PAH phenylalanine hydroxylase
ENSG00000171759 · protein coding · Open Targets profile
Catalyzes the hydroxylation of L-phenylalanine to L-tyrosine. .
Each band is a group of drugs. It runs from the kind of drug on the left to the furthest stage that drug has reached in any disease on the right. Thicker bands mean more drugs.
Approved bands are highlighted. Withdrawn means the drug was pulled from the market or from development. A combined phase counts as the later one (Phase 1/2 is shown as Phase 2). Hover a band for the drug names. Source: Open Targets Platform, fetched live.
Each row is a cancer, strongest overall evidence first. The two dots show how strong the inherited (germline) and tumour-mutation (somatic) evidence is; the line between them is the gap.
Scores run from 0 (no evidence) to 1 (strongest). A missing dot at 0 means Open Targets holds no evidence of that kind. Source: Open Targets Platform, fetched live.
Tractability
- Small molecule
- Approved Drug, Structure with Ligand, High-Quality Pocket, Druggable Family
- PROTAC
- Half-life Data, Small Molecule Binder
gnomAD loss of function constraint: o/e 1.031499981880188 (upper bound 1.2700999975204468). Low values mean loss of function is poorly tolerated, a safety flag for inhibition.
Who runs trials of these drugs
Principal investigators and study chairs on 16 registry trials, updated in the last three years, of the most advanced drugs against PAH (sapropterin), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Joe NoceraEmory University · 1 of 1 trials Phase 2+
- Kathryn J SwobodaUniversity of Utah · 1 of 1 trials Phase 2+
- Neil SmithCensa Pharmaceuticals · 1 of 1 trials Phase 2+
- David W. WrayVA Salt Lake City Health Care System, Salt Lake City, UT · 0 of 2 trials Phase 2+
- David W WrayUniversity of Utah · 0 of 1 trials Phase 2+
- Louis M MessinaUMASS Medical School · 0 of 1 trials Phase 2+
- Mark L. FreedmanCanada, Ontario - Pharma Medica Research Inc. 4770 Sheppard Ave E · 0 of 1 trials Phase 2+
- Paul LeesonUniversity of Oxford, John Radcliffe Hospital · 0 of 1 trials Phase 2+
- Wen-Chih WuProvidence VA Medical Center · 0 of 1 trials Phase 2+
Registry trials of sapropterin updated in the last three years, counted by the country group of their listed sites. A trial with sites in several groups counts in each; 15 of 15 have all sites in one country.
Site counts are not patients per country, and trials registered only outside ClinicalTrials.gov are not covered. Where sites are is a fact about the record, not a judgement of its quality. Europe is the EU and EEA, the UK and Switzerland. 1 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
12 trials of drugs against PAH were stopped early; 2 give no reason
Terminated, withdrawn and suspended interventional trials of sapropterin, newest update first, live from ClinicalTrials.gov. Each reason is quoted exactly as the registry gives it; we do not sort reasons into safety, efficacy or business. Dates are the last registry update. Showing the 12 most recent of 12.
- withdrawn · 2024-09-03 · University of Nebraska · Sapropterin Dihydrochloride (BH4, tetrahydrobiopterin)“discontinued due to change in operating plans prior to study initiation and enrollment”
- withdrawn · 2023-12-19 · University of Massachusetts, Amherst · matched by the registry's drug synonyms“Unable to recruit due to COVID-19 pandemic”
- withdrawn · 2022-01-20 · University of Massachusetts, Worcester · Sapropterin Dihydrochloride“Study was unable to be started due to unavailability of study medication.”
- terminated · 2021-09-21 · The University of Texas Medical Branch, Galveston · matched by the registry's drug synonyms“The FDA has approved Kuvan (BH4) as a therapeutic agent for phenylketonuria”
- withdrawn · 2019-08-02 · University of California, San Diego · sapropterin“Contractual issues”
- terminated · 2018-02-22 · BioMarin Pharmaceutical · Sapropterin“Recruitment challenges”
- terminated · 2017-08-21 · Johns Hopkins University · matched by the registry's drug synonyms“We were unable to recruit any subjects into this study so no subjects completed the protocol. Therefore, we are unable to provide any conclusions.”
