New Treatment for Phenylketonuria Approved by FDA


Novel enzyme therapy for adults with PKU, a rare genetic disease, has won approval from the agency.

FDA officials have approved pegvaliase-pqpz (Palynziq, BioMarin Pharmaceutical) for adults with a rare and serious genetic disease, phenylketonuria (PKU). Patients with PKU are born with an inability to break down phenylalanine (Phe), an amino acid present in high-intensity sweeteners and protein-containing foods used in a variety of beverages and foods. Pegvaliase-pqpz is indicated for adult PKU patients who have uncontrolled blood Phe concentrations on current treatment.1

“This is a novel enzyme substitution therapy that helps address a significant unmet need in PKU patients who have been unable to control their blood Phe levels with current treatment options,” Julie Beitz, MD, director of the Office of Drug Evaluation III in the FDA’s Center for Drug Evaluation and Research, said in a statement.1 “This new approval demonstrates our commitment to approving advancements in treatment that will give patients living with PKU different options for care.”

PKU affects about 1 in 10,000 to 15,000 people in the United States. If untreated, PKU can cause chronic intellectual, neurodevelopmental, and psychiatric disabilities. Lifelong restriction of Phe intake through the diet is needed to prevent buildup of Phe in the body, which can cause long-term damage to the central nervous system.1

"Palynziq has the potential to be a game-changing therapy for adults in the PKU community who have struggled throughout their lives to control their Phe levels, despite rigorous management," Christine Brown, MS, executive director of the National PKU Alliance, said in a statement.2 "BioMarin has provided unwavering support for the PKU community and continues innovative medical research to advance treatment options for this rare genetic disease."

The approval of pegvaliase-pqpz was announced this week, during National PKU Awareness Month. It is expected to be made available in the United States by the end of June.2

According to BioMarin and the FDA, Palynziq will only be available through a restricted program under a risk evaluation and mitigation strategy (REMS), known as the Palynziq REMS. In addition, the drug’s labeling will include a boxed warning, because of a risk of anaphylaxis, the most serious reported adverse effect.

Notable requirements of the Palynziq REMS Program include the following:1

  • Patients must enroll in the program and be educated about the risk of anaphylaxis by a certified prescriber to ensure that they understand the benefits and risks of treatment with pegvaliase-pqpz.
  • Patients must have auto-injectable epinephrine available at all times while taking pegvaliase-pqpz.
  • Pharmacies must be certified with the program and must dispense only to patients who are authorized to receive pegvaliase-pqpz.
  • Prescribers must prescribe auto-injectable epinephrine with pegvaliase-pqpz.
  • Prescribers must be certified by enrolling in the REMS program and completing training.

The efficacy and safety of pegvaliase-pqpz were studied in 2 clinical trials in adult patients with PKU with blood Phe concentrations greater than 600 µmol/L on existing management. Most PKU patients in the pegvaliase-pqpz trials were on an unrestricted diet prior to and during the trials.1

The first trial was an open-label, randomized trial in patients treated with increasing doses of pegvaliase-pqpz administered as a subcutaneous injection up to a target dose of either 20 or 40 mg once daily. The second trial was an 8-week, placebo-controlled, randomized withdrawal trial in patients who were previously treated with pegvaliase-pqpz. Patients treated with pegvaliase-pqpz achieved statistically significant reductions in blood Phe concentrations from their pre-treatment baseline blood Phe concentrations.1

The most common adverse effects reported in the pegvaliase-pqpz trials included abdominal pain, cough, dizziness, diarrhea, fatigue, generalized skin reactions lasting at least 14 days, headaches, hypersensitivity and injection site reactions, itchy skin, joint pain, nausea, throat pain, and vomiting.1-2 In cases with anaphylaxis, this serious adverse effect occurred most frequently during upward titration of the dose within the first year of treatment.

The dosing and administration of Palynziq follows an induction, titration, and maintenance paradigm.1 Individualized treatment to the lowest effective and tolerated dosage is recommended. Prescribers may consider increasing dosing to a maximum of 40 mg once daily in patients who have not achieved a response with 20 mg once daily for at least 24 weeks.2 Treatment should be discontinued in patients who have not responded after 16 weeks of continuous treatment with the maximum dosage. Periodic blood Phe monitoring is recommended, and patients should be counseled on how to adjust their dietary intake, as needed, based on blood Phe concentrations.2


  • FDA. FDA approves a new treatment for PKU, a rare and serious genetic disease [news release]. Silver Spring, MD: May 24, 2018; FDA website. Accessed May 24, 2018.
  • BioMarin. BioMarin receives standard approval for Palynziq™ (pegvaliase-pqpz) injection for treatment of adults with phenylketonuria (PKU), a rare genetic disease [news release]. San Rafael, CA: May 24, 2018; Cision website. Accessed May 24, 2018.

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