sapropterin
targets PAH via activation
Regulatory milestones approvals, filings & regulatory actions · 4 recorded
| Milestone | Jurisdiction | Brand | Indication | Date | Sentence it was read from |
|---|---|---|---|---|---|
| Label expansions (2) | US (FDA) | KUVAN | — | 2013-12-19 – 2014-04-23 | fda.gov ↗ |
| Approved | EU (EMA) | Kuvan | — | 2008-12-02 | europa.eu ↗ |
| Approved | US (FDA) | KUVAN | — | 2007-12-13 | fda.gov ↗ |
Trials 63 · started per year
| Phase | Registry id | Dates | Indication | Sponsor | Status | Outcome |
|---|---|---|---|---|---|---|
| Phase 02 trials | ||||||
| Phase 0 | NCT02042196 | Dec 2013 → May 2016 | — | University of Colorado, Denver | Completed | No outcome recorded |
| Phase 0 | NCT00208780 | Dec 2004 → Dec 2005 | hypertensive disorder | Emory University | Completed | No outcome recorded |
| Phase 112 trials | ||||||
| Phase 1 | NCT06987773 | Aug 2025 | — | APR Applied Pharma Research s.a. | Completed | No outcome recorded |
| Phase 1 | NCT06481709 | Jul → Aug 2024 | — | APR Applied Pharma Research s.a. | Completed | No outcome recorded |
| Phase 1 | NCT05299203 | May → Dec 2022 | head and neck squamous cell carcinoma | West China Hospital | Unknown | No outcome recorded |
| Phase 1 | NCT05114226 | Mar 2022 → Nov 2023 | radiodermatitis | West China Second University Hospital | Unknown | No outcome recorded |
| Phase 1 | NCT04800692 | Jun 2021 → Jul 2027 expected | intermittent vascular claudication, peripheral arterial disease | Louis Messina | Active not recruiting | No outcome recorded |
| Phase 1 | NCT06312748 | May 2021 → Sep 2028 expected | diastolic heart failure | VA Office of Research and Development | Recruiting | No outcome recorded |
| Phase 1 | NCT04014712 | Apr 2021 → Aug 2022 | chronic obstructive pulmonary disease, tetrahydrobiopterin metabolic process disease | University of Massachusetts, Amherst | Withdrawn | No outcome recorded |
| Phase 1 | NCT03680573 | Jan → May 2018 | cardiovascular disorder | The University of Texas at Arlington | Completed | No outcome recorded |
| Phase 1 | NCT00789568 | Oct 2008 → Jan 2009 | phenylketonuria | BioMarin Pharmaceutical | Completed | No outcome recorded |
| Phase 1 | NCT02966665 | Sep 2008 → Aug 2026 overdue | chronic obstructive pulmonary disease, heart failure, pulmonary arterial hypertension | Russell Richardson | Recruiting | No outcome recorded |
| Phase 1 | NCT00435331 | Mar → Sep 2008 | pulmonary arterial hypertension | Vanderbilt University | Completed | No outcome recorded |
| Phase 1 | NCT00244218 | Apr 2005 → Mar 2009 | phenylketonuria | The University of Texas Medical Branch, Galveston | Terminated | No outcome recorded |
| Phase 1/23 trials | ||||||
| Phase 1/2 | NCT02530996 | Jan → Jun 2016 | rheumatic disorder | VA Office of Research and Development | Completed | No outcome recorded |
| Phase 1/2 | NCT01706965 | Oct 2012 → Jun 2016 | schizoaffective disorder, schizophrenia | New York State Psychiatric Institute | Completed | No outcome recorded |
| Phase 1/2 | NCT01425528 | Aug 2011 → Aug 2013 | GTP cyclohydrolase I deficiency | University of Utah | Completed | No outcome recorded |
| Phase 220 trials | ||||||
| Phase 2 | NCT06396637 | Apr 2024 → Apr 2025 | pancreatic adenocarcinoma | Sun Yat-sen University | Unknown | No outcome recorded |
| Phase 2 | NCT05138887 | Mar 2022 → Oct 2023 | enteritis | West China Second University Hospital | Unknown | No outcome recorded |
