Rapid Drug Desensitization Study in Adults Experiencing Hypersensitivity Reactions to Palynziq

Inclusion Criteria:

• Age:

1.Participants must be 18 years of age or older inclusive, at the time of signingthe informed consent.

• Type of Participant and Disease Characteristics 2. Participants must havephenylketonuria and must have been receiving commercial Palynziq and enrolled in theREMS.

3. Participants must have developed HSRs leading to treatment interruption orreduction of dose or dosing frequency (Graade 2 or above) while on Palynziq,and must be able to undergo RDD within 6weeks from the reactive HSR and lastPalynziq dose.

• Sex and Contraceptive/Barrier Requirement 4. Males and females are eligible toparticipate in this clinical study. Contraceptive use is not required during thestudy. Please refer to the Pregnancy section of USPI for further information.

• Informed Consent 5. Participants must be capable of giving written informed consentas described in Section 10.1, which includes compliance with the requirements andrestrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria:

• Medical Conditions:

1. Participant may not have any kind of disorders that, in the opinion of theinvestigator, may compromise the ability of the participant to give writteninformed consent and/or comply with any aspect of the study, and/or where anyaspect of participation would be medically inadvisable for the underlyingdisorder.

2. Participant must not be pregnant on the day of the RDD.

3. Participants with uncontrolled asthma, active upper repiratory infection orother active infections, or cardiovascular disease. Asthma control will beassessed using the Asthma Control Test at screening.

• Prior/Concomitant Therapies:

4. Participants were not using antihistamine premedication(s) at the time ofreactive HSRs.

5. Participants are willing and able to resume and tolerate Palynziq at thereactive dose prior to the RDD.

6. Participant must not be receiving concurrent injectables containing PEG withthe exception of PEG-containing vaccines, such as COVID-19 vaccinations (seeSection 6.7).

7.Participants receiving beta blockers.

• Prior/Concurrent Clinical Study Experience 8. Participants may not be currentlyparticipating in an interventional study of any investigational product, device, orprocedure, or any other BioMarin clinical trial or post-marketing study.

Other Exclusions 9. Participants must not be experiencing reactions that are not appropriate for RDD, including severe cutaneous adverse reactions (SCAR) as defined by the American Academy for Allergy, Asthma, and Immunology.