- terminated · 2016-04-20 · Dr. Linda Randolph · matched by the registry's drug synonyms“Participants found the study procedures to be too cumbersome and no longer wanted to participate”
- terminated · 2015-07-07 · The University of Texas Health Science Center, Houston · SapropterinNo reason given
- withdrawn · 2014-12-17 · Children's National Research Institute · sapropterin dihydrochloride“poor recruitment”
- terminated · 2014-08-28 · Emory University · matched by the registry's drug synonyms“Difficulty with recruitment and agreed with Sponsor to report completed data as case reports”
- terminated · 2007-09-20 · Orphanetics Pharma Entwicklungs GmbH · matched by the registry's drug synonymsNo reason given
Paediatric incentives and obligations for PAH's drugs
For sapropterin: what EMA and FDA publish about paediatric plans, orphan status and pediatric approvals, and how many registered studies take children. Each line is a yes, no or not published fact from the record linked under it; none of it is a forecast.
- FDA pediatric target list: no · PAH is not on the listRule: Target is on FDA's Pediatric Molecular Target List (relevant targets). Source: FDA Pediatric Molecular Target List (Listed as February 2026 on the FDA Pediatric Oncology page; the file served is 9.7.22_the_relevant_molecular_target_list.xlsx, whose Summary of Changes sheet is headed 'SEPTEMBER 2022 UPDATE' (footnote date 2022-09-01)), 2026-11-11
- EU paediatric investigation plan: yes · EMEA-001476-PIP01-13-M01 (sapropterin dihydrochloride, Treatment of hyperphenylalaninemia): PM: decision on the application for modification of an agreed PIP, 9 Sept 2016; compliance positive 10 Oct 2014Rule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA EMEA-001476-PIP01-13-M01, 2026-11-11
- EU orphan designation: yes · EU/3/05/308 withdrawn 26 Aug 2005: Treatment of hyperphenylalaninaemiaRule: An EU orphan designation lists the drug as its active substance (exact name) or belongs to a medicine that does; withdrawn and expired designations are listed with their status. Source: EMA EU/3/05/308, 2026-11-11
- Authorised in the EU: yes · Sapropterin Dipharma: authorised since 16 Feb 2022; Kuvan: authorised since 2 Dec 2008Rule: An EMA medicine record lists the drug as its active substance or INN, exact name; national-only authorisations are not in this file. Source: EMA data download (dated snapshot), 2026-11-11
- FDA orphan designation: not published · FDA's orphan designation database turns away automated requests, so this app does not read it; search it by hand at the linkRule: Would be: an FDA orphan designation names the drug. Source: FDA orphan designations search
- FDA pediatric oncology approval: no · FDA's table lists no pediatric approval of sapropterinRule: FDA's Pediatric Oncology Drug Approvals table names the drug. Source: FDA Pediatric Oncology Drug Approvals (content current as of 2026-03-03), 2026-11-12
- Registered studies open to children: yes · 29 interventional studies of sapropterin include patients under 18; 2 are recruiting, not yet recruiting or activeRule: The registry's age group includes Child (birth to 17 years), which also counts studies that set no minimum age. Source: ClinicalTrials.gov search, 2026-11-12
Rare pediatric disease voucher. FDA, content current as of 29 Apr 2026: “As of February 3, 2026, enactment of the Consolidated Appropriations Act, 2026, the rare pediatric disease PRV program will sunset after September 30, 2029. FDA may not award any PRVs under this program after September 30, 2029.” Voucher sale prices are not shown here; they appear only as company-reported news. FDA: Rare Pediatric Disease Designation and Priority Review Voucher Programs
All 2 drugs and clinical candidates as a table
Each drug, stage and indication links to its Open Targets record, where the trials and approvals behind it are listed. Salt forms (for example a mesylate) are listed as Open Targets records them, as separate entries.