RegulationBreakthrough Therapy (United States), Accelerated Approval (United States), Orphan Drug (United States), Priority Review (China), Orphan Drug (South Korea), Orphan Drug (Australia), Conditional marketing approval (European Union), Priority Review (United States)

Structure/Sequence

Molecular FormulaC17H12F3NO4S

InChIKeyLOMMPXLFBTZENJ-ZACQAIPSSA-N

CAS Registry1672668-24-4

Clinical Trials associated with Belzutifan

NCT06903715

/ Active, not recruitingPhase 1

An Open-Label, Phase 1 Study to Characterize the Effects of Phenytoin on the Pharmacokinetics of Belzutifan in Healthy Adult Participants

Researchers designed belzutifan, the study medicine, to treat certain kinds of cancer.
The goal of this study is to learn what happens to belzutifan in a healthy person's body over time when taken, by mouth, as a tablet. Researchers will learn what happens when belzutifan is taken alone and when it is taken after several days of treatment with phenytoin.

Start Date28 Mar 2025

Sponsor / Collaborator

Merck Sharp & Dohme LLC

NCT06677190

/ RecruitingPhase 2IIT

A Phase II Trial of Belzutifan in Patients with Recurrent or Persistent Clear Cell Carcinoma of the Ovary

The purpose of this research study is to see if the study drug Belzutifan is effective and safe for participants with ovarian cancer.
The name of the study drug involved in this study is:
- Belzutifan (a type of Hypoxia-Inducible Factor-2 alpha (HIF-2a) inhibitor)

Start Date01 Dec 2024

Sponsor / Collaborator

Dana-Farber Cancer Institute, Inc.

[+1]

NCT06428396

/ RecruitingPhase 2

A Phase 2, Randomized, Active-controlled, Open-label, Multicenter Study of Belzutifan Plus Fulvestrant in Participants With Estrogen Receptor Positive, HER2 Negative Unresectable Locally Advanced or Metastic Breast Cancer After Progression on Previous Endocrine Therapy (LITESPARK-029)

The purpose of this study is to assess the efficacy and safety of belzutifan (MK-6482) plus fulvestrant compared to everolimus plus endocrine therapy (ET) (investigator's choice of fulvestrant or exemestane) in adults with estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2-) unresectable metastatic breast cancer. There is no formal hypothesis testing in this study.

Start Date27 Nov 2024

Sponsor / Collaborator

Merck Sharp & Dohme LLC

100 Clinical Results associated with Belzutifan

100 Translational Medicine associated with Belzutifan

100 Patents (Medical) associated with Belzutifan

184

Literatures (Medical) associated with Belzutifan

01 Jul 2025·Translational Oncology

Targeting EPAS-1/HIF-2α Pathway to Address Endocrine Resistance in Luminal A Type Breast Cancer

Article

Author: Agarwal, Neeraj Manvi ; Choi, Junjeong ; Luo, Enzhi ; Lee, Seongmin

BACKGROUND:

Tamoxifen is most often used as the first treatment for luminal A breast cancer; however, one-third of the patients are resistant to it. Numerous studies have shown that hypoxia contributes to drug resistance and is related to poor clinical outcomes. Despite this, little is known regarding the key hypoxic mediators involved in tamoxifen resistance.

METHODS:

We performed a comprehensive multi-omics analysis using publicly available transcriptomics and whole-exome sequencing data from tamoxifen-sensitive and tamoxifen-resistant luminal A breast cancer patient samples. EPAS1 was identified as a key hypoxic mediator linked to endocrine resistance in luminal A breast cancer. In vitro assays, including Western blotting, hypoxia detection assays, and CCK8 assays, were conducted to validate the association between EPAS1 expression and tamoxifen resistance in cell lines. Additionally, we tested the effect of PT2977 (Belzutifan), an EPAS1 inhibitor, as a potential treatment for tamoxifen resistance using tamoxifen-resistant and control cells, followed by validation in xenograft models of tamoxifen-resistant tumours.

