FGFR4 fibroblast growth factor receptor 4
ENSG00000160867 · protein coding · Open Targets profile
Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays a role in the regulation of cell proliferation, differentiation and migration, and in regulation of lipid metabolism, bile acid biosynthesis, glucose uptake, vitamin D metabolism and phosphate homeostasis. Required for normal down- regulation of the expression of CYP7A1, the rate-limiting enzyme in bile acid synthesis, in response to FGF19. Phosphorylates PLCG1 and FRS2. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes SRC-dependent phosphorylation of the matrix protease MMP14 and its lysosomal degradation. FGFR4 signaling is down-regulated by receptor internalization and degradation; MMP14 promotes internalization and degradation of FGFR4. Mutations that lead to constitutive kinase activation or impair normal FGFR4 inactivation lead to aberrant signaling. {ECO:0000269|PubMed:11433297, ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:17311277, ECO:0000269|PubMed:17623664, ECO:0000269|PubMed:18480409, ECO:0000269|PubMed:18670643, ECO:0000269|PubMed:20018895, ECO:0000269|PubMed:20683963, ECO:0000269|PubMed:20798051, ECO:0000269|PubMed:20876804, ECO:0000269|PubMed:21653700, ECO:0000269|PubMed:7518429, ECO:0000269|PubMed:7680645, ECO:0000269|PubMed:8663044}.
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 Withdrawn means the drug was pulled from the market or from development.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 Ligand, Druggable Family
- Antibody
- GO CC high conf, UniProt loc med conf, UniProt SigP or TMHMM
- PROTAC
- UniProt Ubiquitination, Database Ubiquitination, Small Molecule Binder
- Other modalities
- Advanced Clinical
gnomAD loss of function constraint: o/e 0.7005500197410583 (upper bound 0.8640400171279907). 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 157 registry trials, updated in the last three years, of the most advanced drugs against FGFR4 (erdafitinib, nintedanib esylate, infigratinib, futibatinib, nintedanib, orantinib, derazantinib, brivanib, brivanib alaninate, aldafermin, rogaratinib, fexagratinib), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Alain C MitaECOG-ACRIN Cancer Research Group · 2 of 2 trials Phase 2+
- Julien EdelineCentre Eugène Marquis · 2 of 2 trials Phase 2+
- Manuel HäcklBasilea Pharmaceutica International Ltd, Allschwil · 2 of 2 trials Phase 2+
- Alice LeeChildren's Oncology Group · 1 of 1 trials Phase 2+
- Antoine ItalianoInstitut Bergonié · 1 of 1 trials Phase 2+
- Birgit GeoergerGustave Roussy, Cancer Campus, Grand Paris · 1 of 1 trials Phase 2+
- David van VeenhuyzenQED Therapeutics, a BridgeBio company · 1 of 1 trials Phase 2+
- Di Maria JiangUniversity Health Network Princess Margaret Cancer Center LAO · 1 of 1 trials Phase 2+
- Donald W ParsonsChildren's Oncology Group · 1 of 1 trials Phase 2+
- E.E. VoestThe Netherlands Cancer Institute · 1 of 1 trials Phase 2+
- Eugene PietzakMemorial Sloan Kettering Cancer Center · 1 of 1 trials Phase 2+
- Hearn J ChoMultiple Myeloma Research Consortium · 1 of 1 trials Phase 2+
- Ivan BorbathCliniques universitaires Saint-Luc- Université Catholique de Louvain · 1 of 1 trials Phase 2+
- Jacques BONNETERREOscar Lambret Center · 1 of 1 trials Phase 2+
- Jean-Marc NACCACHEFondation Hôpital Saint-Joseph · 1 of 1 trials Phase 2+
Registry trials of erdafitinib, nintedanib esylate, infigratinib, futibatinib, nintedanib, orantinib, derazantinib, brivanib, brivanib alaninate, aldafermin, rogaratinib, fexagratinib 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; 84 of 145 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. 12 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
66 trials of drugs against FGFR4 were stopped early; 9 give no reason
Terminated, withdrawn and suspended interventional trials of erdafitinib, nintedanib esylate, infigratinib, futibatinib, nintedanib, orantinib, derazantinib, brivanib, brivanib alaninate, aldafermin, rogaratinib, fexagratinib, 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 25 most recent of 66.
- terminated · 2026-11-10 · National Institute of Dental and Craniofacial Research (NIDCR) · matched by the registry's drug synonyms“Study was stopped early due to a greater than expected incidence of ocular AEs and analysis of the data from the first 4 subjects indicating that the likelihood of permanent remission with this therapy was low.”
- terminated · 2026-08-19 · Boundless Bio, Inc. · Futibatinib“Decision was made to halt the study based on overall clinical experience and market considerations. This decision was not driven by any safety signal.”
- terminated · 2026-03-27 · M.D. Anderson Cancer Center · Futibatinib“PI request”
- terminated · 2026-02-12 · Jennifer Lee Caswell-Jin · Infigratinib“Drug manufacturer decision to terminate development.”
- terminated · 2026-02-06 · M.D. Anderson Cancer Center · Erdafitinib“<75% participation”
- terminated · 2026-01-13 · Novartis Pharmaceuticals · matched by the registry's drug synonyms“Sponsor Decision”
- terminated · 2025-12-31 · Taiho Oncology, Inc. · Futibatinib“Sponsor decided to discontinue the study due to strategic considerations and not due to any safety-related concerns.”
