WELIREG (belzutifan)
WELIREG is indicated for the treatment of Von Hippel-Lindau Disease; Renal Cell Carcinoma; Central Nervous System Hemangioblastoma; Pancreatic Neuroendocrine Tumor; Pheochromocytoma; Paraganglioma.
How WELIREG Works
Belzutifan is a selective inhibitor of hypoxia-inducible factor 2 alpha (HIF-2α). In healthy cells, the VHL protein facilitates the degradation of HIF-2α. In patients with VHL disease or certain renal cancers, the lack of functional VHL protein leads to the stabilization and accumulation of HIF-2α. Once stabilized, HIF-2α forms a complex with HIF-1β, acting as a transcription factor that upregulates genes associated with cellular proliferation, angiogenesis, and tumor growth. Belzutifan binds to HIF-2α, blocking its interaction with HIF-1β and thereby reducing the expression of these downstream oncogenic target genes.
Development Insights
Details
- Status
- Prescription
- First Approved
- 2021-08-13
- PDUFA Date
- 2026-06-19 (24d)
- Patent Cliff
- 2042
- Revenue
- $160M (Q4-2024)
- Routes
- ORAL
- Dosage Forms
- TABLET
WELIREG Approval History
What WELIREG Treats
6 indicationsWELIREG is approved for 6 conditions since its original approval in 2021. These indications span multiple therapeutic areas including oncology, immunology, and more.
- Von Hippel-Lindau Disease
- Renal Cell Carcinoma
- Central Nervous System Hemangioblastoma
- Pancreatic Neuroendocrine Tumor
- Pheochromocytoma
- Paraganglioma
WELIREG Boxed Warning
EMBRYO-FETAL TOXICITY Exposure to WELIREG during pregnancy can cause embryo-fetal harm. Verify pregnancy status prior to the initiation of WELIREG. Advise patients of these risks and the need for effective non-hormonal contraception. WELIREG can render some hormonal contraceptives ineffective [see Warnings and Precautions (5.3) , Drug Interactions (7.2) , Use in Specific Populations (8.1 , 8.3) ]. WARNING: EMBRYO-FETAL TOXICITY See full prescribing information for complete boxed warning. Exposur...
WARNING: EMBRYO-FETAL TOXICITY Exposure to WELIREG during pregnancy can cause embryo-fetal harm. Verify pregnancy status prior to the initiation of WELIREG. Advise patients of these risks and the need for effective non-hormonal contraception. WELIREG can render some hormonal contraceptives ineffective [see Warnings and Precautions (5.3) , Drug Interactions (7.2) , Use in Specific Populations (8.1 , 8.3) ]. WARNING: EMBRYO-FETAL TOXICITY See full prescribing information for complete boxed warning. Exposure to WELIREG during pregnancy can cause embryo-fetal harm. Verify pregnancy status prior to the initiation of WELIREG. Advise patients of these risks and the need for effective non-hormonal contraception. WELIREG can render some hormonal contraceptives ineffective. ( 5.3 , 7.2 , 8.1 , 8.3 )
WELIREG Competitive Set
ProThree rings of competition based on shared molecular targets and treated indications.
Indication competitors
Same indication, different mechanism — what else might this patient receive?
Filters applied: drops same-active-ingredient (505(b)(2) reformulations), route-mismatch (topical vs systemic), and cross-therapeutic-area matches in same-indication rings.
What's emerging in WELIREG's indications
See all emerging drugs →Phase 3 candidates targeting molecules with no FDA-approved drug, in indications WELIREG treats. First-in-class if their pivotal trials read out positive.
Drugs Similar to WELIREG
3 of 20FDA-approved drugs for similar conditions. Compare mechanisms and indications to understand treatment alternatives.
