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Label indication KUVAN ® is indicated to reduce blood phenylalanine (Phe) levels in adult and pediatric patients one month of age and older with hyperphenylalaninemia (HPA) due to tetrahydrobiopterin- (BH4-) responsive Phenylketonuria (PKU). KUVAN is to be used in conjunction with a Phe-restricted diet. FDA label
Also known as sapropterin dihydrochloride, sapropterin dihydrochloride (6R-BH4), Kuvan, Phenoptin, BH4, 6R BH4
sapropterin · 15 trials · 9 indications
Phe tolerance was defined as the amount of dietary Phe prescribed (milligram per kilogram per day \[mg/kg/day\]) while maintaining blood Phe levels within the selected therapeutic target range (defined as greater than or equal to \[\>=\] 120 to less than \[\<\] 360 micromoles per liter \[mcmol/L\]).
Effects of 6R-BH4 on symptoms of ADHD in PKU subjects who had symptoms of ADHD at screening in the subjects that had a blood Phe level reduction after treatment with 6R-BH4. The total ADHD-RS score and the corrected total ARS score range from 0 to 54, with higher scores corresponding to worse severity of ADHD symptoms.
Effects of 6R-BH4 on global function in PKU subjects in subjects that had a blood Phe level reduction after treatment with 6R-BH4 at screening. The CGI-I is a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the intervention and rated as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse.
Full Scale Intelligence Quotient (FSIQ) is a score derived through administration of selected subtests from age appropriate Wechsler Intelligence assessments. Weschler Preschool and Primary Scale of Intelligence (WPPSI)-III is used for children \>30 months and ≤6 years; and Weschler Intelligence Scale for Children (WISC)-IV is used for children \>6 years old. The outcome variable will be the FSIQ score from WPPSI-III and/or WISC-IV tests. FSIQ results can range from 40 being the lowest and 160 being the highest. Higher scores are associated with higher intelligence quotient.
Safety was assessed with regards to the rate and type of AEs, clinically significant changes to vital signs and/or physical examination findings, and clinically significant changes in laboratory test results.
Plasma BH4 concentration area under the curve (AUC0-12 hrs) at the end of each regimen in subjects with endothelial dysfunction.
A treatment-emergent adverse events (TEAE) is any adverse events that newly appeared, increased in frequency or worsened in severity following initiation of study drug administration.
This is to assess the effect of oral sapropterin dihydrochloride versus placebo on peak walking time (PWT) in subjects with intermittent claudication (IC) caused by peripheral arterial disease (PAD).
Adverse events were described and summarized with focus on treatment- emergent events (TEAEs). A TEAE was defined as any AE that presented , increased in frequency or worsened in severity following initiation of study drug administration. If the onset of an AE was missing then the AE was considered treatment emergent. Drug-related AEs are AEs classified by the investigator as possibly or probably related to study drug.
Baseline blood phenylalanine(Phe) value is the latest measurement taken prior to initiation of Phenoptin treatment. The ideal range for blood Phe levels is approximately 120-360 µmol/L.
Baseline blood phenylalanine(Phe) value is the latest measurement taken prior to initiation of Phenoptin treatment. The objective of this outcome was to compare to Phe levels achieved using previous treatment regimens.
Identify dosing range of oral Kuvan® necessary and sufficient to normalize CSF BH4 levels in adults with GTPCH Deficiency.
| Arm | Type | Description |
|---|---|---|
| Kuvan® + Phe-restricted diet | EXPERIMENTAL | Subjects will be treated with Kuvan® tablets once daily along with Phe-restricted diet therapy. |
| Phe-restricted diet alone | OTHER | Subjects will follow a Phe-restricted diet alone. |
| Sapropterin dihydrochloride | EXPERIMENTAL | - |
| Tablet without active ingredient | PLACEBO_COMPARATOR | - |
| Placebo | PLACEBO_COMPARATOR | Placebo, provided as tablets similar to Phenoptin tablets, was administered orally once daily in the morning as the number of tablets equivalent to a 20mg/kg/day dose dissolved in 4 8 oz (120-240 mL) of water or apple juice. for 6 weeks. A follow-up call or visit was made 4 weeks later during this double-blind, placebo-controlled study. |
| Sapropterin dihydrochloride+Vitamin C | EXPERIMENTAL | Sapropterin dihydrochloride 5 mg/kg and 500 mg Vitamin C twice a day administered as whole tablets orally within 1 hour after morning and evening meals for 13 days and the last dose within 1 hour after a morning meal on Day 14 and Day 28. |
| Single Arm on Active Drug | EXPERIMENTAL | 5mg/kg/day orally, dose may be adjusted to between 5-20 mg/kg/day by investigator at week 6 to control blood Phe levels Outcomes were also evaluated by the subject's type of BH4 deficiency either defects in the genes encoding the enzymes involved in biosynthesis or defects in the genes encoding the enzymes involved in recycling. |
| 1 | EXPERIMENTAL | Open Label |
