Sepiapterin

SEPHIENCE is a precursor of the enzymatic co-factor tetrahydrobiopterin (BH 4 ) which activates PAH.

• SEPHIENCE is indicated for the treatment of hyperphenylalaninemia (HPA) in adult and pediatric patients 1 month of age and older with sepiapterin-responsive phenylketonuria (PKU). SEPHIENCE is to be used in conjunction with a phenylalanine (Phe)-restricted diet.

• None. None.contraindicated

Patients treated with SEPHIENCE should be on a dietary protein and a Phe-restricted diet. ( 2.1 ) Administer SEPHIENCE orally once daily with food. ( 2.2 ) The recommended starting dosage of SEPHIENCE is: ( 2.2 ) Age SEPHIENCE (mg/kg) per day Less than 6 months 7.5 mg/kg 6 months to less than 1 year 15 mg/kg 1 year to less than 2 years 30 mg/kg 2 years and older 60 mg/kg Important Administration Information: prepare SEPHIENCE calculated daily doses of < 1,000 mg as a liquid mixture (25 mg/mL), and administer exact prescribed dose volume (mL). ( 2.2 , 2.3 ) See full prescribing information for complete preparation and administration instructions. ( 2.3 ) 2.1 Important Recommendation Prior to SEPHIENCE Treatment Treatment with SEPHIENCE should be directed by physicians knowledgeable in the management of PKU. Biochemical response to SEPHIENCE treatment cannot generally be pre-determined by laboratory testing (e.g., molecular testing), and should be determined through a therapeutic evaluation of SEPHIENCE [see Dosage and Administration ( 2.2 ) and Clinical Studies ( 14.1 )]. Obtain baseline blood Phe concentration before initiating treatment. All patients with PKU who are treated with SEPHIENCE should be on a dietary protein and Phe-restricted diet that is based on blood Phe levels. Patients should undergo regular dietary assessments, including protein and Phe intake, by their healthcare provider [see Dosage and Administration ( 2.2 )].

Increased Bleeding : SEPHIENCE may increase the risk of bleeding. Consider treatment interruption in patients with active bleeding. ( 5.1 ) Hypophenylalaninemia : Some pediatric PKU patients experienced hypophenylalaninemia; monitor patients blood Phe levels during treatment. ( 5.2 ) Interaction with Levodopa : Seizures, over-stimulation or irritability may occur; monitor patients for a change in neurologic status. ( 5.3 ) 5.1 Increased Bleeding SEPHIENCE may increase the risk of bleeding. Bleeding events, including superficial hematomas, prolonged bleeding, and heavy menstrual bleeding have occurred in patients treated with SEPHIENCE [see Adverse Reactions ( 6.1 )] . One patient with non-traumatic superficial hematomas and prolonged bleeding was re-challenged at a lower dose of SEPHIENCE with recurrence of symptoms, which led to treatment discontinuation. The patient experienced symptoms 15 days after initial exposure and two days after rechallenge. The patient had normal blood counts and coagulation studies at the time of the bleeding. Inform the patient about the increased risk of bleeding associated with SEPHIENCE and to follow up with his/her healthcare provider if he/she experiences any signs of increased bleeding. Consider treatment interruption with SEPHIENCE in patients with active bleeding. 5.2 Hypophenylalaninemia In clinical trials of SEPHIENCE, some pediatric PKU patients experienced hypophenylalaninemia (low blood Phe), including some patients with multiple low blood Phe levels, during treatment with SEPHIENCE [see Adverse Reactions ( 6.1 )] .

The following clinically significant adverse reactions are described elsewhere in the labeling: Increased Bleeding [see Warnings and Precautions ( 5.1 )] . Hypophenylalaninemia [see Warnings and Precautions ( 5.2 )] . Most common adverse reactions with SEPHIENCE (≥2% and greater than placebo) were diarrhea, headache, abdominal pain, hypophenylalaninemia, feces discoloration, and oropharyngeal pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact PTC Therapeutics, Inc. at 1-866-562-4620 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of SEPHIENCE was evaluated in Trial 1 [Part 1 (open label); Part 2, (placebo-controlled)]; and Trial 2 (open-label). The two trials included a total of 215 SEPHIENCE-treated patients with PKU: 10 (5%) were <2 years old, 118 (55%) were ≥2 and <17 years old, and 87 (40%) were ≥17 years old. All patients received SEPHIENCE from 7.5 mg/kg/day up to 60 mg/kg/day and the median duration of treatment (in weeks) was 25.5 [see Clinical Studies ( 14.1 )] . Trial 1 Trial 1 included a total of 157 patients (85 male and 72 female, aged 1 year to 61 years old) with PKU across both parts of the trial. The patients received dosages from 20 mg/kg up to 60 mg/kg daily and the median duration of treatment was 8 weeks.