| Phase 2 | NCT04054973 | Sep 2019 → Dec 2021 | schizoaffective disorder, schizophrenia | University of Massachusetts, Worcester | Withdrawn | No outcome recorded |
| Phase 2 | NCT02947750 | Oct 2016 → Apr 2027 expected | chronic kidney disease | Emory University | Recruiting | No outcome recorded |
| Phase 2 | NCT02774226 | Sep 2015 → Jul 2018 | chronic obstructive pulmonary disease | Augusta University | Completed | No outcome recorded |
| Phase 2 | NCT01977820 | Feb → Nov 2014 | phenylketonuria | BioMarin Pharmaceutical | Terminated | No outcome recorded |
| Phase 2 | NCT01439555 | Nov 2011 → Nov 2017 | Alzheimer disease | University of Massachusetts, Worcester | Completed | No outcome recorded |
| Phase 2 | NCT01772758 | Aug 2011 → Jun 2016 | cystic fibrosis | Augusta University | Completed | No outcome recorded |
| Phase 2 | NCT01395394 | Jun 2011 → Jun 2013 | phenylketonuria | Emory University | Terminated | No outcome recorded |
| Phase 2 | NCT01356966 | May 2011 → May 2014 | chronic kidney disease | Emory University | Completed | No outcome recorded |
| Phase 2 | NCT00850070 | Mar 2009 → Aug 2011 | autism | The Children's Health Council | Completed | No outcome recorded |
| Phase 2 | NCT00841100 | Dec 2008 → Jul 2011 | phenylketonuria | University of Miami | Completed | No outcome recorded |
| Phase 2 | NCT00802893 | Dec 2008 → May 2009 | cardiovascular disorder | Johns Hopkins University | Terminated | No outcome recorded |
| Phase 2 | NCT00625820 | May → Sep 2008 | chronic kidney disease, proteinuria | University of Michigan | Completed | No outcome recorded |
| Phase 2 | NCT00532844 | Sep 2007 → Nov 2008 | — | BioMarin Pharmaceutical | Completed | No outcome recorded |
| Phase 2 | NCT00445978 | May 2007 → Aug 2008 | sickle cell disease | BioMarin Pharmaceutical | Completed | No outcome recorded |
| Phase 2 | NCT00403494 | Dec 2006 → Nov 2008 | intermittent vascular claudication | BioMarin Pharmaceutical | Completed | No outcome recorded |
| Phase 2 | NCT00355264 | Aug 2006 → Jun 2009 | hyperphenylalaninemia due to tetrahydrobiopterin deficiency | BioMarin Pharmaceutical | Completed | No outcome recorded |
| Phase 2 | NCT00325962 | May → Dec 2006 | hypertensive disorder | BioMarin Pharmaceutical | Completed | No outcome recorded |
| Phase 2 | NCT00104260 | Dec 2004 → Nov 2005 | phenylketonuria | BioMarin Pharmaceutical | Completed | No outcome recorded |
| Phase 2/34 trials | ||||||
| Phase 2/3 | NCT01456286 | Oct 2011 → Oct 2013 | cirrhosis of liver, portal hypertension | Fundacion Clinic per a la Recerca Biomédica | Completed | No outcome recorded |
| Phase 2/3 | NCT00943579 | Aug 2009 → Dec 2011 | autism | The Children's Health Council | Completed | No outcome recorded |
| Phase 2/3 | NCT00935753 | Apr 2009 → Feb 2010 | Lesch-Nyhan syndrome | University of California, San Diego | Withdrawn | No outcome recorded |
| Phase 2/3 | NCT00432822 | — | disorder of phenylalanine metabolism | Orphanetics Pharma Entwicklungs GmbH | Terminated | No outcome recorded |
| Phase 38 trials | ||||||
| Phase 3 | NCT01732471 | Nov 2012 → Oct 2013 | phenylketonuria | Merck KGaA, Darmstadt, Germany | Completed | No outcome recorded |
| Phase 3 | NCT01376908 | Jun 2011 → Jul 2014 | phenylketonuria | BioMarin Pharmaceutical | Completed | No outcome recorded |
| Phase 3 | NCT01114737 | Aug 2010 → Mar 2013 | phenylketonuria | BioMarin Pharmaceutical | Completed | No outcome recorded |
