Recognizing how the immune system responds to PALYNZIQ is critical to understanding the safety, dosing, and efficacy
As with all therapeutic proteins, there is potential for immunogenicity1


Non–IgE-mediated anaphylaxis was observed in PALYNZIQ clinical trials1,a


Anaphylaxis has been reported after administration of PALYNZIQ and may occur at any time during treatment1
- Most episodes occurred within 1 hour after injection
(81%; 34 of 42 episodes) , though delayed episodes also occurred up to48 hours after administration of PALYNZIQ1 - Most episodes occurred within 1 year of dosing
(69%; 29 of 42 episodes) , but cases also occurred after 1 year of dosing and up to 1604 days (4.4 years) of total follow-up1 - 48% of anaphylaxis episodes
(20 of 42 episodes) were managed with administration of auto-injectable epinephrine1 - Consider having an adult observer for patients who may need assistance in recognizing and managing anaphylaxis1
a27 of 29 patients who had anaphylaxis were tested for anti–pegvaliase-pqpz IgE antibodies, which recognize the PEGylated protein product. Of those 27 patients, 26 tested negative. The one patient who screened positive for anti–pegvaliase-pqpz IgE had insufficient sample to confirm IgE positivity. This patient tested negative for anti–pegvaliase-pqpz IgE at routine visits before and after the anaphylaxis episode.1
Learn about the different types of hypersensitivity 

Type I vs Type III hypersensitivity


In the clinical trials, the majority of adverse reactions were mild to moderate in severity1,2
Most common adverse reactions (≥15% in an induction/titration/maintenance regimen) in clinical trials1


- 15% of
patients (44 of 285) discontinued treatment due to an adverse event1 - The most common adverse reactions leading to discontinuation were hypersensitivity reactions (6%), including anaphylaxis (3%), angioedema (1%), arthralgia (4%), generalized skin reactions lasting at least 14 days (2%), and ISRs (1%)1
View adverse reactions by exposure-adjusted rate 

The exposure-adjusted rate of adverse reactions was highest during induction and titration, and generally decreased in the maintenance phase1
Adverse reactions by exposure-adjusted rate1


cHypersensitivity, including anaphylaxis.
- The exposure-adjusted rate represents the number of episodes divided by person-years (the number of patients multiplied by the years patients were exposed to treatment)
- It is calculated by taking the number of events divided by the number of person-years (the number of patients multiplied by the number of years they were exposed to the treatment)
Rates of the 3 most common adverse reactions decreased from induction/titration to maintenance,d despite increasing dose1,6
Comparison of exposure adjusted AE rates in induction/titration vs maintenance phases1,6


cHypersensitivity, including anaphylaxis.
dMaintenance phase defined as when subjects reached stable dose for 8 weeks.
eHypersensitivity, including anaphylaxis.
fMaintenance, all doses includes patients on placebo and PALYNZIQ doses
The types and rate of adverse reactions reported during the maintenance phase were similar in patients who received 20 mg, 40 mg, and 60 mg once daily.1
- The exposure-adjusted rate of anaphylaxis was highest during induction and titration phases (0.25 episodes/person-years) and decreased in the maintenance phase (0.05 episodes/person-years)
- The frequency of hypersensitivity reactions with PALYNZIQ is highest early in treatment when the immune response is most reactive, but may occur at any time during treatment1
- Later in treatment, the immune response stabilizes1,3
- The exposure-adjusted rate represents the number of episodes divided by person-years (the number of patients multiplied by the years patients were exposed to treatment)
- It is calculated by taking the number of events divided by the number of person-years (the number of patients multiplied by the number of years they were exposed to the treatment)
In clinical trials, adverse reactions were managed with medication, dose reduction, interruption, and discontinuation1

- Premedication1,7
Premedication may be considered, based on individual patient tolerability, prior to each dose of PALYNZIQ. Most frequently administered H1- and H2-receptor antagonists and antipyretics during PRISM-2g,h,i,j:- ranitidine hydrochloridej
- ibuprofen
- fexofenadine hydrochloride
- cetirizine hydrochloride
- diphenhydramine hydrochloride
- loratadine
- acetaminophen
- naproxen sodium

- Anaphylaxis1
- Medication: managed with autoinjectable epinephrine, corticosteroids, antihistamines, and/or oxygen
- Interruption: 4% of patients
- Discontinuation: 3% of patients

- Arthralgia1
- Medication: managed with nonsteroidal anti-inflammatory drugs, glucocorticoids, and acetaminophen
- Dose reduction: 15% of patients
- Interruption: 13% of patients
- Discontinuation: 4% of patients

- Injection site reactions1
- Medication: treated with topical antihistamine, corticosteroids
- Dose reduction: 4% of patients
- Interruption: 4% of patients
- Discontinuation: 1% of patients
gPatients (n=215) may have been prescribed premedications in combination, and/or may have switched between different premedication regimens during the study period.
hThe rates of use of these medications in this population only partially reflects their use as premedications; these medications may also have been used to treat other conditions, such as seasonal allergies, headaches, etc.
iDuring PRISM-2, premedication was administered 2-3 hours prior to PALYNZIQ.
jPlease note: the FDA has advised a voluntary recall of ranitidine made by many manufacturers, due to concerns over purity. Consider substituting a different H2 blocker.
References: 1. PALYNZIQ [package insert]. Novato, CA: BioMarin Pharmaceutical Inc; 2020. 2. Thomas J, Levy H, Amato S, et al, for the PRISM investigators. Pegvaliase for the treatment of phenylketonuria: results of a long-term phase 3 clinical trial program (PRISM). Mol Genet Metab. 2018;124(1):27-38. 3. Gupta S, Lau K, Harding CO, et al. Association of immune response with efficacy and safety outcomes in adults with phenylketonuria administered pegvaliase in phase 3 clinical trials. EBioMedicine. 2018;37:366-373. 4. Montañez MI, Mayorga C, Bogas G, et al. Epidemiology, mechanisms, and diagnosis of drug-induced anaphylaxis. Front Immunol. 2017;8:1-10. 5. Hausmann O, Daha M, Longo N, et al. Pegvaliase: immunological profile and recommendations for the clinical management of hypersensitivity reactions in patients with phenylketonuria treated with this enzyme substitution therapy. Mol Genet Metab. 2019;128(1-2):84-91. doi:10.1016/j.ymgme.2019.05.006. 6. Data on file, BioMarin Pharmaceutical Inc; 2017.