Clinical Trial Registry
33 trials| Trial | Sponsor ID | Phase | Status | Title |
|---|---|---|---|---|
| NCT07049926 | 3475-03C MK-3475-03C, 2024-516437-12-00 | Ph 1, Ph 2 | recruiting | Substudy 03C: A Study of Combination Therapies in Participants With Renal Cell Carcinoma With Recurrent Disease During or After Anti-PD-(L)1 Therapy (MK-3475-03C/KEYMAKER-U03) |
| NCT07405164 | 6482-043 U1111-1325-4582, 2025-524160-38-00 | Ph 3 | recruiting | Extension Study for Participants in Studies That Include Belzutifan (MK-6482-043/LITESPARK-043) |
| NCT07227402 LITESPARK-033 | 6482-033 U1111-1311-6892, 2024-517136-21 | Ph 3 | recruiting | A Clinical Study of Belzutifan and Zanzalintinib in People With Recurrent Kidney Cancer Following Adjuvant Therapy (MK-6482-033) |
| NCT07489495 | 6482-034 U1111-1311-4692, 2024-516993-31-00 | Ph 3 | recruiting | A Clinical Study of Belzutifan (MK-6482) and Zanzalintinib in People With Renal Cell Carcinoma (RCC) (LITESPARK-034/LS-034/MK-6482-034) |
| NCT04924075 | 6482-015 MK-6482-015, PT2977 | Ph 2 | recruiting | Belzutifan/MK-6482 for the Treatment of Advanced Pheochromocytoma/Paraganglioma (PPGL), Pancreatic Neuroendocrine Tumor (pNET), Von Hippel-Lindau (VHL) Disease-Associated Tumors, Advanced Gastrointestinal Stromal Tumor (wt GIST), or Solid Tumors With HIF-2α Related Genetic Alterations (MK-6482-015) |
| NCT04626518 | 3475-03B MK-3475-03B, KEYMAKER-U03 | Ph 1, Ph 2 | active not recruiting | Substudy 03B: A Study of Immune and Targeted Combination Therapies in Participants With Second Line Plus (2L+) Renal Cell Carcinoma (MK-3475-03B/KEYMAKER-U03) |
| NCT04626479 | 3475-03A MK-3475-03A, 2023-506838-68-00 | Ph 1, Ph 2 | active not recruiting | Substudy 03A: A Study of Immune and Targeted Combination Therapies in Participants With First Line (1L) Renal Cell Carcinoma (MK-3475-03A) |
| NCT04736706 | 6482-012 MK-6482-012, jRCT2031210435 | Ph 3 | active not recruiting | A Study of Pembrolizumab (MK-3475) in Combination With Belzutifan (MK-6482) and Lenvatinib (MK-7902), or Pembrolizumab/Quavonlimab (MK-1308A) in Combination With Lenvatinib, Versus Pembrolizumab and Lenvatinib, for Treatment of Advanced Clear Cell Renal Cell Carcinoma (MK-6482-012) |
| NCT04586231 | 6482-011 MK-6482-011, jRCT2031210311 | Ph 3 | active not recruiting | A Study of Belzutifan (MK-6482) in Combination With Lenvatinib Versus Cabozantinib for Treatment of Renal Cell Carcinoma (MK-6482-011) |
| NCT05239728 | 6482-022 MK-6482-022, LITESPARK-022 | Ph 3 | active not recruiting | A Study of Belzutifan (MK-6482) Plus Pembrolizumab (MK-3475) Versus Placebo Plus Pembrolizumab in Participants With Clear Cell Renal Cell Carcinoma Post Nephrectomy (MK-6482-022) |
| NCT06428396 | 6482-029 MK-6482-029, LITESPARK-029 | Ph 2 | recruiting | Study of Belzutifan (MK-6482) Plus Fulvestrant for ER+/HER2- Metastatic Breast Cancer (MK-6482-029/LITESPARK-029) |
| NCT03401788 | 6482-004 PT2977-202, MK-6482-004 | Ph 2 | active not recruiting | A Phase 2 Study of Belzutifan (PT2977, MK-6482) for the Treatment of Von Hippel Lindau (VHL) Disease-Associated Renal Cell Carcinoma (RCC) (MK-6482-004) |
| NCT05468697 | 6482-024 MK-6482-024, LITESPARK-024 | Ph 1, Ph 2 | active not recruiting | A Study of Belzutifan (MK-6482) in Combination With Palbociclib Versus Belzutifan Monotherapy in Participants With Advanced Renal Cell Carcinoma (MK-6482-024/LITESPARK-024) |