- terminated · 2025-11-13 · Taiho Oncology, Inc. · Futibatinib, Futibatinib plus Fulvestrant“The Sponsor decided to discontinue the study due to strategic considerations and not due to any safety-related concerns.”
- terminated · 2025-10-24 · Nader Sanai · Infigratinib“Study drug no longer available.”
- withdrawn · 2025-10-21 · National Cancer Institute (NCI) · Erdafitinib“Feasibility issues”
- terminated · 2025-10-08 · Taiho Oncology, Inc. · Futibatinib“Sponsor made a strategic decision to terminate the study considering enrollment challenges for some of the cohorts in the trial.”
- terminated · 2025-09-19 · European Organisation for Research and Treatment of Cancer - EORTC · Nintedanib“lack of scientific relevance (change in the treatment landscape) and poor recruitment”
- terminated · 2025-09-02 · McGill University Health Centre/Research Institute of the McGill University Health Centre · Nintedanib 150 milligrams [Ofev]“Slow recruitment”
- withdrawn · 2025-05-07 · NGM Biopharmaceuticals, Inc · aldafermin“Study was terminated by the Sponsor because the FDA advised a trial design change which made it infeasible to continue the study.”
- terminated · 2025-03-06 · Boehringer Ingelheim · matched by the registry's drug synonymsNo reason given
- withdrawn · 2025-02-24 · West Virginia University · Nintedanib“Unable to enroll any subjects. IRB closed study in agreement with PI.”
- terminated · 2025-02-13 · Boehringer Ingelheim · nintedanibNo reason given
- terminated · 2025-02-07 · Taiho Oncology, Inc. · Futibatinib“Due to Poor Recruitment”
- terminated · 2025-02-03 · Boehringer Ingelheim · Nintedanib“Substance discontinued”
- terminated · 2025-02-03 · Janssen Research & Development, LLC · Erdafitinib“Mild/moderate hepatic impairment (HI) cohorts completed with no impact to erdafitinib exposure. Severe HI cohort enrollment stopped early.”
- terminated · 2025-01-01 · M.D. Anderson Cancer Center · Infigratinib“Drug manufacturer made the business decision to cease all infigratinib oncology research in the US and withdrew the IND”
- terminated · 2024-09-19 · Taiho Oncology, Inc. · Futibatinib and Binimetinib“Strategic decision by sponsor.”
- terminated · 2024-08-14 · LianBio LLC · Infigratinib“Business Reason”
- terminated · 2024-07-23 · Zai Lab (Shanghai) Co., Ltd. · MGD013 in combination with Brivanib Alaninate“Due to the rapid shifting of liver cancer disease landscape and the company's adjustment of development strategy.”
- terminated · 2024-06-18 · Novartis Pharmaceuticals · matched by the registry's drug synonyms“Sponsor decision”
Paediatric incentives and obligations for FGFR4's drugs
For erdafitinib, nintedanib esylate, infigratinib, futibatinib, nintedanib, orantinib, derazantinib, brivanib, brivanib alaninate, aldafermin, rogaratinib, fexagratinib: 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 · FGFR4 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 · EMA/PE/0000223498 (Infigratinib, Treatment of achondroplasia): PM: decision on the application for modification of an agreed PIP, 3 Jan 2025; EMEA-002042-PIP03-23 (Erdafitinib, Treatment of urothelial carcinoma): W: decision granting a waiver in all age groups for all conditions or indications, 6 May 2024; EMEA-002042-PIP02-20-M01 (Erdafitinib, Treatment of all conditions included in the category of malignant neoplasms (except urothelial carcinoma, haematopoietic and lymphoid tissue neoplasms)): PM: decision on the application for modification of an agreed PIP, 10 Jun 2022; EMEA-001006-PIP05-18-M01 (nintedanib, Treatment of fibrosing Interstitial Lung Diseases (ILD)): PM: decision on the application for modification of an agreed PIP, 29 Oct 2021; compliance positive 22 Jul 2022; +8 moreRule: An EMA PIP decision (agreement, modification or waiver) lists the drug as its active substance, exact name. Source: EMA data download (dated snapshot), 2026-11-11
- EU orphan designation: yes · EU/3/21/2475 positive 19 Jul 2021: Treatment of achondroplasia; EU/3/19/2146 withdrawn 1 Apr 2019: Treatment of biliary tract cancer; EU/3/25/3157 positive 21 Nov 2025: Treatment of hypochondroplasia; EU/3/20/2329 withdrawn 21 Aug 2020: Treatment of cholangiocarcinoma; +4 moreRule: 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 data download (dated snapshot), 2026-11-11
- Authorised in the EU: yes · Ofev: authorised since 14 Jan 2015; Nintedanib Accord: authorised since 19 Apr 2024; Balversa: authorised since 22 Aug 2024; Vargatef: authorised since 21 Nov 2014; +3 moreRule: 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 erdafitinib, nintedanib esylate, infigratinib, futibatinib, nintedanib, orantinib, derazantinib, brivanib, brivanib alaninate, aldafermin, rogaratinib, fexagratinibRule: 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 · 19 interventional studies of erdafitinib, nintedanib esylate, infigratinib, futibatinib, nintedanib, orantinib, derazantinib, brivanib, brivanib alaninate, aldafermin, rogaratinib, fexagratinib include patients under 18; 10 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 17 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.