Investigational Drug Information for MK-6482

What is the drug development status for MK-6482?

MK-6482 is an investigational drug.

There have been 20 clinical trials for MK-6482. The most recent clinical trial was a Phase 1 trial, which was initiated on February 25^th 2021.

The most common disease conditions in clinical trials are Carcinoma, Renal Cell, Carcinoma, and Neoplasms. The leading clinical trial sponsors are Merck Sharp & Dohme Corp., Peloton Therapeutics, Inc., and Eisai Inc.

There are six US patents protecting this investigational drug and fifty-six international patents.

Summary for MK-6482

US Patents	6
International Patents	56
US Patent Applications	119
WIPO Patent Applications	203
Japanese Patent Applications	15
Clinical Trial Progress	Phase 1 (2021-02-25)
Vendors	40

Recent Clinical Trials for MK-6482

Title	Sponsor	Phase
A Study of Belzutifan (MK-6482) in Combination With Palbociclib Versus Belzutifan Monotherapy in Participants With Advanced Renal Cell Carcinoma (MK-6482-024)	Merck Sharp & Dohme LLC	Phase 1/Phase 2
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	Eisai Inc.	Phase 3
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	Merck Sharp & Dohme LLC	Phase 3

See all MK-6482 clinical trials

Clinical Trial Summary for MK-6482

Top disease conditions for MK-6482

Top clinical trial sponsors for MK-6482

See all MK-6482 clinical trials

US Patents for MK-6482

Drugname	Patent Number	Patent Title	Patent Assignee	Estimated Expiration
MK-6482		Compositions for use in treating pulmonary arterial hypertension	Peloton Therapeutics, Inc. (Dallas, TX)
MK-6482		Combination therapy of a HIF-2-alpha inhibitor and an immunotherapeutic agent and uses thereof	PELOTON THERAPEUTICS, INC. (Dallas, TX)
MK-6482		Combination therapy of a HIF-2-.alpha. inhibitor and an immunotherapeutic agent and uses thereof	Peloton Therapeutics, Inc. (Dallas, TX)
MK-6482		Aryl ethers and uses thereof	Peloton Therapeutics Inc
MK-6482		Aryl ethers and uses thereof	PELOTON THERAPEUTICS, INC. (Dallas, TX)
MK-6482		Aryl ethers and uses thereof	PELOTON THERAPEUTICS, INC. (Dallas, TX)

International Patents for MK-6482

Drugname	Country	Document Number	Estimated Expiration	Related US Patent
MK-6482	European Patent Office	EP3203991	2034-10-10
MK-6482	World Intellectual Property Organization (WIPO)	WO2016057242	2034-10-10
MK-6482	Argentina	AR097600	2033-09-09
MK-6482	Australia	AU2014318025	2033-09-09
MK-6482	Canada	CA2919397	2033-09-09
MK-6482	China	CN105530923	2033-09-09

Development Update and Market Projections for MK-6482 (Belzutifan)

Introduction to MK-6482 (Belzutifan)

MK-6482, also known as belzutifan and marketed as Welireg, is a novel investigational drug developed by Merck (known as MSD outside the United States and Canada). It is an oral, selective inhibitor of hypoxia-inducible factor-2 alpha (HIF-2α), a protein that plays a crucial role in regulating tissue oxygen levels and is implicated in the development of various tumors.

Clinical Development Status

FDA Designations and Approvals

• In July 2020, the FDA granted Breakthrough Therapy designation to MK-6482 for the treatment of patients with von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC)[2].
• The FDA also granted orphan drug designation for VHL disease, recognizing the drug's potential in treating a rare condition[2].
• In March 2021, the FDA accepted and granted priority review for the New Drug Application (NDA) for MK-6482 for the treatment of VHL disease-associated RCC[4].
• In August 2021, MK-6482 received its first FDA approval for patients with VHL disease who require therapy for associated renal cell carcinoma, central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNETs) but do not immediately require surgery[5].

Ongoing Clinical Trials

• MK-6482 is being evaluated in various clinical trials, including Phase 2 and Phase 3 studies for advanced clear cell renal cell carcinoma (ccRCC), gastrointestinal stromal tumor (GIST), advanced pheochromocytoma/paraganglioma (PPGL), pancreatic neuroendocrine tumor (pNET), and other solid tumors with HIF-2α related genetic alterations[1][3].
• Specific trials include a Phase 2 study in VHL-associated RCC, a Phase 3 trial in advanced RCC, and combination therapy trials with other agents like pembrolizumab and lenvatinib[1][2][4].