8.1 Pregnancy Risk Summary Available data on the use of SEPHIENCE during pregnancy are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Uncontrolled blood Phe concentrations before and during pregnancy are associated with an increased risk of adverse pregnancy outcomes and fetal adverse effects ( see Clinical Considerations ) . In animal reproduction studies, oral administration of sepiapterin to pregnant rats and rabbits during organogenesis at dose exposures up to 9- and 6- times the human exposure at the maximum recommended human dose (MRHD) of 60 mg/kg, respectively, resulted in no adverse developmental effects ( see Data ). All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage in pregnant women with PKU who maintain blood Phe concentrations greater than 600 micromol/L during pregnancy is greater than the corresponding background risk for pregnant women without PKU.

Metabolism

Following oral administration, sepiapterin reached the maximum concentration in plasma at 2 hours post-treatment and converted to pharmacologically active metabolite BH 4 with the exposures of sepiapterin generally less than 2% of those of BH 4 ( Table 5 ). There was no accumulation for BH 4 following repeated once daily dose up to 60 mg/kg administered in adult healthy volunteers.

• Jul 28, 2025NDANDA219666Ptc Therap

1. 1Drug Ineffective513%
2. 2Product Preparation Error410%
3. 3Abdominal Pain37.7%
4. 4Abdominal Pain Upper37.7%
5. 5Haemorrhage37.7%
6. 6Pregnancy37.7%
7. 7Abortion Spontaneous25.1%
8. 8Amino Acid Level Increased25.1%
9. 9Contusion25.1%
10. 10Diarrhoea25.1%
11. 11Dyspepsia25.1%
12. 12Flatulence25.1%
13. 13Heavy Menstrual Bleeding25.1%
14. 14Product Use Complaint25.1%
15. 15Tooth Discolouration25.1%

The 4 most recently updated of 4 ClinicalTrials.gov registrations naming Sepiapterin as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study of Sepiapterin in Participants With Phenylketonuria (PKU)
  Recruiting · Phase 3 · Interventional · 56 enrolled · PTC Therapeutics
  NCT06302348updated 2026-05-06
• A Long-Term Safety Study of PTC923 in Participants With Phenylketonuria
  Active not recruiting · Phase 3 · Interventional · 200 enrolled · PTC Therapeutics
  NCT05166161updated 2026-04-24
• A Study of PTC923 (CNSA-001) in Primary Tetrahydrobiopterin (BH4) Deficient Participants With Hyperphenylalaninemia
  Completed · Phase 1 · Phase 2 · Interventional · 8 enrolled · PTC Therapeutics
  NCT03519711updated 2023-11-14
• A Study of CNSA-001 in Women With Diabetic Gastroparesis
  Completed · Phase 2 · Interventional · 21 enrolled · PTC Therapeutics
  NCT03712124updated 2022-01-05

Frequently asked questions

How does Sepiapterin work?

SEPHIENCE is a precursor of the enzymatic co-factor tetrahydrobiopterin (BH 4 ) which activates PAH.

What is Sepiapterin used for?

According to FDA labeling, Sepiapterin carries indications including: SEPHIENCE is indicated for the treatment of hyperphenylalaninemia (HPA) in adult and pediatric patients 1 month of age and older with sepiapterin-responsive phenylketonuria (PKU). SEPHIENCE is to be used in conjunction with a phenylalanine (Phe)-restricted diet.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Sepiapterin?

Sepiapterin is classified as Various alimentary tract and metabolism products, Phenylalanine Hydroxylase Activators.

What are the brand names for Sepiapterin?

Sepiapterin is marketed under brand names including Sephience.

What are the contraindications for Sepiapterin?

Sepiapterin labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.