RESULTS:

Patient and cell line data revealed that EPAS1 is significantly upregulated in tamoxifen-resistant luminal A breast cancer, which is associated with poor survival outcomes and an altered tumour microenvironment. Further investigation using tamoxifen-resistant cell lines confirmed elevated EPAS1 expression levels. In vitro treatment with the EPAS1 inhibitor PT2977 resulted in a significant decrease in cell viability and modulated hypoxia-related pathways, indicating a potential therapeutic effect. Furthermore, in vivo studies showed that PT2977 reduced the growth of tamoxifen-resistant cells under the experimental conditions used.

CONCLUSION:

This study suggests that PT2977, by targeting the hypoxic gene EPAS1, has the potential to inhibit the growth of tamoxifen-resistant luminal A breast cancer. However, while PT2977 demonstrated effectiveness in reducing tumour growth under the experimental conditions used, further studies are necessary to evaluate its role in overcoming hormone resistance and to explore its therapeutic applicability in broader clinical settings and other cancer subtypes.

01 Jun 2025·American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting

Emerging Paradigms in Genitourinary Cancers: Integrating Molecular Imaging, Hypoxia-Inducible Factor–Targeted Therapies, and Antibody-Drug Conjugates in Renal Cell and Urothelial Carcinomas

Review

Author: Hofman, Michael S. ; Wulff-Burchfield, Elizabeth M. ; Eapen, Renu ; McKay, Rana R.

Novel approaches in molecular imaging and targeted therapeutics are transforming the management of renal cell carcinoma (RCC) and urothelial carcinoma (UC). This review focuses on three key areas of innovation: molecular imaging, hypoxia-inducible factor-2α (HIF-2α) inhibition, and antibody-drug conjugates (ADCs). In molecular imaging, prostate-specific membrane antigen positron emission tomography/computed tomography has shown promise in RCC, while novel tracers targeting carbonic anhydrase IX and nectin-4 are emerging for RCC and UC, respectively. These approaches may enable better characterization of disease and treatment response monitoring. HIF-2α inhibition represents a breakthrough in targeting the fundamental pathobiology of clear cell RCC, with belzutifan demonstrating significant clinical benefit in both von Hippel-Lindau disease and sporadic RCC. Next-generation HIF-2α inhibitors, including casdatifan, show promising early clinical results with distinct pharmacologic properties. ADCs have become a cornerstone of UC treatment, with enfortumab vedotin plus pembrolizumab now approved as first-line therapy. Multiple human epidermal growth factor receptor 2 (HER2)-directed ADCs have shown efficacy in HER2-expressing UC, including trastuzumab deruxtecan, which recently received tumor-agnostic approval. While ADC development in RCC faces unique challenges, novel approaches including immunostimulatory payloads and bispecific antibodies are being explored. The integration of these advances in molecular imaging and therapeutics offers opportunities for more personalized treatment approaches in RCC and UC.

01 Jun 2025·Clinical Genitourinary Cancer

CDK4/6 Inhibition With Abemaciclib in Patients With Previously Treated Advanced Renal Cell Carcinoma

Article

Author: Xu, Wenxin ; Kaelin, William G ; McGregor, Bradley A ; Choueiri, Toni K ; McDermott, David ; Xie, Wanling ; Berg, Stephanie A ; Signoretti, Sabina ; Viswanathan, Srinivas R

BACKGROUND:

Preclincal data provide a rationale for cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors alone and in combination with HIF-2α inhibitors in treatment of clear cell renal cell carcinoma (ccRCC), with randomized phase 2 clinical trials currently open exploring the combination of palbociclib with belzutifan vs belzutifan in treatment resistant ccRCC (NCT05468697). However, single agent activity for CDK4/6 inhibitors in ccRCC has not been reported. In this multi-center phase 1b clinical trial (NCT04627064), we investigated the safety and efficacy of monotherapy with abemaciclib, an oral CDK4/6 inhibitor in patients with advanced pretreated RCC.

METHODS:

Adult patients with advanced RCC with a clear cell component and ECOG status of ≤ 2 progressing after at least 1 prior regimen including immunotherapy and a VEGFR TKI received abemaciclib 200 mg twice daily in 4-week cycles until progression or unacceptable toxicity. The primary objective was to evaluate the objective response rate (ORR) of abemaciclib with a secondary endpoint of safety. First imaging was performed after 8 weeks or 2 cycles. Response was assessed per RECIST 1.1 and toxicity graded per CTCAE v5.0.

