Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
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 PTC923, Sephience, CNSA-001
Sepiapterin · 5 trials · 4 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.
Participants consumed 150 milliliters (mL) of Ensure™ every 5 minutes for the nutrient satiety test. At 5-minute intervals, participants scored their fullness using a rating scale that combines verbal descriptors on a scale graded 0 to 5 (0 = no symptoms, 1 = first sensation of fullness \[threshold\], 2 = mild, 3 = moderate, 4 = severe and 5 = maximum or unbearable fullness). Participants were told to stop when a score of 5 was obtained. The actual volume of Ensure™ consumed at this point was the maximum tolerated volume.
Participants consumed 150 mL of Ensure™ every 5 minutes for the nutrient satiety test. At 5-minute intervals, participants scored their fullness using a rating scale that combines verbal descriptors on a scale graded 0 to 5 (0: no symptoms, 1 = first sensation of fullness \[threshold\], 2 = mild, 3 = moderate, 4 = severe and 5 = maximum or unbearable fullness). Participants were told to stop when a score of 5 was obtained. The actual volume of Ensure™ consumed at this point was the maximum tolerated volume.
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. |
| CNSA-001 | EXPERIMENTAL | Participants will receive CNSA-001 20 mg/kg/day (10 mg/kg twice daily \[BID\]) as an oral suspension for 14 days. |
| Placebo | PLACEBO_COMPARATOR | Participants will receive placebo matching to CNSA-001 BID for 14 days. |
| 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 |
| CNSA-001 | DRUG | CNSA-001 Powder for Suspension |
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 |
Sepiapterin is an investigational small molecule being developed for the treatment of phenylketonuria (PKU), a metabolic disorder. It is currently in Phase 3 clinical development and has not been approved by regulatory authorities.
Sepiapterin targets the enzyme phenylalanine hydroxylase (PAH). By targeting PAH, the drug aims to address the underlying enzyme deficiency in phenylketonuria, potentially helping to manage phenylalanine levels in patients.
Sepiapterin is being developed by PTC Therapeutics, Inc., a biopharmaceutical company. PTC Therapeutics is publicly traded under the ticker symbol PTCT on the NASDAQ stock exchange.
Sepiapterin is currently in Phase 3 clinical development. It is an investigational drug, meaning it has not yet been approved by the FDA or other regulatory agencies for the treatment of phenylketonuria.
Sepiapterin is being studied in a Phase 3 clinical trial with the identifier NCT06302348. This trial is recruiting participants with phenylketonuria and is being conducted in the United States, Australia, France, Ireland, Poland, and the United Kingdom.