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(S)-2-Amino-6-(2-Hydroxypropanoyl)-7,8-Dihydropteridin-4(3H)-One

This article discusses two clinical trials investigating the use of (S)-2-Amino-6-(2-Hydroxypropanoyl)-7,8-Dihydropteridin-4(3H)-One, also known as sepiapterin or PTC923, for the treatment of phenylketonuria (PKU). These Phase 3 studies aim to evaluate the efficacy, safety, and long-term effects of sepiapterin in patients with PKU, comparing it to existing treatments and assessing its impact on quality of life and dietary management.

Table of Contents

What is PTC923?

PTC923, also known as sepiapterin, is a new medication being developed to treat phenylketonuria (PKU). It is a synthetic form of a naturally occurring substance in the body called sepiapterin[1]. The chemical name for PTC923 is (S)-2-amino-6-(2-hydroxypropanoyl)-7,8-dihydropteridin-4(3H)-one. This medication is currently undergoing clinical trials to evaluate its effectiveness and safety in treating PKU.

What is Phenylketonuria?

Phenylketonuria (PKU) is a rare genetic disorder that affects the body’s ability to break down an amino acid called phenylalanine (Phe). In people with PKU, Phe builds up in the blood and can cause serious health problems, including brain damage, if left untreated. The main treatment for PKU involves following a strict low-protein diet to limit Phe intake[2].

How PTC923 Works

PTC923 (sepiapterin) is designed to help reduce blood Phe levels in people with PKU. It works by being converted in the body to a substance called tetrahydrobiopterin (BH4). BH4 is a cofactor that helps an enzyme called phenylalanine hydroxylase (PAH) break down Phe. In people with PKU, the PAH enzyme doesn’t work properly, leading to a buildup of Phe. By providing more BH4, PTC923 aims to help the body process Phe more effectively[1][2].

Clinical Trials of PTC923

PTC923 is currently being studied in clinical trials to evaluate its effectiveness and safety in treating PKU. Two main studies are underway:

  1. A Phase 3 study comparing PTC923 (sepiapterin) to sapropterin (another PKU treatment) in patients aged 2 years and older[1].
  2. A long-term Phase 3 open-label study to evaluate the safety and effectiveness of PTC923 in patients of all ages with PKU[2].

These studies aim to determine how well PTC923 reduces blood Phe levels compared to existing treatments and assess its long-term safety and tolerability.

Dosage and Administration

PTC923 is being studied as a powder for oral use. In the clinical trials, the maximum daily dose being tested is 60 mg/kg (milligrams per kilogram of body weight)[1][2]. The exact dosing regimen will be determined based on the results of the clinical trials. Patients will need to mix the powder with a liquid or food before taking it.

Safety and Side Effects

One of the main goals of the ongoing clinical trials is to evaluate the safety and tolerability of PTC923. The long-term study is specifically designed to assess any side effects that may occur with extended use of the medication[2]. Common side effects and any potential risks will be better understood once the trial results are available.

It’s important to note that people with moderate to severe kidney problems (a glomerular filtration rate less than 60 mL/min) are not eligible for the current clinical trials, suggesting that kidney function may be a consideration for this medication[1].

Quality of Life Impact

The clinical trials are also assessing how PTC923 affects the quality of life of people with PKU. This is being measured using specific questionnaires designed for different age groups, including children, adolescents, and adults with PKU[2]. These assessments will help determine if PTC923 improves overall well-being and daily functioning for people living with PKU.

Conclusion

PTC923 (sepiapterin) represents a potential new treatment option for people with phenylketonuria. By helping the body process phenylalanine more effectively, it may allow for better management of PKU and potentially improve quality of life. However, as the medication is still in clinical trials, more research is needed to fully understand its effectiveness, safety, and long-term impacts. Patients with PKU should consult with their healthcare providers about the potential benefits and risks of participating in clinical trials or using this medication once it becomes available.