RESULTS:

Eleven patients were enrolled between December 31, 2020 and October 03, 2023. Median age was 62 years (range 54-68); 73% (n = 8) had IMDC intermediate risk disease and 1 patient had translocation RCC with a clear cell component. Median number of prior therapies was 4 (range 1-9). ORR was 0% (0/11; 8 progressive disease, 1 stable disease stopping for clinical progression, 2 not evaluable with clinical progression). About 27% (n = 3) experienced grade ≥3 treatment-related adverse events (diarrhea n = 1, nausea n = 1, neutropenia n = 1).

CONCLUSION:

In patients with heavily pretreated metastatic RCC, abemaciclib monotherapy had no clinically meaningful activity without new toxicity signals. This data will offer important insight into interpretation of results for ongoing trials exploring CDK4/6 inhibition in combination with HIF-2α inhibitors and immunotherapy.

105

News (Medical) associated with Belzutifan

19 hours ago

·www.prnewswire.com

Merck's WELIREG Entry Brings New Momentum to Pheochromocytomas and Paragangliomas Therapeutics Market | DelveInsight

The FDA has granted a third approval for WELIREG, authorizing its use as a treatment for patients with rare endocrine system tumors known as pheochromocytoma or paraganglioma (PPGL). This approval applies to individuals aged 12 and older with locally advanced, unresectable, or metastatic PPGL, making WELIREG the first oral therapy available for advanced cases of the disease. LAS VEGAS, May 28, 2025 /PRNewswire/ -- Pheochromocytomas and paragangliomas (PCPG) are highly vascular neuroendocrine tumors originating from chromaffin cells of the adrenal medulla or from neural crest-derived cells located outside the adrenal glands. These tumors are categorized based on their location, either in the adrenal medulla or in extra-adrenal paraganglia. They arise from sympathetic tissues found in the adrenal glands or along the abdomen, or from parasympathetic tissues in areas such as the head, neck, and thorax. Sympathetic tumors often secrete large quantities of catecholamines and are found in the adrenal medulla in about 80% of cases. The remaining 20% are extra-adrenal, typically located along the prevertebral and paravertebral sympathetic ganglia in the chest, abdomen, or pelvis. In 2024, there were 4,900 incident PCPG cases across the 7MM, with numbers expected to rise in the coming years. Although significant progress has been made in understanding these tumors, accurately predicting their malignancy remains challenging in the absence of detectable metastases. Surgical resection remains the primary treatment for most localized PCPGs when feasible. In cases of advanced or metastatic disease, management typically involves symptom control using medications such as alpha-blockers, beta-blockers, and inhibitors of catecholamine synthesis to avoid serious complications. When surgery is not viable, treatment options include systemic chemotherapy with Cyclophosphamide, Vincristine, and Dacarbazine (CVD), as well as radiolabeled MIBG therapy ( AZEDRA, which was approved in 2018 but discontinued in early 2024). However, the effectiveness of CVD in improving overall survival is unclear, as most patients eventually face disease progression and death. Learn more about the PCPG treatment @ New Treatment for Pheochromocytomas and Paragangliomas DEMSER (metyrosine) was authorized for use in the United States in 1979 to treat pheochromocytoma. This FDA-approved drug is indicated for preoperative preparation, treatment of patients who are not candidates for surgery, and long-term management of malignant pheochromocytoma. In January 2019, ONO gained approval in Japan to produce and sell DEMSER capsules aimed at controlling catecholamine excess in pheochromocytoma patients. Later, in July 2020, the US FDA approved the first generic version of DEMSER oral capsules, manufactured by Amneal Pharmaceuticals, marking the initial generic approval for DEMSER in the US. In May 2025, Merck announced that the FDA approved WELIREG, the company's oral inhibitor of hypoxia-inducible factor-2 alpha (HIF-2α), for treating adults and children aged 12 and older with locally advanced, inoperable, or metastatic pheochromocytoma or paraganglioma (PPGL). The approval was based on findings from the LITESPARK-015 clinical trial, a single-arm