Pegvaliase for Phenylketonuria

(PEGASUS Trial)

Not currently recruiting at 21 trial locations

Overseen By Trial Specialist

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: BioMarin Pharmaceutical

Must not be taking: PKU treatments, PEG injectables

Disqualifiers: Organ transplant, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 72 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and effectiveness of pegvaliase injections for treating phenylketonuria (PKU), a genetic condition that prevents the body from breaking down a certain amino acid, resulting in high blood levels. Participants will either follow a diet alone or start with the diet and later receive pegvaliase. The trial targets adolescents aged 12 to 17 with PKU who struggle to maintain stable blood levels with current treatments. As a Phase 3 trial, it represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment for PKU.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you must stop any PKU treatments and certain injectable drugs before starting the study. If you're on medication for ADHD, depression, or other psychiatric disorders, you can continue as long as the dose is stable.

Is there any evidence suggesting that pegvaliase is likely to be safe for humans?

Research has shown that pegvaliase, a treatment for phenylketonuria (PKU), has produced varying safety results in past studies. Some studies found that patients' safety improved over time with ongoing treatment. However, serious risks exist, including anaphylaxis (a severe allergic reaction) and other side effects.

The safety results generally aligned with researchers' expectations from the start to the later stages of treatment. Pegvaliase has been used in adults with PKU, providing insights into expected safety outcomes.

While these findings offer some reassurance, they also highlight the need to monitor for serious side effects. Prospective trial participants should discuss these findings with their healthcare provider to make an informed decision. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for PKU?

Unlike the standard dietary management for phenylketonuria (PKU), pegvaliase offers a unique approach by using an enzyme therapy to target and break down phenylalanine directly. This is exciting because it provides a direct biochemical solution, potentially reducing the need for strict dietary restrictions that can be challenging for patients to maintain. Researchers are hopeful that pegvaliase will offer more freedom and improved quality of life for those with PKU, setting it apart from current dietary management strategies.

What evidence suggests that pegvaliase might be an effective treatment for PKU?

Research has shown that pegvaliase, which participants in this trial may receive, can effectively lower blood phenylalanine (Phe) levels in people with phenylketonuria (PKU). One study found that teenagers treated with pegvaliase experienced an average drop of 49.7% in their blood Phe levels. This decrease was both significant for health and proven to be more effective than a placebo. Additionally, pegvaliase has been more successful in reducing Phe levels than sapropterin or a special diet alone over one to two years. These findings suggest that pegvaliase can greatly aid in managing PKU by lowering harmful Phe levels in the blood. Meanwhile, participants in the diet-only arm of this trial will manage their PKU with diet alone before starting pegvaliase treatment at a later stage. ^{1 6 7 8 9}

Who Is on the Research Team?

Study Director

Principal Investigator

BioMarin Pharmaceutical

Are You a Good Fit for This Trial?

This trial is for adolescents aged 12-17 in the US (or 12-15 in the EU) with Phenylketonuria (PKU) who haven't been able to control their blood Phe levels through current treatments. They must be stable on any psychiatric meds, willing to follow a diet plan, and have an adult supervisor during treatment. Sexually active participants need to use two forms of contraception.

Inclusion Criteria

I am using two forms of birth control and do not plan to get pregnant or father a child while in the study.

I've been on a stable dose of my psychiatric medication for at least 8 weeks and can keep it steady.

I am able to understand and sign the consent form.

Exclusion Criteria

Your creatinine levels in your blood are higher than 1.5 times the normal upper limit.

I haven't used any PEG-containing injectable drugs recently, except for COVID-19 vaccines.

I have had an organ transplant or am on long-term immune-weakening medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily pegvaliase injections or manage PKU with diet alone

72 weeks

Crossover Treatment

Participants in the diet-only control arm initiate pegvaliase treatment

143 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Pegvaliase

Trial Overview The study tests Pegvaliase injections against a diet-only approach in managing PKU. It's an open-label Phase 3 trial where about 54 young people are randomly assigned to either get the drug or stick with dietary management to see which is safer and works better.

How Is the Trial Designed?

