FDA

Sephience

Approved 28 Jul 2025OralPowder

The FDA lists this product in 2 strengths and forms.

Indications

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. SEPHIENCE is a phenylalanine hydroxylase (PAH) activator 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. ( 1 )

Contraindications

None. None. ( 4 )

Warnings and precautions

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 )

5.1Increased 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.

5.2Hypophenylalaninemia

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 )] . Prolonged levels of blood Phe that are too low have been associated with catabolism and endogenous protein breakdown, which has been associated with adverse developmental outcomes. Monitor blood Phe levels during treatment and if needed, modify the dosage of SEPHIENCE and/or dietary protein and Phe intake to ensure adequate blood Phe level control.

At a glance

Brand name: Sephience
Active substance: sepiapterin
Route: Oral
Dosage form: Powder
Applicant: PTC Therap
Status: Prescription
FDA approval: 28 Jul 2025
Application: NDA219666-001

Indications

SEPHIENCE is to be used in conjunction with a phenylalanine (Phe)- restricted diet. ( 1 )

Warnings and precautions

5.1Increased Bleeding

5.2Hypophenylalaninemia

Pregnancy and breastfeeding

8.1Pregnancy 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.

Clinical Considerations Disease-Associated Maternal and/or Embryofetal Risk Uncontrolled blood Phe concentrations before and during pregnancy are associated with an increased risk of adverse outcomes and fetal adverse effects ( see Data ). To reduce the risk of hyperphenylalaninemia-induced fetal adverse effects, blood Phe concentrations should be maintained between 120 and 360 micromol/L during pregnancy and during the 3 months before conception [see Dosage and Administration ( 2.2 )] .

Data Human Data Available data from the Maternal Phenylketonuria Collaborative Study on 468 pregnancies and 331 live births in pregnant women with PKU demonstrated that uncontrolled Phe concentrations above 600 micromol/L are associated with an increased risk for major birth defects (including microcephaly, major cardiac malformations), intrauterine fetal growth retardation, and future intellectual disability with low IQ.

Animal Data In an embryo-fetal development study in rats, SEPHIENCE was administered at dose levels of 100, 300, or 1,000 mg/kg/day via oral gavage to pregnant rats during the period of organogenesis from gestation day (GD) 7 to GD 17. There were no maternal or embryo-fetal developmental toxicities noted at doses up to 1,000 mg/kg/day (9-fold the human AUC 0-24 at the MRHD). In an embryo-fetal development study in pregnant rabbits, SEPHIENCE was administered at dose levels of 100, 300, or 1,000 mg/kg/day via oral gavage to pregnant rabbits during the period of organogenesis from gestation day (GD) 7 to GD 19.

There were no maternal or embryo-fetal developmental toxicities at doses up to 1,000 mg/kg/day (6-fold the human AUC 0-24 at the MRHD). In the pre- and post-natal development study in rats, SEPHIENCE was administered at dose levels of 30, 100, and 300 mg/kg/day via oral gavage once daily to pregnant rats from GD 6 to lactation day 20. SEPHIENCE did not induce effects on maternal reproductive function or on developmental and reproductive parameters of male and female offspring up to 300 mg/kg (7-fold the human AUC 0-24 at the MRHD).

Adverse reactions

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.

6.1Clinical 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. Table 4 lists the most common adverse reactions that were reported in ≥2% of patients treated with SEPHIENCE and greater than that of the placebo group in Part 2 of Trial 1.

Table 4: Adverse Reactions for SEPHIENCE in Adult and Pediatric Patients with PKU that Occurred in ≥2% of Sepiapterin-Treated Patients and Greater than Placebo (Trial 1 Part 2) a Includes Abdominal pain; Abdominal pain upper, Abdominal discomfort. Adverse Reaction SEPHIENCE N=56 N (%) Placebo N=54 N (%) Diarrhea 4 (7) 1 (2) Headache 4 (7) 1 (2) Abdominal pain a 3 (5) 1 (2) Hypophenylalaninemia 2 (4) 0 Feces discoloration 2 (4) 0 Oropharyngeal pain 2 (4) 1 (2) Adverse reactions were similar across both adult and pediatric populations except for hypophenylalaninemia ( see Description of Selected Adverse Reactions ).

Description of Selected Adverse Reactions Increased Bleeding In Trial 1 Part 2, a case of heavy menstrual bleeding was reported in a SEPHIENCE-treated patient. Less than 2% of patients in Trial 2 experienced increased bleeding, which included heavy menstrual bleeding, non-traumatic superficial hematomas, and prolonged bleeding. Hypophenylalaninemia In Trial 1 Part 2, hypophenylalaninemia was seen in 5% (2/37) of sepiapterin-treated pediatric patients and in no adult patients.

Some pediatric patients in Trial 2 had multiple low blood Phe levels.

Sephience

Indications

Contraindications

Warnings and precautions

5.1Increased Bleeding

5.2Hypophenylalaninemia

At a glance

Two medicines in one question?

Sephience

Indications

Contraindications

Warnings and precautions

5.1Increased Bleeding

5.2Hypophenylalaninemia

At a glance

Two medicines in one question?

Interactions

7.1Effects of Other Drugs on

7.2Effects of

7.3Drugs Affecting Nitric Oxide-Mediated Vasorelaxation

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

Composition

Strengths and forms

Official product information