| Phase 3 | NCT00838435 | Feb 2009 → Sep 2018 | phenylketonuria | BioMarin Pharmaceutical | Completed | No outcome recorded |
| Phase 3 | NCT00332189 | Jul 2006 → Aug 2009 | phenylketonuria | BioMarin Pharmaceutical | Completed | No outcome recorded |
| Phase 3 | NCT00272792 | Feb → Nov 2006 | phenylketonuria | BioMarin Pharmaceutical | Completed | No outcome recorded |
| Phase 3 | NCT00225615 | Nov 2005 → Jun 2006 | phenylketonuria | BioMarin Pharmaceutical | Completed | No outcome recorded |
| Phase 3 | NCT00104247 | Mar 2005 → Feb 2006 | phenylketonuria | BioMarin Pharmaceutical | Completed | No outcome recorded |
| Phase 45 trials | ||||||
| Phase 4 | NCT04227080 | Jun 2020 → Dec 2021 | phenylketonuria | Taipei Veterans General Hospital, Taiwan | Unknown | No outcome recorded |
| Phase 4 | NCT03493412 | Jul 2019 | peripheral arterial disease | University of Nebraska | Withdrawn | No outcome recorded |
| Phase 4 | NCT01965912 | Oct 2013 → Jan 2023 | phenylketonuria | BioMarin Pharmaceutical | Completed | No outcome recorded |
| Phase 4 | NCT01617070 | May 2012 → Dec 2014 | phenylketonuria | University of Southern California | Completed | No outcome recorded |
| Phase 4 | NCT01082328 | May 2010 → May 2012 | phenylketonuria | Merck KGaA, Darmstadt, Germany | Completed | No outcome recorded |
| Phase not applicable8 trials | ||||||
| — | NCT02353312 | Mar 2015 → Dec 2018 | heart failure | Providence VA Medical Center | Completed | No outcome recorded |
| — | NCT01806051 | Mar 2013 → May 2014 | phenylketonuria | Dr. Linda Randolph | Terminated | No outcome recorded |
| — | NCT01541397 | Jun 2011 → Aug 2012 | phenylketonuria | The University of Texas Health Science Center, Houston | Terminated | No outcome recorded |
| — | NCT01412437 | Apr 2011 → Mar 2012 | phenylketonuria | Children's National Research Institute | Withdrawn | No outcome recorded |
| — | NCT01398943 | Sep 2010 → Jun 2015 | chronic obstructive pulmonary disease | Augusta University | Completed | No outcome recorded |
| — | NCT01141595 | Jul 2010 → Sep 2011 | autism spectrum disorder | The University of Texas Health Science Center, Houston | Completed | No outcome recorded |
| — | NCT01135186 | May 2010 → Nov 2012 | gastroparesis | Stanford University | Completed | No outcome recorded |
| — | NCT00986973 | Mar 2010 → Jul 2011 | phenylketonuria | Children's Hospital of Philadelphia | Completed | No outcome recorded |
| Phase not stated1 trial | ||||||
| — | NCT00484991 | — | phenylketonuria | BioMarin Pharmaceutical | Approved for marketing | No outcome recorded |
Also used as a comparator or background therapy in 2 trials
| Phase | Registry id | Dates | Indication | Sponsor | Status | Outcome |
|---|---|---|---|---|---|---|
| Phase 11 trial | ||||||
| Phase 1 | NCT07255599 Comparator | Sep 2025 → Jan 2026 overdue | phenylketonuria | Sohag University | Active not recruiting | No outcome recorded |
| Phase 21 trial | ||||||
| Phase 2 | NCT00423280 Comparator | Nov 2006 → Feb 2009 | coronary artery disorder | University of Oxford | Unknown | No outcome recorded |
Press releases naming this drug 1 release
| Date | Issuer | Release |
|---|---|---|
| 2013-11-29 | Daiichi Sankyo | Daiichi Sankyo Launches Natural Tetrahydrobiopterin Agent Biopten® Granules 10% daiichisankyo.com ↗ |
Evidence & citations 15 cited values
Every value below carries the sentence it was read from. 73 sources stand behind the page.
