Pegvaliase
/api/v1/drug/pegvaliaseBoxed warning
ANAPHYLAXIS Anaphylaxis has been reported after administration of PALYNZIQ and may occur at any time during treatment [see Warnings and Precautions (5.1) ] . Administer the initial dose of PALYNZIQ under the supervision of a healthcare provider equipped to manage anaphylaxis, and closely observe patients for at least 60 minutes following injection. Prior to self-injection, confirm patient competency with self-administration, and patient's and observer's (if applicable) ability to recognize signs and symptoms of anaphylaxis and administer epinephrine, if needed [see Dosage and Administration (2.5) ] . Consider having an adult observer for patients who may need assistance in recognizing and managing anaphylaxis during PALYNZIQ treatment. If an adult observer is needed, the observer should be present during and for at least 60 minutes after PALYNZIQ administration, should be able to administer epinephrine, and call for emergency medical support upon its use [see Warnings and Precautions (5.1) ] . Prescribe epinephrine to all patients treated with PALYNZIQ. Prior to the first dose, instruct the patient and observer (if applicable) how to recognize the signs and symptoms of anaphylaxis, how to properly administer epinephrine, and to seek immediate medical care upon its use.
Mechanism of action
Sourced from openFDAPegvaliase-pqpz is a PEGylated phenylalanine ammonia lyase (PAL) enzyme that converts phenylalanine to ammonia and trans -cinnamic acid. It substitutes for the deficient phenylalanine hydroxylase (PAH) enzyme activity in patients with PKU and reduces blood phenylalanine concentrations.
Indications
Sourced from openFDA- PALYNZIQ is indicated to reduce blood phenylalanine concentrations in adult and pediatric patients 12 years of age and older with phenylketonuria (PKU) who have uncontrolled blood phenylalanine concentrations greater than 600 micromol/L on existing management. PALYNZIQ is a phenylalanine (Phe)-metabolizing enzyme indicated to reduce blood phenylalanine concentrations in adult and pediatric patients 12 years of age and older with phenylketonuria (PKU) who have uncontrolled blood phenylalanine concentrations greater than 600 micromol/L on existing management.
Contraindications
Sourced from openFDA- None. None.contraindicated
Dosage & administration
Sourced from openFDAObtain baseline blood Phe concentration before initiating treatment. ( 2.1 ) Consider premedication for hypersensitivity reactions. ( 2.1 , 5.1 , 5.3 ) The recommended initial dosage for PALYNZIQ is 2.5 mg subcutaneously once weekly for 4 weeks. ( 2.2 ) See the Full Prescribing Information for titration, maintenance, discontinuation, and dose reduction. ( 2.2 ) See Full Prescribing Information for dosage and administration modifications due to anaphylaxis. ( 2.3 ) Obtain blood Phe concentrations every 4 weeks until a maintenance dosage is established. ( 2.4 ) Periodically monitor blood Phe concentrations during maintenance therapy and monitor dietary protein and phenylalanine intake throughout treatment. ( 2.4 ) Rotate injection sites. If more than one injection is needed for a single dose, the injection sites should be at least 2 inches away from each other. ( 2.5 ) 2.1 Important Recommendation Prior to PALYNZIQ Treatment Treatment with PALYNZIQ should be managed by a healthcare provider experienced in the management of PKU. Obtain baseline blood phenylalanine concentration before initiating treatment. Consider premedication with an H 1 -receptor antagonist, H 2 -receptor antagonist, and/or antipyretic based upon individual patient tolerability [see Warnings and Precautions (5.1 , 5.3) ] . 2.2 Recommended Dosage and Administration Induction The recommended initial induction dosage for PALYNZIQ is 2.5 mg subcutaneously once weekly for 4 weeks. Administer the initial dose under the supervision of a healthcare provider [see Dosage and Administration (2.5) ].
Warnings & precautions
Sourced from openFDAHypersensitivity Reactions, Other than Anaphylaxis : Management should be based on the severity of the reaction, recurrence, and clinical judgement. ( 5.3 ) Injection Site Infections : Serious injection site infections, including abscess, cellulitis, necrosis, and ulcer have been reported. Instruct patients to contact their healthcare provider if signs or symptoms of an infection develop, persist, or worsen. ( 5.4 ) Hypophenylalaninemia : Some PKU patients treated with PALYNZIQ have experienced hypophenylalaninemia; monitor blood Phe levels periodically during treatment. ( 5.5 ) 5.1 Anaphylaxis In PALYNZIQ Studies 1, 2, and 3 with an induction/titration/maintenance dosage regimen, 10% (29/285) of PALYNZIQ-treated patients experienced a total of 42 anaphylaxis episodes [see Adverse Reactions (6.1) and Clinical Pharmacology (12.6) ]. The exposure-adjusted rate of anaphylaxis was highest during the induction and titration phases (0.25 episodes/person-years; 5% of PALYNZIQ-treated patients with at least one episode) and decreased in the maintenance phase (0.05 episodes/person-years; 7% of PALYNZIQ-treated patients with at least one episode). Signs and symptoms of anaphylaxis reported in PALYNZIQ-treated patients included syncope, hypotension, hypoxia, dyspnea, wheezing, chest discomfort/chest tightness, tachycardia, angioedema (swelling of face, lips, eyes, tongue), throat tightness, skin flushing, rash, urticaria, pruritus, and gastrointestinal symptoms (vomiting, nausea, diarrhea).
Adverse reactions
Sourced from openFDAThe following serious adverse reactions are discussed below and in other sections of labeling: Anaphylaxis [see Warnings and Precautions (5.1) ] Other Hypersensitivity Reactions [see Warnings and Precautions (5.3) ] Injection Site Infections [see Warnings and Precautions (5.4) ] Hypophenylalaninemia [see Warnings and Precautions (5.5) ] Most common adverse reactions (at least 20% in either treatment phase) are: injection site reactions, arthralgia, hypersensitivity reactions, headache, generalized skin reactions lasting at least 14 days, nausea, abdominal pain, vomiting, cough, oropharyngeal pain, pruritus, diarrhea, nasal congestion, fatigue, dizziness, and anxiety. ( 6.1 ) Most common adverse reactions in patients who are 12 to less than 18 years of age (at least 20% and greater than in control) are: injection site reactions, arthralgia, headache, pyrexia, hypersensitivity reactions, dizziness, nausea, vomiting, fatigue, and pain in extremity. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact BioMarin Pharmaceutical Inc. at 1-866-906-6100, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Use in specific populations
Sourced from openFDA8.1 Pregnancy Risk Summary Available data from pharmacovigilance and published literature with pegvaliase-pqpz use in pregnant women have not identified a clear association with major birth defects, miscarriage or other adverse maternal or fetal outcomes (see Data ) . There are risks to the fetus associated with poorly controlled phenylalanine concentrations in women with PKU during pregnancy including increased risk for miscarriage, major birth defects (including microcephaly and major cardiac malformations), intrauterine fetal growth retardation, and future intellectual disability with low IQ; therefore, phenylalanine concentrations should be closely monitored in women with PKU during pregnancy (see Clinical Considerations and Data ). Advise pregnant women of the potential risks to the fetus. A reproduction study in pregnant rabbits without PKU treated with pegvaliase-pqpz demonstrated a high incidence of fetal malformations throughout the skeletal system, and in kidneys, lungs, and eyes. Embryo-fetal toxicity (increased resorptions and reduced fetal weight) was also observed. These effects occurred at 5 times the maximum recommended daily dose and were associated with strong signs of maternal toxicity, including marked reductions in weight gain and food consumption, and death.
Pharmacokinetics
Sourced from openFDA- Metabolism
- The pharmacokinetics of pegvaliase-pqpz exhibit high inter-patient and intra-patient variability due to the heterogeneity of the immune response in adult patients with PKU. Higher antibody titers correlated with higher apparent clearance of pegvaliase-pqpz.
Approval history
Sourced from openFDA- May 24, 2018BLABLA761079Biomarin Pharm
FAERS reports
- 1Arthralgia1,35617%
- 2Injection Site Reaction88511%
- 3Injection Site Erythema7219.1%
- 4Injection Site Swelling5316.7%
- 5Rash4886.2%
- 6Urticaria4826.1%
- 7Headache4265.4%
- 8Injection Site Pain4145.2%
- 9Fatigue3684.6%
- 10Injection Site Pruritus3534.5%
- 11Hypersensitivity3334.2%
- 12Pruritus3304.2%
- 13Off Label Use3224.1%
- 14Dizziness3194.0%
- 15Anaphylactic Reaction3184.0%
Clinical trials
The 10 most recently updated of 20 ClinicalTrials.gov registrations naming Pegvaliase as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.