Group I: Pegvaliase Experimental Treatment 1 Intervention

Group II: Diet Only Experimental Treatment 1 Intervention

Participants will be managing their PKU with diet alone. Participants in the diet-only control arm will be required to maintain and adjust dietary and medical protein food intake through Week 72, initiating pegvaliase treatment beginning Week 73 and, from Weeks 73 through 215.

Who Is Running the Clinical Trial?

BioMarin Pharmaceutical

Lead Sponsor

Trials

162

Recruited

115,000+

Alexander Hardy

BioMarin Pharmaceutical

Chief Executive Officer since 2023

MBA from INSEAD

Greg Friberg

BioMarin Pharmaceutical

Chief Medical Officer

MD from New York Medical College

Published Research Related to This Trial

Pegvaliase, an injectable enzyme therapy for phenylketonuria (PKU), can cause Type III hypersensitivity reactions, particularly during the initial induction and titration phases, but these reactions tend to decrease over time with continued treatment due to factors like antibody affinity maturation.

To manage hypersensitivity adverse events (HAEs) effectively, it is recommended to use a slow induction and titration regimen, premedication with H1-receptor antagonists, and to ensure patients carry auto-injectable adrenaline, which can improve tolerability and safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegvaliase: Immunological profile and recommendations for the clinical management of hypersensitivity reactions in patients with phenylketonuria treated with this enzyme substitution therapy. Hausmann, O., Daha, M., Longo, N., et al.[2020]

Citations

1. biomarin.com biomarin.com/news/press-releases/biomarin-announces-positive-pivotal-phase-3-data-for-palynziq-pegvaliase-pqpz-in-adolescents-with-phenylketonuria-at-15th-international-congress-of-inborn-errors-of-metabolism-2/

BioMarin Announces Positive Pivotal Phase 3 Data for ... New data from Phase 3 PEGASUS study demonstrates a 49.7% decrease in mean blood Phe levels in adolescents aged 12-17 treated with PALYNZIQ.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11061743/

Pegvaliase for the treatment of phenylketonuria Pegvaliase led to mean blood Phe reductions that were clinically meaningful and statistically significant versus placebo [13] and sustained on a population ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1096719223007448

Long-term comparative effectiveness of pegvaliase versus ... Pegvaliase was more effective at lowering mean blood Phe levels than sapropterin + MNT or MNT alone at 1 and 2 years of treatment.

4. prnewswire.com prnewswire.com/news-releases/biomarin-announces-positive-pivotal-phase-3-data-for-palynziq-pegvaliase-pqpz-in-adolescents-with-phenylketonuria-at-15th-international-congress-of-inborn-errors-of-metabolism-302547986.html

BioMarin Announces Positive Pivotal Phase 3 Data for ... New data from Phase 3 PEGASUS study demonstrates a 49.7% decrease in mean blood Phe levels in adolescents aged 12-17 treated with PALYNZIQ.

5. checkrare.com checkrare.com/results-from-the-pegasus-clinical-trial-of-pegvaliase-in-patients-with-pku/

Results From the PEGASUS Clinical Trial of Pegvaliase in ... Results from the study show the ability of pegvaliase to significantly lower Phe compared to diet alone. At baseline, mean blood Phe was 1026.4 ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S109671922300327X

Two-year interim safety and efficacy of pegvaliase in ... Here we report the primary endpoint, change in blood Phe levels from baseline to Week 52, and 2-year interim efficacy and safety results (to Week 144; data cut- ...

7. medical.biomarin.com medical.biomarin.com/en-us/wp-content/uploads/sites/2/2023/07/60mg-palynziq-long-term-safety-and-efficacy.pdf?v=1.0

The long-term safety and efficacy of pegvaliase 60 mg/day in ... The long-term safety and efficacy of pegvaliase 60 mg/day in adults with phenylketonuria ... for ≥4 weeks with ≥80% adherence, and safety data are.

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40094206/

Pegvaliase therapy for phenylketonuria: Real-world safety ... Pegvaliase effectively reduced Phe levels in PKU patients, although it carried significant risks of anaphylaxis and other adverse events.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT05270837

Study to Evaluate the Safety and Efficacy of Pegvaliase in ... This Phase 3 multicenter study is designed to evaluate the safety and efficacy of pegvaliase administered daily to adolescents (ages 12 to 17 years old (US), ...