| Field | Value | Cited text |
|---|---|---|
| Known as | Sapropterin | “The primary objective of the study is to evaluate the proportion of responders (that is, greater than or equal to \[\>=\] 30 percent reduction from Baseline in blood...” NCT01082328 ↗24“The aim of the SPARK (Safety Paediatric efficAcy phaRmacokinetic with Kuvan®) trial was to assess the efficacy (improvement in daily phenylalanine tolerance, neuromotor...” PMID 28274234 ↗ Mar 2017 “Sapropterin dihydrochloride (subsequently referred to as sapropterin) (Kuvan®) was approved by the FDA for the treatment of hyperphenylalaninemia in 2007.” NCT00789568 ↗ “Kuvan® (sapropterin dihydrochloride) will be administered orally at a dose of 20 milligram per kilogram per day (mg/kg/day) once daily for 8 days.” NCT01732471 ↗ “Tetrahydrobiopterin (BH4), also known as Sapropterin, is an important cofactor of the nitric oxide synthase (NOS) enzyme.” NCT05114226 ↗ “Tetrahydrobiopterin (BH4), also known as Sapropterin, is an important cofactor of the nitric oxide synthase (NOS) enzyme.” NCT05138887 ↗ |
| Known as | (6R)-5,6,7,8-Tetrahydrobiopterin dihydrochloride | “This site will receive 10 mM (6R)-5,6,7,8-Tetrahydrobiopterin dihydrochloride (BH4) at an infusion rate of 2 µl/min.” NCT03680573 ↗ |
| Known as | 5,6,7,8-Tetrahydrobiopterin | “5,6,7,8-Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide synthases (NOS) and aromatic amino acid hydroxylases, and its biosynthesis involves de novo...” PMID 34513700 ↗ Aug 20211“5,6,7,8-Tetrahydrobiopterin (BH4) is an essential cofactor for all nitric oxide synthases.” PMID 28596000 ↗ Jun 2017 |
| Known as | 6R-BH4 | “Efficacy of sapropterin dihydrochloride (tetrahydrobiopterin, 6R-BH4) for reduction of phenylalanine concentration in patients with phenylketonuria: a phase III randomised...” PMID 17693179 ↗ Aug 20076“The purpose of this study is to determine whether the addition of sapropterin dihydrochloride (6R-BH4) to existing treatment has any effect in patients with pulmonary arterial...” NCT00435331 ↗ |
| Known as | 6R-tetrahydrobiopterin | “6R-tetrahydrobiopterin (6R-BH4 or sapropterin dihydrochloride) is an investigational oral drug” NCT00625820 ↗ |
| Known as | BH4 | “Tetrahydrobiopterin（BH4）, also known as sapropterin, has been shown not only to reduce the severity of acute radiation dermatitis but also to enhance the repair of skin injury...” NCT05299203 ↗17“The purpose of this study is to assess the efficacy of supplementation with tetrahydrobiopterin (BH4) for improving vascular and muscle function in patients with COPD and...” NCT04014712 ↗ “The FDA recently approved a new medication, Kuvan, a synthetic form of tetrahydrobiopterin (BH4) manufactured by BioMarin Pharmaceutical Inc., for patients with PKU.” NCT01617070 ↗ “Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide (NO) synthesis and a regulator of endothelial function.” PMID 29705218 ↗ Apr 2018 “Tetrahydrobiopterin (BH4), also known as Sapropterin, is an important cofactor of the nitric oxide synthase (NOS) enzyme.” NCT05114226 ↗ “Tetrahydrobiopterin (BH4), also known as Sapropterin, is an important cofactor of the nitric oxide synthase (NOS) enzyme.” NCT05138887 ↗ “Tetrahydrobiopterin (BH(4)) is a cofactor for the nitric oxide (NO) synthase enzymes” PMID 18322548 ↗ Mar 2008 “Tetrahydrobiopterin (BH4) is a cofactor for the nitric oxide (NO) synthase enzymes” NCT00208780 ↗ “Tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide synthase” PMID 26962106 ↗ Mar 2016 “Sapropterin Dihydrochloride (BH4, tetrahydrobiopterin)” NCT07255599 ↗ “Sapropterin Dihydrochloride (BH4, tetrahydrobiopterin)” NCT03493412 ↗ “tetrahydrobiopterin (BH4)” NCT00432822 ↗ “BH4” NCT00244218 ↗ |
| Known as | Kuvan | “During the initial 26-week SPARK (Safety Paediatric efficAcy phaRmacokinetic with Kuvan®) study, addition of sapropterin dihydrochloride (Kuvan®; a synthetic formulation of the...” PMID 34344399 ↗ Aug 202113“A Pilot, Phase 1, Randomized, Open-Label, Single-Dose, Four-Way Crossover Study to Compare the Pharmacokinetics of Sapropterin Dihydrochloride 100 mg/mL Oral Suspension...” NCT06481709 ↗ “The primary objective of the study is to evaluate the proportion of responders (that is, greater than or equal to \[\>=\] 30 percent reduction from Baseline in blood...” NCT01082328 ↗ “Kuvan® (sapropterin dihydrochloride) will be administered orally at a dose of 20 milligram per kilogram per day (mg/kg/day) once daily for 8 days.” NCT01732471 ↗ “oral administration of 20 mg/kg KUVAN (BH4)” NCT04227080 ↗ |
