TNFSF11 TNF superfamily member 11
ENSG00000120659 · protein coding · Open Targets profile
Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy (PubMed:22664871). Induces osteoclastogenesis by activating multiple signaling pathways in osteoclast precursor cells, chief among which is induction of long lasting oscillations in the intracellular concentration of Ca (2+) resulting in the activation of NFATC1, which translocates to the nucleus and induces osteoclast-specific gene transcription to allow differentiation of osteoclasts. During osteoclast differentiation, in a TMEM64 and ATP2A2-dependent manner induces activation of CREB1 and mitochondrial ROS generation necessary for proper osteoclast generation (By similarity). {ECO:0000250|UniProtKB:O35235, ECO:0000269|PubMed:22664871}.
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
- High-Quality Ligand
- Antibody
- Approved Drug, GO CC high conf, UniProt loc med conf, UniProt SigP or TMHMM
- PROTAC
- Small Molecule Binder
gnomAD loss of function constraint: o/e 0.3729200065135956 (upper bound 0.604200005531311). 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 118 registry trials, updated in the last three years, of the most advanced drugs against TNFSF11 (denosumab), ranked by Phase 2+ trials. Live from ClinicalTrials.gov.
- Bente LangdahlAarhus University Hospital · 2 of 2 trials Phase 2+
- Chi Chiu MokTuen Mun Hospital · 2 of 2 trials Phase 2+
- Elizabeth ShaneColumbia University · 2 of 2 trials Phase 2+
- Ruth WittoekGhent Universitary Hospital · 2 of 2 trials Phase 2+
- Sam Kafai YahyaviDivision of Translational Endocrinology, Herlev, Copenhagen · 2 of 2 trials Phase 2+
- Steven C KirshblumKessler Institute for Rehabilitation · 2 of 2 trials Phase 2+
- Felicitas BulloAlvotech Swiss AG · 1 of 3 trials Phase 2+
- Adetunji T ToriolaWashington University School of Medicine · 1 of 2 trials Phase 2+
- Weibo XiaPeking Union Medical College Hospital · 1 of 2 trials Phase 2+
- Adi CohenColumbia University · 1 of 1 trials Phase 2+
- Alison M BoyceNational Institute of Dental and Craniofacial Research (NIDCR) · 1 of 1 trials Phase 2+
- Andreas MüllerKantonsspital Winterthur KSW · 1 of 1 trials Phase 2+
- Antonis GoulasSchool of Medicine, Aristotle University of Thessaloniki · 1 of 1 trials Phase 2+
- Arnoud TempletonCantonal Hospital of St. Gallen · 1 of 1 trials Phase 2+
- Athanasios D Anastasilakis424 General Military Hospital, Thessaloniki, Greece · 1 of 1 trials Phase 2+
Registry trials of denosumab 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; 90 of 113 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. 5 trials list no sites and are left out. Source: ClinicalTrials.gov, fetched live.
33 trials of drugs against TNFSF11 were stopped early; 2 give no reason
Terminated, withdrawn and suspended interventional trials of denosumab, 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 33.
- terminated · 2026-10-23 · Swiss Cancer Institute · Denosumab (reduced dosing), Denosumab (standard dosing)“Board decision as by March 2026, the number of patients undergoing treatment decreased to around 50, from the total 1,380 patients enrolled in the trial. And due to price changes in medication”
- terminated · 2026-09-08 · ETOP IBCSG Partners Foundation · Denosumab“Completion of recruitment was not feasible as accrual was slower than anticipated. Even if a benefit for denosumab could be shown, these results would be of very limited clinical impact by the time they would be available”
- terminated · 2026-04-13 · Cancer Trials Ireland · matched by the registry's drug synonyms“Insufficient accrual”
- withdrawn · 2025-05-11 · Xentria, Inc. · matched by the registry's drug synonyms“Business decision not to proceed with the study.”
- terminated · 2024-07-25 · Thomas Nickolas, MD MS · Denosumab Inj 60 mg/ml“Study lost funding”
- terminated · 2024-07-03 · Mishaela Rubin · Denosumab 60 mg/ml [Prolia]“Due to enrollment difficulties compounded by the COVID pandemic.”