| Kuvan Cohort 1 | EXPERIMENTAL | This cohort will be enrolled first. Analysis will be done to determine the optimum dosing of Kuvan to normalize BH4 levels in the Cerebral Spinal Fluid. This cohort will begin at a dose of 20mg/kg/day. |
| Kuvan Cohort 2 | EXPERIMENTAL | Participants in cohort 2 will be enrolled after the analysis of cohort 1 data has taken place. Dosing for cohort 2 will be based on results obtained in cohort 1, but will plan on starting at 30 mg/kg/day. |
| Sapropterin Dihydrochloride 100mg/kg and placebo Moxifloxacin | EXPERIMENTAL | A single dose of 100mg/kg of Sapropterin Dihydrochloride taken along with placebo Moxifloxacin. |
| Sapropterin Dihydrochloride 20mg/kg and placebo Moxifloxacin | EXPERIMENTAL | A single dose of 20mg/kg of Sapropterin Dihydrochloride taken along with a placebo Moxifloxacin. |
| Sapropterin Dihydrochloride placebo and Moxifloxacin | ACTIVE_COMPARATOR | No placebo tablets for Sapropterin Dihydrochloride will be administered, but instead will be apple juice only, taken along with 400mg of Moxifloxacin. |
| Sapropterin Dihydrocholide placebo and Moxifloxacin placebo | PLACEBO_COMPARATOR | No placebo tablets for Sapropterin Dihydrochloride will be administered, but instead will be apple juice only, taken along with placebo of Moxifloxacin. |
| Name | Type | Description |
|---|---|---|
| Kuvan® | DRUG | Kuvan® (sapropterin dihydrochloride) tablets will be administered orally at the dose of 10 mg/kg/day and will be escalated to 20 mg/kg/day if after 4 weeks a subject's Phe tolerance is not increased by at least 20% versus baseline. |
| Phenylalanine (Phe)-restricted diet | OTHER | Phe intake will be adjusted every 2 weeks, based on the mean Phe levels of the previous 2 weeks using pre-defined Phe adjustment criteria. |
| Sapropterin dihydrochloride | DRUG | A dose of 20 mg/kg/day will be administered. Route of administration is oral (intact). |
| Placebo | DRUG | Placebo (tablet without active ingredient) is dosed once/day for the first 13 weeks of the study. |
| sapropterin dihydrochloride, 6R-BH4, tetrahydrobiopterin | DRUG | - |
| Sapropterin Dihydrochloride and Vitamin C | DRUG | Sapropterin Dihydrochloride 5 mg/kg and 500 mg Vitamin C twice a day administered as whole tablets orally within 1 hour after morning and evening meals for 13 days and the last dose within 1 hour after a morning meal on Day 14 and Day 28. |
| Phenoptin | DRUG | 5mg/kg/day orally, dose may be adjusted to between 5-20 mg/kg/day by investigator at week 6 to control blood Phe levels |
| sapropterin dihydrochloride (6R-BH4) | DRUG | 2.5 mg/kg/day for two weeks, 5 mg/kg/day for two weeks, 10 mg/kg/day for four weeks, then 20 mg/kg/day for two days |
| Sapropterin | DRUG | Sapropterin will be taken daily for 12 or 24 weeks. Starting dose will be 20mg/kg/day and will increase at the 8 week visit to 30 mg/kg/day. Dosing may be further increased to as high as 40 mg/kg/day in attempt to normalize BH4 levels in CSF. Starting dose for Cohort 2 will be determined from data analysis in Cohort 1. |
| Moxifloxacin | DRUG | Moxifloxacin is included as a positive control to demonstrate the assay sensitivity based on the expected increased QTc response. |
| Moxifloxacin placebo | DRUG | Moxifloxacin placebo tablet |
Inclusion Criteria: * Male or female PKU infants and young children less than (\<) 4 years of age at the scheduled Day 1 visit of the 26-week study period (taking into consideration the maximum of 21 days in the screening period) * Confirmed clinical and biochemical PKU, including at least two prev...
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 |
Sapropterin is a small molecule studied in phenylketonuria (PKU), GTP cyclohydrolase deficiency, endothelial dysfunction, intermittent claudication, pulmonary arterial hypertension, and sickle cell disease. It has been evaluated in eight completed clinical trials enrolling about 1,402 participants, including Phase 3 studies in PKU and a Phase 1 study in GTP cyclohydrolase deficiency.
Sapropterin targets phenylalanine hydroxylase (PAH) as an activator. By activating PAH, it supports the conversion of phenylalanine to tyrosine, which is relevant in conditions such as phenylketonuria where this enzyme activity is impaired.
Sapropterin is developed by BioMarin Pharmaceutical Inc., which trades under the ticker BMRN. BioMarin is the company associated with the sapropterin clinical program across its studied indications.
Sapropterin is in Phase 2 development overall. Its clinical program includes completed Phase 1, Phase 2, and Phase 3 trials, but no active trials are currently listed. It is an investigational small molecule and is not described as approved in the available data.
Sapropterin has been studied in eight completed trials, including NCT01425528 in GTP cyclohydrolase deficiency, NCT01114737 and NCT00838435 in phenylketonuria, and NCT00789568 evaluating QTc intervals in healthy adults. All listed trials are completed, with no active trials reported.
Yes, sapropterin is also known as sapropterin dihydrochloride, 6R-BH4, and tetrahydrobiopterin. These names refer to the same small molecule developed by BioMarin Pharmaceutical Inc. under the ticker BMRN.