study in which the primary measure of efficacy was the objective response rate (ORR). The trial included 72 patients in a single group (Cohort A1) with measurable disease confirmed by blinded independent central review (BICR) per RECIST v1.1. All participants had a histopathological diagnosis of PPGL and either locally advanced or metastatic disease not suitable for surgical or curative treatment. Their blood pressure was adequately controlled (below 150/90 mm Hg for adults and below 135/85 mm Hg for adolescents) without recent changes in antihypertensive therapy. Patients with carcinomatous meningitis were excluded. Participants received WELIREG at 120 mg once daily until disease progression or the onset of unacceptable toxicity. The primary efficacy endpoint was ORR as assessed by BICR under RECIST v1.1 criteria. Secondary endpoints included duration of response and time to initial response. WELIREG's prescribing information includes a boxed warning noting that exposure during pregnancy may cause harm to the fetus. Healthcare providers are advised to confirm pregnancy status before starting treatment and to counsel patients on the importance of using effective non-hormonal contraception, as WELIREG can reduce the effectiveness of hormonal methods. Additionally, the drug may lead to severe anemia requiring blood transfusions and serious hypoxia, which could necessitate treatment discontinuation, supplemental oxygen, or hospitalization. Regular monitoring for anemia is recommended before and during therapy. Find out more on FDA-approved PCPG drugs @ Pheochromocytomas and Paragangliomas Treatment Options Ongoing clinical trials are assessing a range of targeted therapies aimed at improving treatment outcomes for PCPG. These include radionuclide therapies using SSTR2 agonists and antagonists, alpha-emitting agents, and SSTR2 analogs. Other approaches under investigation involve Dopamine Receptor D2 (DRD2) modulators and ClpP agonists. Each therapy employs distinct mechanisms of action, offering promising advantages and making them key candidates in the advancing PCPG therapeutic landscape. Radionuclide therapy works by delivering radiolabeled peptides to tumor cells via specific receptor targeting. Current clinical guidelines suggest that radioligand therapy may serve as a suitable first-line treatment for patients with slowly to moderately progressive metastatic PCPG, provided the tumor demonstrates uptake of the relevant radioisotope. Several prominent institutions, including the National Cancer Institute (NCI), M.D. Anderson Cancer Center, Gustave Roussy Cancer Campus, and Columbia University are actively conducting clinical studies in this area. Discover which therapies are expected to grab major PCPG market share @ Pheochromocytomas and Paragangliomas Market Report Some of the drugs in the pipeline include ONC201 (Jazz Pharmaceuticals/Chimerix), [212Pb]VMT-α-NET (Perspective Therapeutics), and LUTATHERA (Lutetium [177Lu] oxodotreotide/dotatate) (Novartis), among others. ONC201, also known as dordaviprone, is a first-in-class small-molecule imipridone that specifically targets the G-protein-coupled receptor DRD2 and the mitochondrial protease ClpP. It was investigated in a Phase II, open-label, investigator-initiated trial at the Cleveland Clinic, involving 30 patients with rare neuroendocrine tumors. Interim results demonstrated a 50% overall response rate (ORR) in paraganglioma cases with dopamine-secreting tumors located outside the brain. These findings, based on investigator assessments, were presented at the 2021 ASCO Annual Meeting and later published in Clinical Cancer Research in 2022. [212Pb] VMT-α-NET is a Targeted Alpha Therapy (TAT) radiopharmaceutical in clinical development for diagnosing and treating SSTR2-positive neuroendocrine tumors, a challenging and uncommon cancer type. Perspective Therapeutics is conducting a multicenter, open-label Phase I/IIa dose-escalation and expansion trial (NCT05636618) in patients with unresectable or metastatic SSTR2-expressing tumors who have not previously received peptide receptor radionuclide therapy. The FDA has granted Fast Track Designation (FTD) for this program based on encouraging preclinical data, regardless of patients' prior treatment history. As of February 2025, 30 patients have been enrolled