Pegvaliase-pqpz Approved by FDA for Adolescents With Phenylketonuria

The FDA has approved pegvaliase-pqpz (Palynziq; BioMarin Pharmaceutical) for adolescents aged 12 years and older with phenylketonuria (PKU) who have uncontrolled blood phenylalanine (Phe) concentrations greater than 600 micromoles per liter (µmol/L). The approval makes pegvaliase the only enzyme substitution therapy available for both adults and adolescents with this inherited metabolic disorder.¹

Pivotal Results From PEGASUS Bolster Pegvaliase to Approval

Regulatory approval was based on results from PEGASUS, a phase 3 multicenter, open-label, randomized controlled trial evaluating pegvaliase compared with diet alone in 55 adolescents aged 12 to 17 years with PKU. Participants were randomized 2:1 to receive pegvaliase (n = 36) or diet-only management (n = 19).^1,2

At 72 weeks, pegvaliase demonstrated statistically significant reductions in blood Phe levels compared with diet alone. The pegvaliase group showed a mean reduction of 473 µmol/L from a baseline of 1,025 µmol/L, compared with only a 19 µmol/L reduction in the diet-only group. This represented a treatment difference of 409 µmol/L (95% CI, −579 µmol/L to −240 µmol/L).^1,2

Nearly half of participants (44.4%) achieved blood Phe levels below guideline recommendations by the end of the 72-week treatment phase. Among this group, 75% reached levels below 120 µmol/L, with an average Phe reduction of 828 µmol/L, representing a 94% decrease from baseline.¹

Nine participants who achieved blood Phe levels below 30 µmol/L were able to increase their intact protein intake by an average of 318% from baseline while decreasing medical food protein intake by 55%. Six individuals discontinued medical food completely, according to the PEGASUS investigators.¹

Safety Profile and REMS Considerations

The safety profile in adolescents was consistent with findings from adult studies. The most common adverse reactions occurring in at least 20% of adolescent patients included injection site reactions, arthralgia, headache, pyrexia, hypersensitivity reactions, dizziness, nausea, vomiting, fatigue, and pain in extremities.¹

Two patients (6%) discontinued treatment due to adverse reactions. This discontinuation rate was notably lower than rates observed in adult trials, where 15% of patients discontinued due to adverse events.¹

Anaphylaxis occurred in 4 of 36 (11%) pegvaliase-treated adolescent patients, with each experiencing 1 episode. Most adverse reactions occurred during the induction and titration phase, with frequency decreasing during maintenance therapy. Given the risk of anaphylaxis, pegvaliase carries a boxed warning, and it is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS).¹

Accordingly, all patients must be prescribed auto-injectable epinephrine prior to therapy initiation. Furthermore, the initial dose of pegvaliase must be administered under the supervision of a health care provider who is equipped to manage anaphylaxis, with at least 60 minutes of observation following injection.¹

Pharmacist Implications

Adolescence represents a particularly vulnerable period for individuals with PKU. Dietary control of Phe during childhood can prevent major developmental neurological consequences, but poor Phe control during adolescence and adulthood is associated with neuropsychological deficits and functional impairment, with elevated Phe levels during adolescence negatively impacting attention, executive functions, and attentional performance. Pegvaliase presents as a new option to reduce blood Phe levels in patients with PKU and could revolutionize treatment outcomes for this population.^3,4

Pharmacists play critical roles in supporting adolescents initiating pegvaliase therapy. Key responsibilities include verifying REMS certification and enrollment before dispensing, ensuring patients have valid epinephrine prescriptions and understand proper use, providing education on injection technique and site rotation to minimize injection site reactions, counseling on recognition and management of hypersensitivity reactions, and coordinating with prescribers to monitor blood Phe levels and adjust dosing.

The medication requires weekly subcutaneous injections with dose titration over several months. Blood Phe monitoring should occur every 4 weeks until a maintenance dose is established, with periodic monitoring continuing during maintenance therapy.¹

Pharmacists should emphasize that dietary protein and Phe intake must be monitored and adjusted based on blood Phe levels throughout treatment. For adolescents achieving very low Phe levels (below 30 µmol/L), increasing intact protein intake while decreasing medical food consumption may be appropriate under medical supervision.

REFERENCES

1. U.S. Food and Drug Administration approves BioMarin’s PALYNZIQ (pegvaliase-pqpz) for adolescents 12 years of age and older with phenylketonuria (PKU). News release. BioMarin Pharmaceutical. Released February 27, 2026. Accessed March 2, 2026. https://www.prnewswire.com/news-releases/us-food-and-drug-administration-approves-biomarins-palynziq-pegvaliase-pqpz-for-adolescents-12-years-of-age-and-older-with-phenylketonuria-pku-302700090.html

2. BioMarin Pharma’s phase 3 PEGASUS trial evaluating Palynziq in adolescents with phenylketonuria meets primary efficacy endpoint. News release. BioMarin Pharmaceutical. Released April 3, 2025. Accessed March 2, 2026. https://www.pharmabiz.com/NewsDetails.aspx?aid=177164&sid=2#:~:text=BioMarin%20Pharma's%20phase%203%20PEGASUS,phenylketonuria%20meets%20primary%20efficacy%20endpoint

3. National PKU Alliance. About PKU. Accessed March 2, 2026. https://www.npkua.org/Education/About-PKU

4. Câmara B, Florindo C, Bandeira de Lima C, et al. Rethinking phenylalanine levels in phenylketonuria for optimal neurocognitive development beyond childhood. Front Pediatric–Pediatric Immunol. 2025;13:1488809. doi:10.3389/fped.2025.1488809