyase enzyme, is the first and only approved enzyme substitution therapy to target the underlying cause of PKU by helping the body to break down Phe.

The label expansion includes the addition of longer-term efficacy data demonstrating sustained phenylalanine (Phe) lowering out to three years and over six years of data further supporting a well-characterized safety profile. The labeling was updated to allow individualized maintenance dosage to achieve blood Phe control (blood Phe concentrations less than or equal to 600 μmol/L), taking into account patient tolerability to Palynziq and dietary protein intake.

This labeling long term data update is based on efficacy data from an open-label extension study out to three years demonstrating that two-thirds (66 percent) of the 86 participants treated for at least two years, had a blood Phe level ≤360 μmol/L consistent with the Phe target in American College of Medical Genetics and Genomics (ACMG) recommended guidelines, and 50 percent of participants had blood Phe levels ≤120 μmol/L at two years. Of the 77 participants treated for at least three years, 58 (75 percent), 51 (66 percent), and 37 (48 percent) had a blood Phe concentration less than or equal to 600, 360, and 120 μmol /L, respectively, at three years of treatment.  Additional safety data with over six years of follow up remains consistent with the previous safety profile of Palynziq, irrespective of dose.

“Adding a maximum dose of 60 mg allows more patients to optimize and achieve treatment goals to keep blood Phe levels within the range set in the medical guidelines or within normal range,” said Cary Harding, professor at Oregon Health & Science University and Steering Committee Chair for the Palynziq program.  “More than six years of long-term safety data further supports a well-characterized safety profile similar to the initial data and is important information to physicians considering a chronic therapy.”

Photo: Cary Harding, professor at Oregon Health & Science University and Steering Committee chair for the Palynziq program

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