| Known as | Phenoptin | “The primary objective is to evaluate the degree and frequency of response to Phenoptin™ (sapropterin dihydrochloride), as demonstrated by a reduction in blood phenylalanine...” NCT00104260 ↗ |
| Known as | RLF-OD032 | “A Pilot, Phase 1, Randomized, Open-Label, Single-Dose, Four-Way Crossover Study to Compare the Pharmacokinetics of Sapropterin Dihydrochloride 100 mg/mL Oral Suspension...” NCT06481709 ↗1“A) A single 10 mg/kg dose of a 100 mg/mL oral suspension of sapropterin dihydrochloride (RLF-OD032) , administered under fed conditions without water followed by B) A single 10...” NCT06987773 ↗ |
| Known as | sapropterin dihydrochloride | “The primary objective is to evaluate the degree and frequency of response to Phenoptin™ (sapropterin dihydrochloride), as demonstrated by a reduction in blood phenylalanine...” NCT00104260 ↗21“In each period, subjects will receive a single 10 mg/kg dose of sapropterin dihydrochloride on Day 1, under fasting or fed conditions, and with or without water, followed by 24...” NCT06481709 ↗ “Efficacy of sapropterin dihydrochloride (tetrahydrobiopterin, 6R-BH4) for reduction of phenylalanine concentration in patients with phenylketonuria: a phase III randomised...” PMID 17693179 ↗ Aug 2007 “The sapropterin EAP (SEAP) is an open-label, multi-center program designed to provide access to sapropterin dihydrochloride for patients diagnosed with hyperphenylalaninemia due to PKU.” NCT00484991 ↗ “Sapropterin dihydrochloride (sapropterin, Kuvan®) is the only US- and EU-approved pharmaceutical version of naturally occurring 6R-BH(4), the cofactor required for PAH activity.” PMID 21646032 ↗ Mar 2011 “In each period, subjects will receive a single 10 mg/kg dose of sapropterin dihydrochloride on Day 1, under fed conditions, followed by 24 hours of PK sampling.” NCT06987773 ↗ “Kuvan® or sapropterin dihydrochloride is a synthetic preparation of the dihydrochloride salt of naturally occurring tetrahydrobiopterin (BH4).” NCT01772758 ↗ “A Phase 2 Study of the Effects of Sapropterin Dihydrochloride on Symptomatic Peripheral Arterial Disease” NCT00403494 ↗ “6R-tetrahydrobiopterin (6R-BH4 or sapropterin dihydrochloride) is an investigational oral drug” NCT00625820 ↗ “Sapropterin Dihydrochloride (BH4, tetrahydrobiopterin)” NCT07255599 ↗ “Sapropterin Dihydrochloride (BH4, tetrahydrobiopterin)” NCT03493412 ↗ “6R-BH4 (sapropterin dihydrochloride)” NCT00325962 ↗ “Drug: sapropterin dihydrochloride” NCT01141595 ↗ |
| Known as | tetrahydrobiopterin | “Tetrahydrobiopterin（BH4）, also known as sapropterin, has been shown not only to reduce the severity of acute radiation dermatitis but also to enhance the repair of skin injury...” NCT05299203 ↗14“Efficacy of sapropterin dihydrochloride (tetrahydrobiopterin, 6R-BH4) for reduction of phenylalanine concentration in patients with phenylketonuria: a phase III randomised...” PMID 17693179 ↗ Aug 2007 “therapeutic efficacy of the pharmacologic compound tetrahydrobiopterin (BH4) in SSc” NCT02530996 ↗ “Sapropterin Dihydrochloride (BH4, tetrahydrobiopterin)” NCT03493412 ↗ “Sapropterin Dihydrochloride (BH4, tetrahydrobiopterin)” NCT07255599 ↗ |
| Known as | Tetrahydrobiopterin (BH4) | ClinicalTrials.gov intervention name — accepted as the source's own label NCT02774226 ↗ |
| Action | Activate | “Sapropterin enhances residual PAH activity in sapropterin-responsive PKU patients” PMID 21646032 ↗ Mar 2011 |
| Route | Oral | “We randomly assigned 42 patients to receive oral doses of sapropterin (10 mg/kg) and 47 patients to receive placebo, once daily for 6 weeks.” PMID 17693179 ↗ Aug 2007 |
| Target | PAH | “Sapropterin enhances residual PAH activity in sapropterin-responsive PKU patients” PMID 21646032 ↗ Mar 2011 |