Type of information: Granting of a Market Authorisation in the US
Product name: Palynziq® - pegvaliase-pqpz
Compound: PEGylated recombinant phenylalanine ammonia lyase enzyme
Therapeutic area: Rare diseases - Genetic diseases - Metabolic diseases
- enzyme replacement therapy. PEG-PAL (PEGylated recombinant phenylalanine ammonia lyase or ‘PAL’, pegvaliase) is an investigational drug that substitutes for the PAL enzyme in phenylketonuria (PKU) with the PEGylated version of the enzyme phenylalanine lyase, to break down phenylalanine. It is being developed as a potential treatment for adults with inadequately controlled blood phenylalanine levels.
Company: Biomarin Pharmaceutical (USA - CA)
- • On May 24, 2018, the FDA approved Palynziq® (pegvaliase-pqpz) for adults with phenylketonuria (PKU). Patients with PKU are born with an inability to break down phenylalanine (Phe). Palynziq® is a novel enzyme therapy for adult PKU patients who have uncontrolled blood Phe concentrations on current treatment.
- The most common adverse events reported in the Palynziq trials included injection site reactions, joint pain, hypersensitivity reactions, headache, generalized skin reactions lasting at least 14 days, pruritus (itchy skin), nausea, dizziness, abdominal pain, throat pain, fatigue, vomiting, cough and diarrhea. Hypersensitivity reactions occurred in most patients, likely due to formation of antibodies to the product.
- The most serious adverse reaction in the Palynziq® trials was anaphylaxis, which occurred most frequently during upward titration of the dose within the first year of treatment. Because of this serious risk, the labeling for Palynziq® includes a Boxed Warning and the product is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Palynziq REMS Program.
- Palynziq® is expected to be available in the United States by the end of June, and BioMarin will begin the promotion of Palynziq® immediately. Palynziq® is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Palynziq REMS. BioMarin is also committed to bringing Palynziq® to adult PKU patients outside of the United States. In March 2018, the European Medicines Agency accepted BioMarin's submission of a Marketing Authorization Application for Palynziq.
Clinical Trial Results: Palynziq® significantly and substantially reduced blood Phe levels as demonstrated in the pivotal Phase 3 PRISM-2 study, which met the primary endpoint of change in blood Phe compared with placebo (p<0.0001). During the PRISM-2 double-blind, placebo-controlled, randomized withdrawal period trial (RWP), participants were randomized in a 2:1 ratio to either continue their maintenance Palynziq® dosage (20 mg once daily or 40 mg once daily) or to receive matching placebo for a total of 8 weeks. Palynziq-treated patients maintained their blood Phe concentrations as compared to their randomized withdrawal baseline, whereas patients randomized to matching placebo returned to their pretreatment baseline blood Phe concentrations.
In the Phase 3 program, 57% of patients were taking medical food at baseline and 16% were on a protein-restricted diet at baseline (defined as receiving greater than 75% of total protein intake from medical food).
• On March 28, 2018, BioMarin announced that the European Medicines Agency (EMA) has accepted its submission of a Marketing Authorization Application (MAA) for pegvaliase, a PEGylated recombinant phenylalanine ammonia lyase enzyme product, for the treatment of adults with phenylketonuria (PKU) who have inadequate blood phenylalanine control (blood phenylalanine levels greater than 600 micromol/l) despite prior management with available treatment options including sapropterin.
- • On December 22, 2017, BioMarin Pharmaceutical announced that the FDA will require additional time to complete its review of the Biologics License Application (BLA) for its investigational therapy pegvaliase, a PEGylated recombinant phenylalanine ammonia lyase enzyme product, to reduce blood phenylalanine (Phe) levels in adult patients with phenylketonuria (PKU) who have uncontrolled blood Phe levels on existing management. In a notice received from the FDA, the Prescription Drug User Fee Act (PDUFA) Goal Date for pegvaliase has been extended by three months to May 28, 2018. Due to the Memorial Day weekend, the Action Goal Date will be May 25, 2018. The FDA has granted priority review designation to pegvaliase.
- • On August 29, 2017, BioMarin Pharmaceutical announced that the FDA has accepted for Priority Review the Biologics License Application (BLA) for pegvaliase to reduce blood phenylalanine (Phe) levels in adult patients with phenylketonuria who have uncontrolled blood Phe levels on existing management. The PDUFA action date is February 28, 2018. However, the FDA has requested additional Chemistry, Manufacturing, and Controls (CMC) information, which the company expects, when submitted, will be classified as a major amendment and result in a three month extension of the PDUFA date. The Agency has not informed the company whether an advisory committee meeting to discuss the application will be needed.
- • On June 30, 2017, BioMarin Pharmaceutical announced that the company submitted a Biologics License Application (BLA) to the FDA for pegvaliase to reduce blood phenylalanine (Phe) levels in adult patients with PKU who have uncontrolled blood Phe levels on existing management. Following receipt of the BLA, the FDA conducts an initial assessment of the application to determine its fileability. The FDA typically notifies the applicant of their filing decision and planned Prescription Drug User Fee Act (PDUFA) action date within 60 to 74 days after receipt of the application. The company also intends to submit an application for registration in the European Union (EU) by year end 2017.
Submission of marketing authorization application USA : 2017-06-30
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2018-05-24
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: