Brand Name
Palynziq
Generic Name
Pegvaliase-Pqpz
View Brand Information FDA approval date: May 24, 2018
Classification: Phenylalanine Metabolizing Enzyme
Form: Injection
What is Palynziq (Pegvaliase-Pqpz)?
Palynziq is indicated to reduce blood phenylalanine concentrations in adult patients with phenylketonuria who have uncontrolled blood phenylalanine concentrations greater than 600 micromol/L on existing management. Palynziq is a phenylalanine ‑metabolizing enzyme indicated to reduce blood Phe concentrations in adult patients with phenylketonuria who have uncontrolled blood Phe concentrations greater than 600 micromol/L on existing management.
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Related Clinical Trials
A Phase 4 Study to Evaluate the Impact of a Rapid Drug Desensitization (RDD) Protocol for Adults with Phenylketonuria and Experiencing Hypersensitivity Reactions to Palynziq
Summary: The purpose of this study is to determine if rapid drug desensitization (RDD) to Palynziq will improve drug tolerability and treatment persistence in adult patients on commercial Palynziq experiencing hypersensitivity reactions (HSRs) leading to treatment interruption or reduction of dose or dosing frequency. See Section 10.8 for full list of HSR preferred terms. Study details include: * Study dur...
Palynziq and PKU: Treatment Impacts on Diet Quality, Neurological Health, Nutritional Status, and the Metabolome
Summary: Phenylketonuria (PKU) is an inherited metabolic disorder that impairs the metabolism of the essential amino acid phenylalanine (Phe). Without stringent dietary control, Phe accumulates in the blood and brain of PKU patients, leading to severe cognitive deficits. Achieving metabolic control, defined as blood Phe levels within the range of 120-360 μmol/L, has been a significant challenge for PKU pat...
A Multi-Center, Prospective, Longitudinal, Study Evaluating Immunologic, Inflammatory, and Laboratory Parameters Associated With Long-Term Palynziq® (Pegvaliase) Treatment in Subjects With Phenylketonuria (PKU) in the United States
Summary: This is a 10-year multi-center, prospective, longitudinal, single arm study evaluating immunologic, inflammatory and laboratory parameters associated with long-term Palynziq treatment in subjects with phenylketonuria (PKU) in the United States (US). Subjects in the US for whom a clinical decision has been made that they will receive pegvaliase to treat their PKU within 30 days following the date o...
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Brand Information
Palynziq (pegvaliase-pqpz)
WARNING: RISK OF ANAPHYLAXIS
Anaphylaxis has been reported after administration of Palynziq and may occur at any time during treatment 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 auto‑injectable epinephrine, if needed 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 auto‑injectable epinephrine, and call for emergency medical support upon its use Prescribe auto‑injectable 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 auto‑injectable epinephrine, and to seek immediate medical care upon its use. Instruct patients to carry auto‑injectable epinephrine with them at all times during treatment with Palynziq Consider the risks and benefits of readministering Palynziq following an episode of anaphylaxis. If the decision is made to readminister Palynziq, readminister the first dose under the supervision of a healthcare provider equipped to manage anaphylaxis and closely observe the patient for at least 60 minutes following the dose Because of the risk of anaphylaxis, Palynziq is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Palynziq REMS
1INDICATIONS AND USAGE
Palynziq is indicated to reduce blood phenylalanine concentrations in adult patients with phenylketonuria (PKU) who have uncontrolled blood phenylalanine concentrations greater than 600 micromol/L on existing management.
2DOSAGE FORMS AND STRENGTHS
Palynziq is a clear to slightly opalescent, colorless to pale yellow solution available as follows:
- Injection: 2.5 mg/0.5 mL single-dose prefilled syringe
- Injection: 10 mg/0.5 mL single-dose prefilled syringe
- Injection: 20 mg/mL single-dose prefilled syringe
3CONTRAINDICATIONS
None.
4ADVERSE REACTIONS
The following serious adverse reactions are discussed below and in other sections of labeling:
- Anaphylaxis
- Other Hypersensitivity Reactions
4.1Clinical 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.
The data described below reflect a total treatment exposure of 789 patient-years in 285 patients who received Palynziq in an induction/titration/maintenance regimen in clinical trials
The most common adverse reactions (at least 20% of patients in either treatment phase) were 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.
Of the 285 patients exposed to Palynziq in an induction/titration/maintenance regimen in clinical trials, 44 (15%) patients discontinued treatment due to adverse reactions. The most common adverse reactions leading to treatment discontinuation were hypersensitivity reactions (6% of patients) including anaphylaxis (3% of patients), angioedema (1% of patients), arthralgia (4% of patients), generalized skin reactions lasting at least 14 days (2% of patients), and injection site reactions (1% of patients).
The most common adverse reactions leading to dosage reduction were arthralgia (15% of patients), hypersensitivity reactions (9% of patients), injection site reactions (4% of patients), alopecia (3% of patients), and generalized skin reactions lasting at least 14 days (2% of patients).
The most common adverse reactions leading to temporary drug interruption were hypersensitivity reactions (14% of patients), arthralgia (13% of patients), anaphylaxis (4% of patients), and injection site reactions (4% of patients).
Table 2 lists adverse reactions reported in at least 15% of patients treated with Palynziq in an induction/titration/maintenance dosage regimen in clinical trials, and illustrates the adverse reaction rates over time by treatment phase. Table 3 lists laboratory abnormalities reported in at least 10% of patients treated with Palynziq in an induction/titration/maintenance dosage regimen in clinical trials.
For these analyses, the induction/titration phase was defined as the time prior to reaching a stable dose (completing an 8‑week phase at the same dose level). Once a stable dosage was reached, patients were considered to be in the maintenance phase thereafter. Safety data for patients who reached the maintenance phase are included within either the induction/titration or maintenance phases depending on the onset date of the adverse reaction. Safety data for patients who did not reach the maintenance phase are included within the induction/titration phase. The maintenance phase includes data for patients who were previously on Palynziq and transitioned to placebo during the randomized withdrawal period of Study 302
Rates of adverse reactions (adjusted for duration of exposure) generally decreased over time and for some stayed relatively stable. In the maintenance phase, the rate of adverse reactions (adjusted for duration of exposure) in patients who reached the maintenance phase was comparable across dosages evaluated. The types and rate of adverse reactions reported during the maintenance phase in patients who received 20 mg once daily, 40 mg once daily, and 60 mg once daily were similar. During long-term treatment (greater than 36 months), the exposure-adjusted rates of adverse reactions decreased.
Rates of laboratory abnormalities (adjusted for duration of exposure) stayed relatively stable over time, except for complement C4 below lower limit of normal (LLN) and hs-CRP above 0.287 mg/dL over a 6 month period (both decreased over time) and hypophenylalaninemia (blood phenylalanine concentration below 30 micromol/L) on a single measurement (increased over time). There were no dose‑related trends in type or rate of laboratory abnormalities (adjusted for duration of exposure) reported during the maintenance phase in patients receiving 20 mg once daily, 40 mg once daily, or 60 mg once daily.
LLN – lower limit of normal
ULN – upper limit of normal
Hs – high sensitivity
Description of Selected Adverse Reactions
Arthralgia
In clinical trials, 245 out of 285 (86%) patients experienced episodes consistent with arthralgia (includes back pain, musculoskeletal pain, pain in extremity, and neck pain).
Arthralgia episodes were more frequent during the induction/titration phase (7.4 episodes/patient-year) and decreased over time (1.4 episodes/patient-year in the maintenance phase).
Forty-four out of 285 (15%) patients had one episode of arthralgia, 32 (11%) patients had 2 episodes of arthralgia, 18 (6%) had 3 episodes of arthralgia, and 146 (51%) had 4 or more episodes of arthralgia. Arthralgia occurred as early as after the first dose of Palynziq and occurred at any time during treatment. The mean duration of arthralgia was 16 days (median: 3 days, range: 1 to 936 days), and 19% of arthralgia episodes had a duration of at least 14 days. Severe arthralgia (severe pain limiting self-care activities of daily living) was reported by 11 (4%) patients. In addition to arthralgia, other joint-related signs and symptoms reported were: joint swelling (24 patients; 8%), joint stiffness (22 patients; 8%), and musculoskeletal stiffness (20 patients; 7%). Arthralgia episodes were managed with medications (e.g., nonsteroidal anti-inflammatory drugs, glucocorticoids, and acetaminophen), Palynziq dosage reduction (4% of episodes), Palynziq interruption (4% of episodes), or Palynziq withdrawal (0.6% of episodes). 97% of arthralgia episodes were reported as resolved at the time of last observation (up to 77 months of follow‑up).
Injection Site Reactions
Injection site reactions were reported as early as after the first dose of Palynziq and occurred at any time during treatment. Injection site reactions were more frequent during the induction/titration phase (21 episodes/patient-years) and decreased over time (3 episodes/patient‑years in the maintenance phase). The mean duration of injection site reaction was 10 days (median: 2 days, range: 1 to 1612 days), and 8% of injection site reactions had a duration of at least 14 days. 99% of injection site reactions were reported as resolved at the time of last observation (up to 77 months of follow‑up).
Three injection site reactions consistent with granulomatous skin lesions were reported (each reaction occurring in one patient): granulomatous dermatitis (occurred after 464 days of Palynziq treatment and lasted 16 days), xanthogranuloma (occurred after 378 days of Palynziq treatment and lasted 638 days) was treated with a topical antihistamine, corticosteroid, and Palynziq treatment was discontinued, and necrobiosis lipoidica diabeticorum (occurred after 281 days of Palynziq treatment and lasted 281 days). Necrobiosis lipoidica diabeticorum was treated with steroid injections and complicated by
One patient reported soft tissue infection (occurred after 196 days of Palynziq treatment and lasted 8 days) associated with mesenteric panniculitis treated with antibiotics, which resulted in treatment discontinuation.
Generalized Skin Reactions (not limited to the injection site) Lasting at Least 14 Days
In clinical trials, 134 out of 285 (47%) patients treated with Palynziq experienced generalized skin reactions (not limited to the injection site) lasting at least 14 days. Mean duration of these reactions was 63 days (median: 37 days; range: 14 to 638 days). Generalized skin reactions were more frequent during the induction/titration phase (0.7 episodes/patient‑years), and decreased over time (0.3 episodes/patient-years in the maintenance phase).
The mean time from first dose of Palynziq to onset of skin reactions was 373 days (median: 213 days; range: 2 to 1970 days). 5% of these reactions persisted at least 180 days, and 86% of these reactions were reported as resolved at the time of last observation (up to 77 months of follow‑up).
Angioedema
In clinical trials, 22 out of 285 (8%) patients experienced 45 episodes of angioedema (symptoms included: pharyngeal edema, swollen tongue, lip swelling, mouth swelling, eyelid edema and face edema) occurring independent of anaphylaxis. Angioedema (included under Hypersensitivity in Table 2) was more frequent during the induction/titration phase (0.14 episodes/patient-year) and decreased over time (0.04 episodes/patient-year in the maintenance phase). Three patients discontinued treatment. All episodes resolved. Angioedema can present as a symptom of anaphylaxis
Serum Sickness
In clinical trials, serum sickness was reported in 7 out of 285 (2%) patients. Serum sickness episodes were more frequent during the induction/titration phase (0.04 episodes/patient-year) and decreased over time (less than 0.01 episodes/patient-year during the maintenance phase). All serum sickness reactions resolved without sequelae (duration of serum sickness ranged from 1 to 8 days). Out of the 7 patients who experienced serum sickness, 5 patients continued treatment without a recurrence, and managed serum sickness with drug interruption, dosage reduction and/or concomitant medication. Two patients discontinued treatment.
4.2Post-Marketing Experience
The following adverse reactions have been identified during post-approval use of Palynziq. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Administration site conditions: injection site infection, cellulitis, necrosis, and abscess.
4.3Immunogenicity
As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Palynziq in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.
All patients treated with Palynziq developed a sustained total anti-drug antibody (TAb) response with a majority of patients (91%; N = 235/258) developing that response by Week 4 of treatment. Mean TAb titers peaked 2 weeks after Palynziq initiation and remained elevated throughout treatment (greater than 3 years after treatment initiation). Anti-phenylalanine ammonia lyase (PAL) IgM antibodies were detected in a majority of patients (98%; N = 265/270) by 2 months after treatment initiation, with incidence declining over time to 67% at 36 months (N = 114/171). Anti‑PAL IgG antibodies were detected in almost all patients (N = 226/227) by 4 months after treatment initiation. Mean anti-PAL IgM and IgG titers peaked at approximately 3 and 6 months, respectively, after treatment initiation and remained elevated throughout treatment (greater than 3 years after treatment initiation). Drug-induced anti-PEG IgM and IgG antibodies were detected in the majority of patients (98%; N = 277/284 for IgM; and 278/284 for IgG) with mean titers for both peaking at 1 to 3 months after treatment initiation
Twenty-seven of 29 patients who had anaphylaxis were tested for anti‑pegvaliase‑pqpz IgE antibodies, which recognize the PEGylated protein product. Of the 27 patients tested for anti‑pegvaliase‑pqpz IgE antibodies, 26 patients tested negative. The one patient who tested positive for anti‑pegvaliase‑pqpz IgE antibodies on the screening test did not have sufficient sample to confirm IgE positivity. This patient tested negative for anti‑pegvaliase‑pqpz IgE at routine visits prior to and after the anaphylaxis episode (not at times of anaphylaxis). Sixty‑seven of 285 patients in clinical trials were tested for both anti‑PAL IgE antibodies, which recognize the recombinant PAL protein, and for anti‑pegvaliase‑pqpz IgE antibodies during routine study visits (not at times of anaphylaxis episodes) or during additional visits for hypersensitivity reactions. Of those 67 patients, 5 (8%) tested positive at least once for anti‑PAL IgE antibodies but negative for anti‑pegvaliase‑pqpz IgE antibodies.
The highest frequency of hypersensitivity reactions (consistent with a Type III immune complex-mediated hypersensitivity mechanism) occurred within the first 6 months of Palynziq treatment when the mean circulating immune complex (CIC) concentrations were at their highest and mean complement C3 and C4 concentrations were at their lowest. Mean CIC concentrations decreased and complement levels increased over time as the exposure-adjusted rate of hypersensitivity reactions decreased. IgG and IgM CIC concentrations were above the upper limit of normal in 63% (N = 164/259) and 42% of patients (N = 109/259), respectively, at 12 weeks of Palynziq treatment and returned towards baseline with long-term treatment (greater than 3 years after treatment initiation). 61% of patients (N = 110/180) had complement C3 concentrations less than lower limit of normal (LLN) at 6 months after treatment initiation and 38% of patients (N = 94/248) had complement C4 concentrations less than LLN at 3 months after treatment initiation. The incidence of low complement C3 and C4 concentrations decreased over time, but approximately 35% (N = 34/96) and 12% (N = 11/96) of patients had low C3 and C4 concentrations, respectively, at 36 months after treatment initiation.
Higher antibody responses for all antibody analytes, including NAb, were associated with lower mean trough pegvaliase‑pqpz concentrations and with higher blood phenylalanine concentrations. Hypersensitivity reactions occurred more frequently in patients with higher antibody titers for some but not all antibody analytes. Patients with higher mean change in IgG CIC concentrations from pre-treatment baseline tended to have higher discontinuation rates than patients with lower mean change in IgG CIC concentrations. Mean antibody titers for anti‑PAL IgG and IgM, TAb, and NAb remained relatively stable with long-term treatment.
5DESCRIPTION
Pegvaliase-pqpz is a phenylalanine-metabolizing enzyme that is composed of recombinant phenylalanine ammonia lyase (rAvPAL) conjugated to N-hydroxysuccinimide (NHS)-methoxypolyethylene glycol (PEG). rAvPAL is manufactured in
Palynziq (pegvaliase‑pqpz) injection, intended for subcutaneous injection, is a clear to slightly opalescent, colorless to pale yellow, sterile, preservative-free solution and is formulated at pH 6.6 to 7.4.
Palynziq is provided in a single-dose prefilled syringe and is available in three dosage strengths: 2.5 mg/0.5 mL, 10 mg/0.5 mL, and 20 mg/mL. Palynziq contents for each dosage strength are summarized in Table 4.
6CLINICAL STUDIES
Study 301: Induction/Titration/Maintenance Treatment
Study 165‑301 (referred to as Study 301, NCT01819727) was an open-label randomized, multi-center study of adults with PKU to assess safety and tolerability of self-administered Palynziq in an induction/titration/maintenance regimen with a target maintenance dose of 20 mg subcutaneously once daily or 40 mg subcutaneously once daily. At Palynziq treatment initiation, 253 patients demonstrated inadequate blood phenylalanine control (blood phenylalanine concentration greater than 600 micromol/L) on existing management, and 8 patients had blood phenylalanine concentrations less than or equal to 600 micromol/L. Existing management options included prior or current restriction of dietary phenylalanine and protein intake, and/or prior treatment with sapropterin dihydrochloride. Patients previously treated with sapropterin dihydrochloride were required to discontinue use at least 14 days prior to the first dose.
The 261 enrolled patients were aged 16 to 55 years (mean: 29 years) and had a baseline mean (range) blood phenylalanine of 1,233 (285, 2330) micromol/L. One hundred forty nine out of 261 (57%) patients were taking medical food at baseline and 41 out of 261 patients (16%) were on a protein-restricted diet at baseline (defined as receiving greater than 75% of total protein intake from medical food). Patients were randomized (1:1) to one of two target maintenance dosage arms: 20 mg once daily or 40 mg once daily. Patients were titrated to reach their randomized target dosage of 20 mg once daily or 40 mg once daily. The duration of titration varied among patients and was based on patient tolerability. Of the 261 enrolled patients, 195 (75%) patients reached their randomized maintenance dosage (103 in the 20 mg once daily arm, 92 in the 40 mg once daily arm). Among the patients who reached their randomized maintenance dosage, patients in the 20 mg once daily randomized arm reached their maintenance dosage at a median time of 10 weeks (range: 9 to 29 weeks) and patients in the 40 mg once daily arm reached their maintenance dosage at a median time of 11 weeks (range: 10 to 33 weeks).
Of the 261 patients who enrolled in Study 301, 54 (21%) patients discontinued treatment during Study 301, 4 patients completed Study 301 and did not continue to Study 165‑302 (referred to as Study 302, NCT01889862), 152 patients continued to the eligibility period of Study 302, and 51 patients continued directly from Study 301 into the long‑term treatment period of Study 302.
Study 302: Efficacy Assessment
A total of 164 adult patients with PKU who were previously-treated with Palynziq (152 patients from Study 301 and 12 patients from other Palynziq trials) enrolled in Study 302 and continued treatment with Palynziq in Study 302 for up to 13 weeks to assess eligibility for randomized withdrawal period.
Randomized Withdrawal Period
Following this period of up to 13 weeks of additional Palynziq treatment in Study 302, eligibility for entry into the efficacy assessment period (randomized withdrawal period) was determined by whether a patient achieved at least a 20% reduction in blood phenylalanine concentration from pre-treatment baseline (when in previous studies). Eighty‑six out of 164 patients (52%) met this response target and continued into the randomized withdrawal period. In the double-blind, placebo-controlled, randomized withdrawal period, patients were randomized in a 2:1 ratio to either continue their maintenance Palynziq dosage or to receive matching placebo for a total of 8 weeks. The treatment difference in least squares (LS) mean change in blood phenylalanine concentration from the Study 302 randomized withdrawal baseline to randomized withdrawal Week 8 for each randomized study arm is shown in Table 5. Mean blood phenylalanine concentrations at pre-treatment baseline (Study 301 or other Palynziq trials) are also shown in Table 5. At Study 302 randomized withdrawal Week 8, Palynziq‑treated patients (20 mg once daily or 40 mg once daily) maintained their blood phenylalanine concentrations as compared to their randomized withdrawal baseline, whereas patients randomized to matching placebo (20 mg once daily or 40 mg once daily) returned to their pretreatment baseline blood phenylalanine concentrations (Figure 1).
Figure 1: Observed Mean (SE) Blood Phenylalanine Concentrations Over Time in Adult Patients with PKU in Study 302
Study 301 and 302 Continuous Treatment
Of 118 patients from Study 301 with a pre‑treatment baseline blood phenylalanine concentration greater than 600 micromol/L who were randomized to and received at least one dose of 20 mg once daily Palynziq, 107 patients, 97 patients, 93 patients, 86 patients, and 77 patients were treated for at least 6 months, 12 months, 18 months, 24 months, and 36 months, respectively. During the continuous treatment period, patients were allowed to dose up to 60 mg once daily based on investigator discretion to achieve blood phenylalanine lowering (for example, to achieve blood phenylalanine concentrations between 120 and 360 micromol/L).
Of the 118 patients, a majority (91 patients, 77%) reached their first response, defined as a blood phenylalanine concentration less than or equal to 600 micromol/L, at a time point prior to 36 months. Of the 91 patients, 9 patients (10%) achieved their first response at a dose less than 20 mg once daily, 44 patients (48%) achieved their first response at a dose of 20 mg once daily, 26 patients (29%) achieved their first response at a dose of 40 mg once daily, and 12 patients (13%) achieved their first response at a dose of 60 mg once daily. Of the 44 patients that achieved their first response at a dose of 20 mg once daily, 36 (82%) achieved it by 24 weeks of treatment. Of the 26 patients that achieved their first response at a dose of 40 mg once daily, 18 (69%) achieved it by 16 weeks of treatment. Of the 12 patients that achieved their first response at a dose of 60 mg once daily, 8 (67%) achieved it by 16 weeks of treatment.
Of the 107 patients treated for at least 6 months, 28 (26%), 18 (17%), and 11 (10%) had a blood phenylalanine concentration less than or equal to 600, 360, and 120 micromol/L, respectively, at 6 months of treatment. Of the 97 patients treated for at least 12 months, 47 (48%), 41 (42%), and 31 (32%) had a blood phenylalanine concentration less than or equal to 600, 360, and 120 micromol/L, respectively, at 12 months of treatment. Of the 93 patients treated for at least 18 months, 64 (69%), 46 (49%), and 36 (39%) had a blood phenylalanine concentration less than or equal to 600, 360, and 120 micromol/L, respectively, at 18 months of treatment. Of the 86 patients treated for at least 24 months, 65 (76%), 57 (66%), and 43 (50%) had a blood phenylalanine concentration less than or equal to 600, 360, and 120 micromol/L, respectively, at 24 months of treatment. Of the 77 patients treated for at least 36 months, 58 (75%), 51 (66%), and 37 (48%) had a blood phenylalanine concentration less than or equal to 600, 360, and 120 micromol/L, respectively, at 36 months of treatment.
7HOW SUPPLIED/STORAGE AND HANDLING
How Supplied
Palynziq (pegvaliase-pqpz) injection is supplied as a preservative-free, sterile, clear to slightly opalescent, colorless to pale yellow solution. All dosage strengths of Palynziq are provided in a 1 mL glass syringe with a 26 gauge, 0.5 inch needle.
Each carton contains 1 or 10 trays with single-dose prefilled syringe(s), Prescribing Information, Medication Guide, and Instructions for Use. The following packaging configurations are available.
Storage and Handling
- Store in refrigerator at 36°F to 46°F (2°C to 8°C) in its original carton to protect from light.
- Do not freeze or shake.
- For patients: If needed, store Palynziq in the original carton at room temperature between 68°F to 77°F (20°C to 25°C) for up to 30 days. Record the date removed from refrigeration on the carton. Once stored at room temperature, do not return the product to the refrigerator.
- The shelf-life expires after storage at room temperature for 30 days, or after the expiration date on the product carton, whichever is earlier.
8PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (
Anaphylaxis and Other Hypersensitivity Reactions
- Advise patients that Palynziq may cause hypersensitivity reactions, including anaphylaxis that can occur at any time. Instruct patients to recognize the signs and symptoms of anaphylaxis
- Instruct patients to carry auto-injectable epinephrine with them at all times during Palynziq treatment. Instruct the patient and observer (if applicable) on the appropriate use of auto‑injectable epinephrine for anaphylaxis
- Instruct patients who experience anaphylaxis to seek immediate medical care, discontinue therapy, and resume treatment only at the instruction of a healthcare provider
Palynziq REMS Program
Palynziq is available only through a restricted program called the Palynziq REMS
- Patients must be enrolled in the Palynziq REMS.
- Patients must be educated about the risk of anaphylaxis by a certified prescriber to ensure they understand the risks and benefits of treatment with Palynziq.
- Patients must fill a prescription for auto-injectable epinephrine and carry it with them at all times.
- Patients will be given a Palynziq Patient Wallet Card that they should carry with them at all times. This card describes symptoms which, if experienced, should prompt the patient and observer (if applicable) to immediately seek medical care. Advise the patient to show the Palynziq Wallet Card to other treating healthcare providers.
Palynziq is available only from certified pharmacies participating in the program. Therefore, provide patients with the telephone number and website for information on how to obtain the product.
Administration
- Advise patients to monitor their dietary protein and phenylalanine intake throughout treatment with Palynziq, and adjust intake as directed by their healthcare provider based on blood phenylalanine concentrations
- Provide appropriate instruction for methods of self-injection, including careful review of the Palynziq Medication Guide and Instructions for Use. Instruct patients in the use of aseptic technique when administering Palynziq
- Inform patients that a healthcare provider will show them or their caregiver how to prepare to inject Palynziq before self-administering.
- Advise patients not to inject into moles, scars, birthmarks, bruises, rashes, or areas where the skin is hard, tender, red, damaged, burned, inflamed, or tattooed.
- Advise patients to rotate areas of injection with each dose.
- Advise patients that injection site infections may occur and to check the injection site for redness, swelling, or tenderness prior to injection. Instruct patients to contact their healthcare provider if signs or symptoms of an infection develop, persist, or worsen
- Advise patients to not administer Palynziq into the affected area until the infection has resolved.
- Advise patients to follow sharps disposal recommendations
- Advise patients that the shelf‑life expires after storage at room temperature for 30 days or after the expiration date on the product carton, whichever is earlier.
Pregnancy
- Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females to inform their healthcare provider of a known or suspected pregnancy
- Advise women who are exposed to Palynziq during pregnancy or who become pregnant within one month following the last dose of Palynziq that there is a pregnancy surveillance program that monitors pregnancy outcomes. Encourage these patients to report their pregnancy to BioMarin (1‑866‑906‑6100)
Manufactured by:
BioMarin Pharmaceutical Inc.
Novato, CA 94949
US License No. 1649
9INSTRUCTION FOR USE
Instructions for Use
Palynziq (Pal-lin-zeek)
(pegvaliase-pqpz)
Injection for Subcutaneous Use
Single-Dose Prefilled Syringe
Read this Instructions for Use before you start using the Palynziq prefilled syringe and each time you get a new prescription. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.
Follow these instructions carefully while you are using Palynziq. If your healthcare provider decides that you (or your caregiver) can give the injections of Palynziq at home, your healthcare provider will show you (or your caregiver) how to inject Palynziq the right way. Your healthcare provider should watch you (or your caregiver) give the first Palynziq injection and monitor you for signs and symptoms of a severe allergic reaction (anaphylaxis).
Talk to your healthcare provider if you (or your caregiver) have any questions about how to inject Palynziq the right way.
Do not share your prefilled syringes with anyone else. You may give an infection to them or get an infection from them.
Store your Palynziq prefilled syringe(s) in its original carton in the refrigerator. See “Storage of Palynziq” at the end of this Instructions for Use.
Supplies you will need for each injection of Palynziq (See Figure A):
Palynziq prefilled syringe(s) in sealed tray(s). 1 gauze pad or cotton ball 1 alcohol pad 1 bandage 1 puncture resistant or sharps disposal container. See
Figure A
Important things to know about using your Palynziq prefilled syringe:
Inject only 1 time with each Palynziq prefilled syringe. Do not pull back on the plunger at any time. Do not remove the needle cap until you are ready to inject.
Figure B below shows what the prefilled syringe looks like before use.
Figure B
Select the correct Palynziq prefilled syringe(s) for your dose. You may need more than 1 prefilled syringe for your prescribed dose. Your healthcare provider will tell you which syringe(s) to use. Ask your healthcare provider if you have any questions.
When you receive your Palynziq prefilled syringe(s), check that the name “Palynziq" appears on the carton(s).
Palynziq prefilled syringes come in 3 different strengths (See Figure C). Before you inject Palynziq, check each carton and syringe to make sure you have the right prefilled syringe for your prescribed dose.
Figure C
Set up your injection
Step 1: Gather your supplies for the injection(s) (See Figure A) and place them on a clean flat surface.
Take out the number of cartons needed for your prescribed dose from the refrigerator.
Check the expiration date (EXP) on the carton(s) (See Figure D).
- If the expiration date has passed,
Figure D
Step 2: Open the carton(s) and take out the sealed tray(s) that you need for your prescribed dose (See Figure E). You may need more than 1 prefilled syringe for your prescribed dose.
Place the sealed tray(s) on a clean, flat surface out of reach of children and pets.
Put the carton with any remaining trays back in the refrigerator.
Figure E
Step 3: Let the sealed tray(s) sit at room temperature for at least 30 minutes. Injecting Palynziq when cold can make the injection feel uncomfortable.
- Do not warm up the prefilled syringe in any other way other than letting it sit at room temperature. Do not warm in a microwave and do not place in hot water.
Step 4: Peel off the cover from the tray (See Figure F).
Figure F
Step 5: Hold the middle of the prefilled syringe body and remove the prefilled syringe from the tray (See Figure G).
- Throw away the prefilled syringe if it looks damaged or used, and use a new prefilled syringe for your injection. See “Dispose of the used prefilled syringes” at the end of this Instructions for Use. Call BioMarin at 1‑866‑906‑6100 or your healthcare provider for help with Palynziq.
- Do not remove the needle cap from the prefilled syringe until Step 12.
- Do not shake or roll the syringe in your hands.
Figure G
Step 6: Check the prefilled syringe label to make sure you have the correct strength for your prescribed dose.
Step 7: Look at the liquid through the viewing window (See Figure H).
- It is normal to see air bubbles.
The liquid should look clear and colorless to pale yellow.
Figure H
Choose and prepare injection site
Step 8: Choose your injection site.
The recommended injection sites are:
- Front middle of the thighs.
- The abdomen except for the 2 inch (5 centimeter) area directly around the belly button (navel).
Figure I
If a caregiver is giving the injection, the top of the buttocks and the back of the upper arms may also be used (See Figure I).
- Do not inject into moles, scars, birthmarks, bruises, rashes, or areas where the skin is hard, tender, red, damaged, burned, inflamed, or tattooed.
- If you need more than 1 injection for your dose, the injection sites should be at least 2 inches away from each other. The second injection site can be on the same part of the body or a different part of the body (See Figures I and J).
- For each injection, change (rotate) your injection sites. Choose an injection site that is at least 2 inches away from the injection site that you used for the last injection. It can be on the same part of the body or a different part of the body (See Figures I and J).
Figure J
Inject at least 2 inches apart
Step 9: Wash your hands well with soap and water before injecting Palynziq (See Figure K).
Figure K
Step 10: Clean the chosen site with an alcohol pad. Let the skin air dry for at least 10 seconds before injecting Palynziq (See Figure L).
- Do not touch the cleaned injection site.
- Do not remove the needle cap until you are ready to inject Palynziq.
Figure L
Inject Palynziq
Step 11: Hold the body of the prefilled syringe with 1 hand with the needle facing away from you (See Figure M).
- Do not use the prefilled syringe if it is dropped. Throw away the prefilled syringe if it is dropped and use a new prefilled syringe for your injection. See “Dispose of the used prefilled syringes” at the end of this Instructions for Use. Call BioMarin at 1‑866‑906‑6100 or your healthcare provider for help with Palynziq.
Figure M
Step 12: Pull the needle cap straight off the needle (See Figure N).
- Do not twist the needle cap during removal.
- Do not hold the prefilled syringe by the plunger or plunger head while taking the needle cap off.
- Before injecting Palynziq, check to make sure that the needle is not damaged or bent. Throw away the prefilled syringe if the needle is damaged or bent and use a new prefilled syringe for your injection. See
You may see a drop of liquid on the tip of the needle. This is normal.
Figure N
Step 13: Hold the body of the prefilled syringe in 1 hand between your thumb and index finger. Use your other hand to pinch up the skin around the injection site. Hold the skin firmly (See Figure O).
- Do not touch the plunger head while inserting the needle into the skin.
Figure O
Step 14: Use a quick motion to fully insert the needle into the pinched skin at a 45 to 90 degree angle (See Figure P).
Release the pinch of skin. Use that hand to hold the bottom of the prefilled syringe steady. Place the thumb of your other hand on the plunger head and place your index and middle fingers under the finger grips (See Figure P).
Figure P
Step 15: Use your thumb to push in the plunger slowly and steadily as far as it will go to inject all the medicine (See Figure Q). More pressure on the plunger may be needed to inject all the medicine for the 10 mg and 20 mg strength prefilled syringes.
Figure Q
Step 16: Slowly move your thumb up to release the plunger. The needle will automatically be covered by the prefilled syringe body (See Figure R).
Figure R
Treat injection site
Step 17: Treat injection site (if needed).
If you see drops of blood at the injection site, press a cotton ball or gauze over the injection site and hold for about 10 seconds. You may cover the injection site with a small adhesive bandage if needed.
If more than 1 prefilled syringe is needed for your prescribed dose:
Step 18: If your healthcare provider tells you to use more than 1 prefilled syringe for your prescribed dose, repeat Steps 4 to 17 listed above for each prefilled syringe that you use.
- Note: Do not give the injection in the same spot. The injection sites should be at least 2 inches away from each other. See Step 8 for information on choosing an injection site.
Dispose of the used prefilled syringes
Step 19: Put your used prefilled syringes in a puncture resistant container, such as an FDA‑cleared sharps disposal container immediately after use (See Figure S).
Do not throw away (dispose of) prefilled syringes in your household trash.
If you do not have an FDA-cleared sharps disposal container, you may use a household container that is:
- made of a heavy-duty plastic,
- can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out,
- upright and stable during use,
- leak-resistant, and
- properly labeled to warn of hazardous waste inside the container.
When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal and for specific information about sharps disposal in the state that you live in, go to the FDA’s website at:
Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container.
Note: Keep sharps disposal container out of the reach of children and pets.
Figure S
Storage of Palynziq
Figure T
- Store Palynziq in the refrigerator at 36°F to 46°F (2°C to 8°C) (See Figure T).
- If needed, you may store Palynziq at room temperature between 68°F to 77°F (20°C to 25°C) for up to 30 days.
- Write the date that you remove Palynziq from the refrigerator on the carton.
- If stored at room temperature, do not put Palynziq back in the refrigerator.
- Keep Palynziq in the original carton to protect from light.
- Do not freeze or shake Palynziq.
- Throw away Palynziq if it has been kept at room temperature for 30 days and has not been used, or after the expiration date on the carton, whichever comes first.
Keep Palynziq and all medicines out of the reach of children.
This Instructions for Use has been approved by the U.S. Food and Drug Administration.
Manufactured by:
BioMarin Pharmaceutical Inc.
Novato, CA 94949
U.S. License No. 1649
Revised: 10/2020
10PALYNZIQ - 2.5 MG/0.5 ML
NDC 68135-058-90
Palynziq
(pegvaliase-pqpz)
Injection
2.5 mg/0.5 mL
For Subcutaneous Use Only
Contains one x 2.5 mg/0.5 mL single-dose prefilled syringe.
Discard after use.
ATTENTION: Dispense the enclosed Medication Guide to each patient.
11PALYNZIQ - 10 MG/0.5ML
NDC 68135-756-20
Palynziq
(pegvaliase-pqpz)
Injection
10 mg/0.5 mL
For Subcutaneous Use Only
Contains one x 10 mg/0.5 mL single-dose prefilled syringe.
Discard after use.
ATTENTION: Dispense the enclosed Medication Guide to each patient.
12PALYNZIQ (SINGLE PACK) - 20 MG/ML
NDC 68135-673-40
Palynziq
(pegvaliase-pqpz)
Injection
20 mg/mL
For Subcutaneous Use Only
Contains one x 20 mg/mL single-dose prefilled syringe.
Discard after use.
ATTENTION: Dispense the enclosed Medication Guide to each patient.
13PALYNZIQ (MULTI-PACK) - 20 MG/ML
NDC 68135-673-45
Palynziq
(pegvaliase-pqpz)
Injection
20 mg/mL
For Subcutaneous Use Only
Contains ten 20 mg/mL single-dose prefilled syringes.
Discard after use.
ATTENTION: Dispense the enclosed Medication Guide to each patient.