Therapeutic Indications

Von Hippel-Lindau Disease

• MK-6482 has shown significant promise in treating patients with VHL disease, a rare genetic condition that increases the risk of developing benign tumors and several types of cancer, including renal cell carcinoma. The drug targets the accumulation of HIF-2α, which is a result of the inactivation of the VHL tumor-suppressor protein[2][4][5].

Advanced Renal Cell Carcinoma

• The drug is also being studied in advanced RCC, both as monotherapy and in combination with other treatments. This includes trials evaluating its efficacy in previously treated patients and as a first-line treatment for advanced clear cell RCC[4].

Other Tumor Types

• MK-6482 is under investigation for various other tumor types, including metastatic castration-resistant prostate cancer (mCRPC), human epidermal growth factor receptor 2-negative (ER+/HER2-) unresectable metastatic breast cancer, pancreatic ductal adenocarcinoma, hepatocellular carcinoma, and others[3].

Market Projections

Sales Forecasts

• Evaluate Pharma forecasts $386 million in Welireg sales by 2026. However, if the drug secures additional FDA approvals for other indications, such as advanced renal cell carcinoma, it could potentially achieve annual sales between $1 billion to $1.5 billion[5].

Market Opportunity

• The FDA approval for VHL disease patients represents a meaningful first-to-market opportunity. With an estimated 10,000 VHL patients in the U.S. and 200,000 globally, the market potential is significant. Some analysts believe the actual number of U.S. cases could be higher, potentially doubling the estimated figure[5].

Pricing

• Welireg is priced at $26,400 per month before discounts and rebates, which is a significant factor in its market positioning and potential revenue[5].

Competitive Landscape

Merck's Oncology Portfolio

• The approval and ongoing development of MK-6482 strengthen Merck's expanding and diverse oncology portfolio, particularly as the company faces the patent cliff for its megablockbuster drug Keytruda in 2028[5].

Combination Therapies

• MK-6482 is being studied in combination with other therapies, such as pembrolizumab and lenvatinib, which could further enhance its market position and therapeutic efficacy[1][4].

Conclusion

MK-6482 (belzutifan) represents a significant advancement in the treatment of patients with VHL disease and other tumor types. With its FDA approvals and ongoing clinical trials, the drug is poised to make a substantial impact in the oncology market. The potential for additional approvals and the drug's performance in combination therapies will be crucial in determining its long-term market success.

Key Takeaways

• FDA Approvals: MK-6482 has received Breakthrough Therapy and orphan drug designations and has been approved for VHL disease-associated tumors.
• Clinical Trials: Ongoing trials include Phase 2 and Phase 3 studies for various tumor types, including advanced RCC and combination therapies.
• Market Potential: Forecasted sales of $386 million by 2026, with potential to reach $1 billion to $1.5 billion if additional approvals are secured.
• Pricing: Priced at $26,400 per month before discounts and rebates.
• Competitive Landscape: Strengthens Merck's oncology portfolio, particularly with the impending patent cliff for Keytruda.

FAQs

What is MK-6482 (belzutifan)?

• MK-6482, or belzutifan, is an oral, selective inhibitor of hypoxia-inducible factor-2 alpha (HIF-2α), used in the treatment of various tumors, particularly those associated with von Hippel-Lindau disease.

What FDA designations has MK-6482 received?

• MK-6482 has received Breakthrough Therapy designation and orphan drug designation from the FDA for the treatment of VHL disease-associated renal cell carcinoma.

What is the current market forecast for MK-6482?

• Evaluate Pharma forecasts $386 million in sales by 2026, with potential to reach $1 billion to $1.5 billion if additional FDA approvals are secured.

How is MK-6482 being studied in combination therapies?

• MK-6482 is being evaluated in combination with other therapies such as pembrolizumab and lenvatinib for the treatment of advanced clear cell renal cell carcinoma and other tumor types.

What is the pricing strategy for MK-6482?

• MK-6482 is priced at $26,400 per month before discounts and rebates.

How does MK-6482 fit into Merck's oncology portfolio?

• The approval and ongoing development of MK-6482 strengthen Merck's expanding and diverse oncology portfolio, particularly as the company faces the patent cliff for its megablockbuster drug Keytruda in 2028.

Sources

1. ClinicalTrials.gov: Various clinical trials for MK-6482.
2. Merck: FDA Grants Breakthrough Therapy Designation to Merck’s Novel HIF-2α Inhibitor MK-6482.
3. Pharmaceutical Technology: Belzutifan by Merck for Metastatic Castration-Resistant Prostate Cancer.
4. Merck: Merck Receives Priority Review From FDA for New Drug Application for HIF-2α Inhibitor Belzutifan (MK-6482).
5. Fierce Pharma: Belzutifan scores FDA nod in cancers spurred by rare disease.