Aspect Study 1 (2023-506238-61-00) Study 2 (2023-509229-31-00)
Study Type Phase 3, Randomized, Crossover, Open-Label, Active-Controlled Phase 3, Open-Label
Primary Objective Compare efficacy of sepiapterin to sapropterin in reducing blood Phe levels Evaluate long-term safety of PTC923 and changes in dietary Phe/protein consumption
Key Inclusion Criteria Age ≥2 years, blood Phe level ≥360 μmol/L Any age, clinical diagnosis of PKU with HPA
Primary Endpoints Mean change in blood Phe levels from baseline Safety assessment and change in dietary Phe/protein consumption
Treatment Duration Up to 6 weeks Up to 24 months
Dosage Up to 60 mg/kg daily Up to 60 mg/kg daily

FAQ

  • What is phenylketonuria (PKU)? Phenylketonuria (PKU) is a genetic metabolic disorder characterized by the body's inability to properly process the amino acid phenylalanine. This can lead to a buildup of phenylalanine in the blood, which can cause serious health problems if left untreated.
  • What is the main purpose of these clinical trials? The main purpose of these clinical trials is to evaluate the effectiveness and safety of sepiapterin (PTC923) in treating phenylketonuria. They aim to compare it with existing treatments and assess its long-term effects on patients with PKU.
  • Who can participate in these clinical trials? Participants in these trials include males and females of various ages with a clinical diagnosis of PKU. Specific inclusion criteria may vary between the two studies, but generally, participants must have documented high blood phenylalanine levels and be willing to comply with study procedures.
  • What are the primary outcomes being measured in these trials? The primary outcomes include changes in blood phenylalanine levels, safety assessments through monitoring adverse events, and changes in dietary phenylalanine/protein consumption. The long-term study also focuses on the safety of extended treatment with PTC923.
  • How long do these clinical trials last? The duration of the trials varies. The comparative study lasts for several weeks, while the long-term safety study can last up to 24 months. This allows researchers to assess both short-term efficacy and long-term safety of the treatment.

Ongoing Clinical Trials on (S)-2-Amino-6-(2-Hydroxypropanoyl)-7,8-Dihydropteridin-4(3H)-One

  • Study on the Long-Term Safety of PTC923 (Sepiapterin) for Patients with Phenylketonuria

    Not recruiting

    3 1 1
    Investigated drugs:
    Czechia Denmark France Germany Italy The Netherlands +4

  • Study Comparing Sepiapterin and Sapropterin for Treating Phenylketonuria in Patients Aged 2 Years and Older

    Not recruiting

    3 1 1 1
    Investigated drugs:
    Czechia Denmark France Germany Italy The Netherlands +3

Glossary

  • Phenylketonuria (PKU): A genetic disorder that affects the body's ability to process the amino acid phenylalanine, leading to its buildup in the blood and potential health problems if untreated.
  • Sepiapterin (PTC923): The investigational drug being studied in these clinical trials, chemically known as (S)-2-Amino-6-(2-Hydroxypropanoyl)-7,8-Dihydropteridin-4(3H)-One.
  • Phenylalanine (Phe): An essential amino acid that cannot be properly metabolized in people with PKU, leading to its accumulation in the blood.
  • Sapropterin: An existing treatment for PKU that is being compared to sepiapterin in one of the clinical trials.
  • Tetrahydrobiopterin (BH4): A naturally occurring enzyme cofactor involved in the metabolism of phenylalanine.
  • Pharmacokinetics (PK): The study of how a drug is absorbed, distributed, metabolized, and eliminated by the body.
  • Glomerular Filtration Rate (GFR): A measure of kidney function used to assess eligibility for the clinical trials.
  • Quality of Life (QOL): A measure of an individual's overall well-being and life satisfaction, which is being assessed in these trials using specific questionnaires.

References

  1. http://clinicaltrials.eu/trial/study-comparing-sepiapterin-and-sapropterin-for-treating-phenylketonuria-in-patients-aged-2-years-and-older/
  2. http://clinicaltrials.eu/trial/study-on-the-long-term-safety-of-ptc923-sepiapterin-for-patients-with-phenylketonuria/