Researchers tested a new medicine called sepiapterin to help people with phenylketonuria (PKU), a rare condition where the body can’t process a protein building block called phenylalanine. In this study, 169 people took sepiapterin daily for up to 18 months. The results showed that people could safely eat about 2.3 times more protein-containing foods than before, while keeping their blood phenylalanine levels safe. The medicine was generally well-tolerated with few side effects, suggesting it could give people with PKU more food choices and better quality of life.

The Quick Take

  • What they studied: Whether a new medicine called sepiapterin could help people with PKU safely eat more foods containing protein without their blood phenylalanine levels becoming dangerous.
  • Who participated: 169 people ranging from babies (0.2 years old) to adults (55 years old) with phenylketonuria who were taking sepiapterin. About 102 of these people participated in the detailed food tolerance testing part of the study.
  • Key finding: People taking sepiapterin were able to increase their daily protein intake from about 28 mg per kilogram of body weight to about 63 mg per kilogram—more than doubling their dietary protein allowance—while maintaining safe blood phenylalanine levels.
  • What it means for you: If you or a loved one has PKU, this medicine may allow you to eat a wider variety of normal foods instead of following such a strict diet. However, this is interim data, and you should discuss with your doctor whether this treatment is appropriate for your specific situation.

The Research Details

This was an ongoing Phase 3 clinical trial, which is the final stage of testing before a medicine can be approved. Participants received sepiapterin as a daily oral dose adjusted for their age and weight. After 2 weeks, those whose blood phenylalanine levels were safely controlled (below 360 μmol/L) entered a 26-week period where researchers gradually increased their dietary protein intake while carefully monitoring their blood phenylalanine levels. Other participants continued treatment and could choose to eat less restrictively without formal testing.

The researchers measured two main things: how much dietary protein people could eat while staying safe, and what side effects occurred. They tracked these measurements from the start of treatment through 26 weeks of dietary adjustment.

This study design is important because it shows real-world results over a long time period (median of 72.9 weeks of treatment). By carefully monitoring people while gradually increasing their protein intake, researchers could determine exactly how much dietary freedom sepiapterin provides. This approach is more meaningful than just measuring blood levels—it shows whether the medicine actually improves people’s daily lives.

This is interim data from an ongoing study, meaning the results are based on data collected through September 2024, but the study is still continuing. The study included a diverse age range (infants to adults), which strengthens the findings. However, because this is an open-label study (everyone knew they were receiving sepiapterin), there’s no comparison group to rule out placebo effects. The relatively low rate of treatment discontinuation (1.8%) suggests the medicine was generally well-tolerated.

What the Results Show

The main finding was that people could significantly increase their protein intake while taking sepiapterin. At the start of the study, participants were eating an average of 27.6 mg of dietary phenylalanine per kilogram of body weight daily. After 26 weeks of treatment and dietary adjustment, this increased to 62.5 mg per kilogram per day—an increase of about 36.4 mg per kilogram daily. This difference was statistically significant (P<0.0001), meaning it’s very unlikely to have occurred by chance.

To put this in perspective, this means a person could go from eating very limited protein sources to eating a much more normal diet with greater variety. For example, someone might be able to eat more chicken, eggs, dairy products, and other protein-rich foods that are typically restricted in PKU diets.

The safety profile was also encouraging. Among the 169 participants, 29% experienced some treatment-related side effects, but these were generally mild. Only 3 people (1.8%) stopped taking the medicine because of side effects, and there were no serious side effects or deaths related to the treatment.

The study tracked treatment-related side effects in detail. While 29% of participants experienced some adverse events, the vast majority were mild and manageable. No serious adverse events were attributed to sepiapterin treatment. The fact that 98.2% of participants continued treatment suggests the medicine was acceptable to most people taking it. The study also showed that the medicine’s benefits were maintained over the long term, with a median treatment duration of 72.9 weeks.

Phenylketonuria has traditionally required strict dietary management from infancy, with people limiting protein intake to prevent dangerous blood phenylalanine levels. Previous treatments have had limited success in allowing dietary liberalization. This sepiapterin study shows more promising results than earlier approaches, suggesting it may represent a meaningful advance in PKU management. However, more research is needed to compare sepiapterin directly with other emerging PKU treatments.

This is interim data from an ongoing study, so the final results may differ. The study was open-label, meaning everyone knew they were receiving sepiapterin, which could influence how side effects are reported or how strictly people followed dietary recommendations. The study didn’t include a control group (people receiving a placebo or standard treatment), making it harder to determine how much benefit comes specifically from sepiapterin versus other factors. Additionally, the study population included a wide age range, so results may vary for different age groups. Long-term safety data beyond the current follow-up period is not yet available.

The Bottom Line

Based on this interim evidence, sepiapterin appears to be a promising treatment option for people with phenylketonuria who want to expand their dietary choices. The evidence suggests moderate to strong confidence in its ability to increase dietary protein tolerance while maintaining safety. However, this should only be considered under close medical supervision with regular blood phenylalanine monitoring. Discuss with your PKU specialist whether sepiapterin is appropriate for your situation, as individual responses may vary.

This research is most relevant for people with phenylketonuria of any age who are struggling with the restrictions of a PKU diet. It may be particularly important for adolescents and adults who want more dietary freedom and better quality of life. Parents of children with PKU should discuss this option with their metabolic specialists. People without PKU do not need to take action based on this research.

Based on this study, people taking sepiapterin showed improved dietary tolerance within 26 weeks. However, the initial 2-week period is important for determining if the medicine is working well enough to proceed with dietary adjustments. Full benefits may take several months to realize as diet is gradually liberalized. Long-term maintenance of these benefits appears stable based on the 72.9-week median follow-up, but continued monitoring is essential.

Want to Apply This Research?

  • Track daily dietary phenylalanine intake in grams and weekly blood phenylalanine levels (in μmol/L or mg/dL). This allows users to see the correlation between diet changes and blood levels, helping them understand their personal tolerance threshold.
  • Users can use the app to gradually increase protein-containing foods while monitoring blood phenylalanine levels. The app could provide a structured meal plan that slowly expands food choices week by week, with reminders to check blood levels at recommended intervals.
  • Implement a dashboard showing: (1) current dietary phenylalanine intake vs. personal safe limit, (2) trend graph of blood phenylalanine levels over time, (3) list of newly-tolerated foods added to diet, and (4) appointment reminders for metabolic clinic visits and blood work. This creates accountability and helps users and their doctors track progress.

This research describes interim results from an ongoing clinical trial. Sepiapterin is a prescription medication that should only be used under the supervision of a physician specializing in metabolic disorders. The findings presented here are not a substitute for professional medical advice. If you or a loved one has phenylketonuria, discuss these results with your metabolic specialist or genetic counselor to determine if sepiapterin is appropriate for your individual situation. Do not start, stop, or change any PKU treatment without consulting your healthcare provider. Blood phenylalanine levels must be monitored regularly during any treatment changes.