in Cohort 2, with regulatory alignment pending for Cohort 3. In April 2025, Perspective Therapeutics announced that data from both the [212Pb] VMT-α-NET and [212Pb] VMT01 programs had been accepted for presentation at the upcoming ASCO Annual Meeting, scheduled for May 30–June 3, 2025, in Chicago, Illinois. Details for regular abstracts are expected to be released on May 22, 2025, at 5:00 PM EDT. Discover more about drugs for PCPG in development @ Pheochromocytomas and Paragangliomas Clinical Trials The anticipated launch of these emerging therapies for PCPG are poised to transform the market landscape in the coming years. As these cutting-edge therapies continue to mature and gain regulatory approval, they are expected to reshape the PCPG market landscape, offering new standards of care and unlocking opportunities for medical innovation and economic growth. DelveInsight estimates that the market size for PCPG is expected to grow from USD 310 million in the 7MM in 2024 at a significant CAGR by 2034. Increasing awareness and improved detection rates are contributing to a rising patient pool. Additionally, ongoing research and development of novel treatment options, including precision medicine approaches, are fueling market expansion. The growing prevalence of these rare neuroendocrine tumors, coupled with supportive healthcare infrastructure, further boosts market opportunities worldwide. DelveInsight's latest published market report, titled as Pheochromocytomas and Paragangliomas Market Insight, Epidemiology, and Market Forecast – 2034 , will help you to discover which market leader is going to capture the largest market share. The report provides comprehensive insights into the PCPG country-specific treatment guidelines, patient pool analysis, and epidemiology forecast to help understand the key opportunities and assess the market's underlying potential. The PCPG market report proffers epidemiological analysis for the study period 2020–2034 in the 7MM segmented into: Incident Cases of PCPG Occurrence or Absence of mutation in PCPG Age-specific Cases of PCPG Stage-specific Cases of PCPG The report provides an edge while developing business strategies by understanding trends shaping and driving the 7MM PCPG market. Highlights include: 10-year Forecast 7MM Analysis Epidemiology-based Market Forecasting Historical and Forecasted Market Analysis upto 2034 Emerging Drug Market Uptake Peak Sales Analysis Key Cross Competition Analysis Industry Expert's Opinion Access and Reimbursement Download this PCPG market report to assess the epidemiology forecasts, understand the patient journeys, know KOLs' opinions about the upcoming treatment paradigms, and determine the factors contributing to the shift in the PCPG market. Also, stay abreast of the mitigating factors to improve your market position in the PCPG therapeutic space. Related Reports Familial Chylomicronemia Syndrome Market Nontuberculous Mycobacterial Infection Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key FCS companies, including Ionis Pharmaceuticals Inc., Akcea Therapeutics, Novartis Pharmaceuticals, Arrowhead Pharmaceuticals, UniQure Biopharma B.V., among others. Familial Chylomicronemia Syndrome Pipeline Familial Chylomicronemia Syndrome Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key FCS companies, including Ionis Pharmaceuticals, Pfizer, Arrowhead Pharmaceuticals, Lipigon Pharmaceuticals, among others. Hypertriglyceridemia Market Hypertriglyceridemia Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key hypertriglyceridemia companies, including Arrowhead Pharmaceuticals, Mochida Pharmaceutical, Ionis Pharmaceuticals, 89bio, Regeneron Pharmaceuticals, Acasti Pharma Inc., Staten Biotechnology BV, NorthSea Therapeutics B.V., Afimmune, Rivus Pharmaceuticals, Novo Nordisk, Viking Therapeutics, Liminal BioSciences, Matinas BioPharma, Arbutus Biopharma, Better Therapeutics, among others. Hypertriglyceridemia Pipeline Hypertriglyceridemia Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key hypertriglyceridemia companies, including NorthSea Therapeutics, Arrowhead Pharmaceuticals, Zhejiang Doer Biologics, Ionis Pharmaceuticals, Inc., GeneCradle, MediciNova, Regeneron Pharmaceuticals, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Clinical ResultFast TrackDrug ApprovalPhase 2