| NCT06234605 | HC366-RCC2311 MK-6482-030 | Ph 1 | recruiting | A Study of HC-7366 in Combination With Belzutifan (WELIREG™) in Patients With Renal Cell Carcinoma |
| NCT07187778 | 2024-1884 NCI-2025-06635 | Ph 2 | recruiting | Phase II Trial of Single Agent Belzutifan or Pembrolizumab Versus Combination as Neoadjuvant Therapy in Clear Cell Renal Cell Carcinoma (BLAZE) |
| NCT05030506 | 6482-010 MK-6482-010 | Ph 1 | active not recruiting | A Study of Belzutifan (MK-6482) as Monotherapy and in Combination With Lenvatinib (E7080/MK-7902) With or Without Pembrolizumab (MK-3475) in China Participants With Advanced Renal Cell Carcinoma (MK-6482-010) |
| NCT05899049 | 6482-012 China Extension MK-6482-012 China Extension, jRCT2031210435 | Ph 3 | active not recruiting | A Study of Pembrolizumab (MK-3475) in Combination With Belzutifan (MK-6482) and Lenvatinib (MK-7902), or Pembrolizumab/Quavonlimab (MK-1308A) in Combination With Lenvatinib, vs Pembrolizumab and Lenvatinib, for Treatment of Advanced Clear Cell Renal Cell Carcinoma (MK-6482-012)-China Extension Study |
| NCT06677190 | 24-519 | Ph 2 | recruiting | Belzutifan in Recurrent Clear Cell Carcinoma of Gynecologic Origin |
| NCT07121959 | 6482-039 MK-6482-039 | Ph 1 | completed | A Study of Belzutifan (MK-6482) and Metformin in Healthy Adult Participants (MK-6482-039) |
| NCT07179770 | 24-01254 5K12CA270377-02 | Ph 1 | recruiting | Effects of Belzutifan on 89Zr-DFO-girentuximab PET Uptake in Patients With Renal Cell Carcinoma (RCC) |
| NCT07167329 BELIEVE-VHL | ACCamargoCC | Ph 2 | recruiting | Real-World Effectiveness and Pharmacogenetics of Belzutifan in VHL Syndrome: The BELIEVE-VHL Trial |
| NCT02974738 | 6482-001 PT2977-101, MK-6482-001 | Ph 1 | active not recruiting | A Trial of Belzutifan (PT2977, MK-6482) Tablets In Patients With Advanced Solid Tumors (MK-6482-001) |
| NCT07023432 | 2025-0268 NCI-2025-04261 | Ph 2 | not yet recruiting | Belzutifan's Role in Active Surveillance Versus Treatment for Indolentmetastatic Clear Cell Renal Ccell Carcinoma (BRAVE-RCC) |
| NCT06903715 | 6482-035 CA46602 | Ph 1 | completed | A Clinical Study of Belzutifan (MK-6482) Alone or With Phenytoin in Healthy Participants (CA46602/MK-6482-035) |
| NCT04195750 results posted | 6482-005 MK-6482, 205262 | Ph 3 | active not recruiting | A Study of Belzutifan (MK-6482) Versus Everolimus in Participants With Advanced Renal Cell Carcinoma (MK-6482-005) |
| NCT04994522 results posted | 6482-021 MK-6482-021 | Ph 1 | completed | A Study of Belzutifan (MK-6482) in Participants With Renal Impairment (MK-6482-021) |
| NCT04976634 | 6482-016 MK-6482-016, 2023-503905-12-00 | Ph 2 | active not recruiting | Pembrolizumab Plus Lenvatinib in Combination With Belzutifan in Solid Tumors (MK-6482-016) |
| NCT04489771 results posted | 6482-013 MK-6482-013, 2022-502123-21-00 | Ph 2 | active not recruiting | A Study of Belzutifan (MK-6482) in Participants With Advanced Renal Cell Carcinoma (MK-6482-013) |
| NCT04995484 results posted | 6482-020 MK-6482-020 | Ph 1 | completed | A Study of Belzutifan (MK-6482) in Participants With Hepatic Impairment (MK-6482-020) |
