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Label indication 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. FDA label
Also known as Sepiapterin, Sephience
PTC923 · 4 trials · 3 indications
Analysis for participants ≥30 months to \<6 years of age.
Analysis for participants ≥6 years to 16 years of age.
A TEAE is any unfavorable or unintended sign (including an abnormal laboratory finding), symptom or disease in a study participant who is administered study drug in this study
Phe tolerance is defined as the total amount of dietary Phe (milligrams \[mg\]/kilogram \[kg\] per day) ingested while maintaining blood Phe levels within the range of 40 to 360 micromoles (μmol)/liter (L) (defined as ≥40 to \<360 μmol/L).
Baseline was defined as the average of Day -1 and Day 1 predose blood Phe levels in Part 2, and mean level at Weeks 5 and 6 was calculated as the average of blood Phe levels collected during the Week 5-6 analysis visit window. Least square (LS) mean and standard error (SE) were calculated using mixed model repeated measures (MMRM) method.
Baseline was defined as the average of Day -1 and Day 1 predose blood Phe levels in Part 2, and mean level at Weeks 5 and 6 was calculated as the average of blood Phe levels collected during the Week 5-6 analysis visit window. LS mean and SE were calculated using MMRM method.
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs. TEAEs were defined as AEs that commenced or worsened after the first dose of study drug. A summary of other non-serious AEs and all SAEs, regardless of causality is located in the 'Reported AE section'.
| Arm | Type | Description |
|---|---|---|
| Sepiapterin | EXPERIMENTAL | Participants will receive age- and weight-adjusted doses of sepiapterin orally once daily for up to 6 years. |
| PTC923 | EXPERIMENTAL | Participants will receive PTC923 7.5 mg/kg (participants 0 to \<6 months of age), 15 mg/kg (participants 6 to \<12 months of age), 30 mg/kg (participants 12 months to \<2 years of age), or 60 mg/kg (participants ≥2 years of age) orally once daily for a minimum of 12 months or until participant experiences lack of efficacy, adverse events (AEs) that lead to discontinuation, withdraws from treatment, or PTC923 is authorized and commercially available in the specific country. |
| Part 1: PTC923 | EXPERIMENTAL | Participants will receive PTC923 7.5 milligrams (mg)/kilogram (kg) (participants 0 to \<6 months of age), 15 mg/kg (participants 6 to \<12 months of age), 30 mg/kg (participants 12 months to \<2 years of age), or 60 mg/kg (participants ≥2 years of age) orally once daily for 14 days. |
| Part 2: PTC923 | EXPERIMENTAL | Participants will receive PTC923 20 mg/kg daily for Weeks 1 and 2, then PTC923 40 mg/kg daily for Weeks 3 and 4, then PTC923 60 mg/kg daily for Weeks 5 and 6. |
| Part 2: Placebo | PLACEBO_COMPARATOR | Participants will receive equivalent quantities of placebo to match the 20 to 40 to 60 mg/kg dose escalation of the PTC923 treatment arm. |
| Cohort 1: PTC923 2.5 and 10 mg/kg/day | EXPERIMENTAL | Participants will receive PTC923 suspension 2.5 milligrams (mg)/kilogram (kg)/day (dose divided in 2 for twice daily administration) orally for 7 days in Period 1, undergo a 3 (±1) day washout period, then escalate to a dose of 10 mg/kg/day (dose divided in 2 for twice daily administration) administered orally for 7 days in Period 2 (14 days total treatment). |
| Cohort 2: PTC923 5 and 20 mg/kg/day | EXPERIMENTAL | Participants will receive PTC923 suspension 5 mg/kg/day (dose divided in 2 for twice daily administration) orally for 7 days in Period 1, undergo a 3 (±1) day washout period, then escalate to a dose of 20 mg/kg/day (dose divided in 2 for twice daily administration) administered orally for 7 days in Period 2 (14 days total treatment). |
| Name | Type | Description |
|---|---|---|
| Sepiapterin | DRUG | Sepiapterin powder for oral use will be mixed in water or apple juice prior to administration. |
| PTC923 | DRUG | PTC923 powder for oral use will be suspended in water or apple juice prior to administration. |
| Placebo | DRUG | Placebo matching to PTC923 |
Key Inclusion Criteria: For all participants: * Women of childbearing potential must have a negative pregnancy test at Screening and agree to abstinence or the use of at least one highly effective form of contraception for the duration of the study, and for at least 90 days after the last dose of ...
Top 5 of 7 competitors
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| BioMarin Pharmaceutical Inc. | BMRN | 5 | PHASE3 | Pegvaliase, BMN 307 |
| PTC Therapeutics, Inc. | PTCT | 1 | PHASE3 | Sepiapterin |
| Maze Therapeutics, Inc. | MAZE | 1 | PHASE2 | MZE782 |
| Sanofi SA Sponsored ADR | SNY | 1 | PHASE1 | SAR444836 |
| Agios Pharmaceuticals, Inc. | AGIO | 1 | PHASE1 | AG-181 |
PTC923 is an investigational oral small molecule developed by PTC Therapeutics for rare metabolic disorders involving elevated phenylalanine. It is being studied in phenylketonuria (PKU) and in primary tetrahydrobiopterin (BH4) deficiency with hyperphenylalaninemia. It is a synthetic formulation of sepiapterin, a natural precursor of BH4.
PTC923 is being developed to lower blood phenylalanine levels in patients with phenylketonuria, a rare inherited disorder of phenylalanine metabolism. Clinical studies have enrolled participants with PKU, including a long-term safety study and a separate Phase 3 study, both of which have been completed.
PTC923 targets sepiapterin reductase, an enzyme in the tetrahydrobiopterin (BH4) biosynthetic pathway. By supplying sepiapterin, the drug is intended to increase intracellular BH4, a cofactor required for the enzyme phenylalanine hydroxylase to convert phenylalanine to tyrosine, thereby reducing phenylalanine accumulation.
PTC923 is being developed by PTC Therapeutics, Inc., a biopharmaceutical company that trades on the Nasdaq under the ticker symbol PTCT. The company is advancing the asset for rare metabolic diseases, including phenylketonuria and BH4 deficiency.
PTC923 is an investigational drug and has not been approved by the FDA. Its clinical program includes completed Phase 3 trials in phenylketonuria and a completed Phase 1 study in primary BH4 deficiency with hyperphenylalaninemia. The overall program stage is listed as Phase 1, with no trials currently active.
PTC923 has been studied in completed trials including NCT05166161, a long-term safety study in phenylketonuria with 247 participants, and NCT05099640, a Phase 3 study in phenylketonuria with 157 participants. NCT03519711 was a Phase 1 study in primary BH4 deficiency with hyperphenylalaninemia enrolling 8 participants.
Yes, PTC923 has also been referred to as CNSA-001. The Phase 1 study in primary BH4 deficiency with hyperphenylalaninemia was registered under the name PTC923 (CNSA-001), confirming that the two names refer to the same investigational compound.