- withdrawn · 2024-04-09 · Taizhou Mabtech Pharmaceutical Co.,Ltd · matched by the registry's drug synonyms“Changes in the company's production plan”
- terminated · 2024-03-15 · James J. Peters Veterans Affairs Medical Center · Denosumab (Prolia)“Study ended early due to COVID-19”
- withdrawn · 2024-02-28 · Amorphical Ltd. · matched by the registry's drug synonyms“Budget”
- terminated · 2023-08-09 · University Hospital, Montpellier · Denosumab“Modified study and new deposit in RECHMPL21_0451”
- withdrawn · 2023-03-14 · Shenzhen People's Hospital · Denosumab Only Product“no partcipants enrolled”
- terminated · 2022-12-28 · Amgen · Denosumab“The study was stopped earlier than planned due to safety concerns about high levels of calcium in the blood of the participants”
- terminated · 2022-12-20 · Amgen · Denosumab“The study was stopped earlier than planned due to safety concerns about high levels of calcium in the blood of the participants”
- terminated · 2022-11-02 · Columbia University · Denosumab“Poor enrollment”
- terminated · 2022-06-14 · National Cancer Institute (NCI) · Denosumab“it was decided that due to lack of accrual on the trial, and low potential for accruing over the near future, the trial will be shut down.”
- terminated · 2021-10-22 · Centre Leon Berard · denosumab“lack of recruitment”
- terminated · 2021-09-28 · Amgen · Denosumab“Terminated: Amgen decision following Primary Analysis. Not due to safety reason”
- terminated · 2021-01-06 · European Organisation for Research and Treatment of Cancer - EORTC · Denosumab 120 MG/1.7 ML Subcutaneous Solution [XGEVA]“Poor accrual”
- withdrawn · 2020-11-10 · University of Southern California · Denosumab“No participants enrolled in the trial”
- withdrawn · 2020-06-26 · Albert Einstein Healthcare Network · Denosumab Injection“Grant support was withdrawn from Amgen Pharmaceuticals”
- withdrawn · 2020-01-18 · Borstkanker Onderzoek Groep · Denosumab 120 mg, Denosumab 60 mg“Due to new insights”
- terminated · 2020-01-02 · Hope Rugo, MD · Denosumab“Low Accrual”
- terminated · 2019-12-12 · Hamad Medical Corporation · Denosumab 60 MG/ML Prefilled Syringe“failed to recruit eligible subjects”
- withdrawn · 2019-12-06 · Indiana University · denosumab“was not funded”
- terminated · 2019-11-22 · M.D. Anderson Cancer Center · DenosumabNo reason given
Paediatric incentives and obligations for TNFSF11's drugs
For denosumab: 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 · TNFSF11 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-000145-PIP02-12-M05 (denosumab, Treatment of osteoporosis): PM: decision on the application for modification of an agreed PIP, 14 Apr 2023; compliance positive 13 Dec 2024; EMEA-000145-PIP01-07-M09 (denosumab, Prevention of skeletal related events in patients with bone metastases;Treatment of bone loss associated with sex hormone ablative therapy;Treatment of chronic idiopathic arthritis (including rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and juvenile idiopathic arthritis);Treatment of giant cell tumour of bone;Treatment of hypercalcemia of malignancy): PM: decision on the application for modification of an agreed PIP, 16 Mar 2018; compliance positive 1 Mar 2019Rule: 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: no · No EU orphan designation names denosumabRule: 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 · Bildyos: authorised since 17 Sept 2025; Jubereq: authorised since 26 May 2025; Yaxwer: authorised since 23 Jun 2025; Prolia: authorised since 26 May 2010; +28 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: yes · Denosumab [Xgeva], 13 Jun 2013: Treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidityRule: 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 · 27 interventional studies of denosumab 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 1 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.
| Drug | Type | Highest stage | Indications | Source records |
|---|---|---|---|---|
| DENOSUMAB | Antibody | phase 4 | osteoporosis, bone disorder, giant cell tumor, bone resorption, breast cancer, bone metastasis, metastasis, hypercalcemia disease, +42 more | Open Targets · ChEMBL |