| NCT03634540 | 6482-003 PT2977-201, MK-6482-003 | Ph 2 | active not recruiting | A Trial of Belzutifan (PT2977, MK-6482) in Combination With Cabozantinib in Patients With Clear Cell Renal Cell Carcinoma (ccRCC) (MK-6482-003) |
| NCT04846920 | 6482-018 MK-6482-018 | Ph 1 | active not recruiting | A Study of Belzutifan (MK-6482) in Participants With Advanced Clear Cell Renal Cell Carcinoma (MK-6482-018) |
| NCT03445169 | 6482-002 PT2977-103 | Ph 1 | completed | A Food Effect Study in Healthy Volunteers With Belzutifan (PT2977, MK-6482) Tablets |
| NCT07593040 Moonlanding | VHIO24002 2024-519673-18-00 | Ph 2 | not yet recruiting | Pembrolizumab Plus Belzutifan With or Without Lenvatinib in Localized Renal Cell Carcinoma |
Active Pipeline
Ongoing clinical trials by development phase
Key Completed Trials
Completed studies with published results, ranked by significance
Trial Timeline
Full development history with FDA approval milestones
Understanding FDA Approval Types
| Count | Type | What it means |
|---|---|---|
| - | ORIG | Original approval - drug first enters market |
| - | SUPPL - Efficacy | New indication (new disease/condition approved) |
| - | SUPPL - Labeling | Label text changes (warnings, dosing updates) |
| - | SUPPL - Manufacturing | Production changes (new facility) |
| - | SUPPL - Chemistry | Formulation changes (new dosage strength) |
Green lines in the timeline show ORIG and Efficacy approvals - the clinically meaningful milestones.
WELIREG FDA Label Details
Indications & Usage
FDA Label (PDF)WELIREG is indicated for the treatment of Von Hippel-Lindau Disease; Renal Cell Carcinoma; Central Nervous System Hemangioblastoma; Pancreatic Neuroendocrine Tumor; Pheochromocytoma; Paraganglioma.
WARNING: EMBRYO-FETAL TOXICITY Exposure to WELIREG during pregnancy can cause embryo-fetal harm. Verify pregnancy status prior to the initiation of WELIREG. Advise patients of these risks and the need for effective non-hormonal contraception. WELIREG can render some hormonal contraceptives ineffecti...
WELIREG Patents & Exclusivity
Patents (3 active)
Exclusivity
Pro Intelligence Preview
Deep insights for WELIREG
Revenue Insights
- • Q4-2024: $160M
- • Historical trend analysis
Patent Timeline
- • Cliff: 2042
- • 7 active patents
Trial Analysis
- • 32 total trials
- • Stage: Growth
Competitive Landscape
- • 20 similar drugs
- • Same target/indication analysis
Full approval history • All patents • Revenue trends • Competitor analysis
Data Sources
Data sourced from official FDA and NIH databases. Click links to verify on original sources.
How We Calculate These Metrics
Trial Activity Stage
Measures the current development activity pattern based on trial phases, status, and trends. Important: This measures R&D activity, not commercial lifecycle.
Trial statuses: "Active" means recruiting or ongoing. "Completed" means reached planned endpoint. "Terminated" means stopped early—often due to safety, efficacy, or business reasons.
- Growth: High proportion of early-phase trials (Phase 1/2), active development
- Expansion: Significant Phase 3 activity, approaching or pursuing approvals
- Mature: Substantial Phase 4 post-marketing studies
- Stable: Mixed phase distribution, steady development
- Declining: Low active trial ratio, reduced R&D investment