What side effects are associated with this type of intervention?

Common side effects of Pegvaliase, an enzyme substitution therapy for Phenylketonuria, include injection site reactions, hypersensitivity reactions, and joint pain (arthralgia). Patients may also experience headache, fatigue, and gastrointestinal symptoms such as nausea. These side effects are typically manageable with appropriate medical supervision.

What prior FDA approvals exist?

Phenylketonuria (PKU) is primarily managed through dietary restrictions to limit phenylalanine intake. The FDA has approved several treatments for PKU, including sapropterin dihydrochloride (Kuvan), which enhances the activity of the residual phenylalanine hydroxylase enzyme. More recently, Pegvaliase (Palynziq) has been approved as an enzyme substitution therapy that breaks down phenylalanine, offering an alternative for patients who have difficulty managing their condition through diet alone. These treatments aim to reduce phenylalanine levels in the blood, thereby preventing the neurological damage associated with PKU.

What other types of research exist?

Promising novel alternatives to Pegvaliase for Phenylketonuria (PKU) patients include gene therapy approaches that aim to correct the underlying genetic defect, and small molecule drugs that either enhance residual enzyme activity or reduce phenylalanine absorption from the diet. These alternatives are currently under investigation and may offer new treatment options in the near future.

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Enzyme substitution therapy

Pegvaliase for Phenylketonuria (PEGASUS Trial)

Phase 3

Waitlist Available

Research Sponsored by BioMarin Pharmaceutical

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Diagnosis of PKU and failure to maintain recommended blood Phe levels on existing management (sapropterin dihydrochloride and Phe-restricted diet) demonstrated by 2 blood Phe concentration measurements > 600 μmol/L during the Screening/Run-in Period (7 to 10 days in between blood Phe assessments) and average blood Phe concentration > 600 μmol/L over the past 12 months (per available data).

Is 12 to 17 years old (US), inclusive, or 12 to 15 years (EU), inclusive, at the start of the Screening/Run-in Period (Day -28).

Must not have

A history of organ transplantation or on chronic immunosuppressive therapy.

Previous treatment with pegvaliase.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

Pivotal Trial

No Placebo-Only Group

Summary

This trial is testing pegvaliase injections in adolescents with PKU. The goal is to see if these injections are safe and effective. Pegvaliase helps the body break down a harmful substance that people with PKU cannot process on their own. Pegvaliase is a newer treatment for PKU, following earlier treatments like dietary restriction and sapropterin.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

While not explicitly listed here, common side effects of pegvaliase may include allergic reactions like anaphylaxis, joint pain, headaches, injection site reactions, and nausea. Participants should also be observed for symptoms after administration due to potential severe allergic responses.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have PKU and my blood Phe levels have been too high despite my current treatment.

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I am between 12 and 17 years old if in the US, or 12 to 15 if in the EU.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

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

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I have been treated with pegvaliase before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years for reporting.

Treatment Details

Side effects data

From 2021 Phase 3 trial • 37 Patients • NCT03694353

35%

Nasopharyngitis

32%

Headache

19%

Amino acid level decreased

19%

Oropharyngeal pain

19%

Influenza

16%

Pruritus

16%

Nausea

16%

Vomiting

16%

Arthralgia

16%

Cough

16%

Injection site bruising

14%

Limb injury

14%

Migraine

14%

Pain in extremity

14%

Seasonal allergy

14%

Fatigue

14%

Injection site induration

11%

Contusion

11%

Nasal congestion

11%

Diarrhoea

11%

Toothache

11%

Upper respiratory tract infection

11%

Injection site reaction

11%

Gastroenteritis

11%

Alopecia

11%

Urticaria

11%

Dizziness

Neck pain

Depression

Sinusitis

Rash

Helicobacter infection

Abdominal pain upper

Back pain

Pyrexia

Bronchitis

Gastrooesophageal reflux disease

Injection site pain

Paraesthesia

Sinus headache

Hypertension

Induration

Cellulitis

Conjunctivitis

Ear infection

Pneumonia

Anxiety

Sinus disorder

Paranasal sinus discomfort

Asthenia

Injection site pruritus

Hypoaesthesia

Ligament sprain

Dental caries

Musculoskeletal pain

Tinea pedis

Tooth abscess

Pharyngitis streptococcal

Gastroenteritis viral

Otitis media acute

Arthropod bite

Injection site erythema

Pain

Procedural pain

Gastric ulcer haemorrhage

Abortion spontaneous

COVID-19

Wound infection staphylococcal

Ectopic pregnancy

Anaphylactic reaction

Systemic inflammatory response syndrome

Cholecystitis

100%

80%

60%

40%

20%

Study treatment Arm

All Subjects

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: PegvaliaseExperimental Treatment1 Intervention

Group II: Drug: Diet OnlyExperimental Treatment1 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pegvaliase

2018

Completed Phase 3

~40

0 / 4Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Phenylketonuria (PKU) is managed mainly through dietary restriction of phenylalanine to prevent cognitive impairment and other complications. Pegvaliase, an enzyme substitution therapy, breaks down phenylalanine in the bloodstream, reducing its levels. This treatment is crucial for PKU patients as it provides an alternative to strict dietary management, potentially enhancing quality of life and adherence to treatment.

Progress in experimental phenylketonuria: a critical review.