- Nutrition Status of Adults With PKU Before and During Treatment With PegvaliaseCompleted · Observational · 12 enrolled · Boston Children's HospitalNCT03856203updated 2026-06-02
- Rapid Drug Desensitization Study in Adults Experiencing Hypersensitivity Reactions to PalynziqActive not recruiting · Phase 4 · Interventional · 9 enrolled · BioMarin PharmaceuticalNCT06780332updated 2026-04-03
- A Long-term, Post-marketing Safety Study of Palynziq in Patients With PKU (PALace)Recruiting · Observational · 450 enrolled · BioMarin PharmaceuticalNCT05813678updated 2026-03-25
- A Long Term, Post-marketing Study of Immune Response in Patients Receiving Palynziq Treatment for PKU (PALisade)Recruiting · Observational · 200 enrolled · BioMarin PharmaceuticalNCT06305234updated 2026-03-24
- A Global, Multicenter Study to Assess Maternal, Fetal and Infant Outcomes of Exposure to Palynziq® (Pegvaliase) During Pregnancy and BreastfeedingRecruiting · Observational · 50 enrolled · BioMarin PharmaceuticalNCT05579548updated 2026-03-24
- Immune Modulation During Palynziq® Treatment in Adults (IMPALA)Not yet recruiting · Phase 4 · Interventional · 12 enrolled · BioMarin PharmaceuticalNCT07477691updated 2026-03-17
- Nutritional Impacts of Palynziq on Patients With Phenylketonuria (PKU)Recruiting · Observational · 45 enrolled · Emory UniversityNCT04404530updated 2026-01-14
- Preliminary Study of Brain Effects of Palynziq-Related Changes in Phenylalanine in Individuals With PKUCompleted · Observational · 6 enrolled · University of Missouri-ColumbiaNCT05356377updated 2025-12-29
- Study to Evaluate the Safety and Efficacy of Pegvaliase in Adolescents (Ages 12-17) With PhenylketonuriaActive not recruiting · Phase 3 · Interventional · 55 enrolled · BioMarin PharmaceuticalNCT05270837updated 2025-09-12
- Safety and Efficacy of Self Administered Injections of Pegvaliase (>40mg/Day Dose) in Adults With PKUCompleted · Phase 3 · Interventional · 37 enrolled · BioMarin PharmaceuticalNCT03694353updated 2022-02-17
Frequently asked questions
- How does Pegvaliase work?
- Pegvaliase-pqpz is a PEGylated phenylalanine ammonia lyase (PAL) enzyme that converts phenylalanine to ammonia and trans -cinnamic acid. It substitutes for the deficient phenylalanine hydroxylase (PAH) enzyme activity in patients with PKU and reduces blood phenylalanine concentrations.
- What is Pegvaliase used for?
- According to FDA labeling, Pegvaliase carries indications including: PALYNZIQ is indicated to reduce blood phenylalanine concentrations in adult and pediatric patients 12 years of age and older with phenylketonuria (PKU) who have uncontrolled blood phenylalanine concentrations greater than 600 micromol/L on existing management. PALYNZIQ is a phenylalanine (Phe)-metabolizing enzyme indicated to reduce blood phenylalanine concentrations in adult and pediatric patients 12 years of age and older with phenylketonuria (PKU) who have uncontrolled blood phenylalanine concentrations greater than 600 micromol/L on existing management.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.
- What class of drug is Pegvaliase?
- Pegvaliase is classified as Enzymes, Phenylalanine Metabolizing Enzyme, Enzyme Interactions.
- What are the brand names for Pegvaliase?
- Pegvaliase is marketed under brand names including Palynziq.
- What are the contraindications for Pegvaliase?
- Pegvaliase labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.
pegvaliase is illustrative MVP content compiled from public sources. pharmacopeia is for educational and informational use only and is not a substitute for professional medical advice.