27 May 2025

·www.einpresswire.com

HiberCell Announces Successful Completion of Dose Escalation and Enrollment Update for Ph1b Study Evaluating HC-7366 in Combination with WELIREG® (belzutifan) in Advanced ccRCC

BOSTON, May 27, 2025 (GLOBE NEWSWIRE) -- HiberCell, Inc., a clinical-stage biotechnology company developing therapeutics to address cancer relapse, metastasis, and resistance, today announced the successful completion of the dose escalation portion of its Phase 1b study evaluating HC-7366—an activator of the integrated stress response (ISR) kinase GCN2—in combination with Merck’s (known as MSD outside the US and Canada) oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, WELIREG ® (belzutifan) for the treatment of advanced clear cell renal cell carcinoma (ccRCC). The dose escalation phase enrolled 18 patients and was designed to evaluate the safety, tolerability, and pharmacokinetics (PK) of HC-7366 and to identify the recommended doses for expansion. Three dose levels of HC-7366 (20 mg, 40 mg, 60 mg) were assessed in combination with fixed-dose belzutifan (120 mg orally, once daily). All three dose levels tested cleared the respective dose-limiting toxicity (DLT) evaluations. Based on the favorable safety and PK/PD profile, the 40 mg and 60 mg doses of HC-7366 were selected for further evaluation in combination with belzutifan. HiberCell also announced that enrollment in the 40 mg expansion cohort is now complete. Enrollment for the 60 mg cohort is ongoing and is expected to complete before the end of the second quarter of 2025. Each expansion cohort is designed to enroll 15 patients. In parallel, a separate cohort evaluating HC-7366 as monotherapy at the 60 mg dose is also actively enrolling patients. “We’re pleased to announce the successful completion of the dose escalation phase of our trial, a key milestone in establishing the safety of combining HC-7366 with belzutifan,” said Steven Gillis, Ph.D., Chairman and Acting CEO of HiberCell. “We’re encouraged by the strong pace of enrollment and we’re grateful to the clinical sites, investigators, and patients participating in the study. We look forward to assessing additional safety, PK/PD, and preliminary efficacy data from the expansion cohorts, particularly as the 40 mg and 60 mg doses have been identified as the most likely to demonstrate efficacy based on preclinical models.” HiberCell is continuing to advance its understanding of HC-7366’s mechanism of action and recently presented a poster at the American Association for Cancer Research (AACR) Annual Meeting titled “In Vivo Tumor Growth Control by General Control Nonderepressible 2 (GCN2) Targeting Agents Results from Kinase Activation,” highlighting that activation of the GCN2 pathway is associated with enhanced anti-tumor activity across multiple preclinical models. WELIREG ® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. About HC-7366 HC-7366 is a first-in-class, first-in-human, selective, potent, small molecule activator of the general control nonderepressible 2 (GCN2) kinase. GCN2 is one of the kinases of the integrated stress response (ISR) family, which responds to amino acid deprivation and is a key metabolic stress sensor in cells. While cancer cells utilize the ISR for survival, prolonged or hyperactivation of GCN2 with HC-7366 has been shown to have antitumor and immunomodulatory activity as a monotherapy and in combination with SOC agents in preclinical models of both solid and liquid tumors. HC-7366 is currently under clinical development in a Phase 1b study in clear cell renal cell carcinoma in combination with belzutifan. About HiberCell HiberCell is a clinical stage oncology company, dedicated to the advancement of first-in-class agents with the novel MOA of modulation of adaptive stress pathways. We believe that therapeutic modulation of these mechanisms allows us to address tumor metastasis, treatment resistance, and cancer relapse; all significant drivers of cancer-related deaths. Our GCN2 activator, HC-7366, is currently under investigation in two Phase 1b trials in renal cell carcinoma (RCC) and acute myeloid leukemia (AML). Meanwhile, our PERK inhibitor, HC-5404 is advancing into Phase 1b development. For more information about HiberCell, please visit hibercell.com. For Media/Investor Inquiries: IR@hibercell.com Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.

Phase 1AACRClinical Result

21 May 2025

·pmlive.com

Merck’s Welireg granted FDA approval to treat rare tumour types PPGL

Merck & Co – known as MSD outside of the US and Canada – has announced that its Welireg (belzutifan) has been approved by the US Food and Drug Administration (FDA) as the first oral therapy for pheochromocytoma or paraganglioma (PPGL), two rare tumour types. The drug has been specifically authorised to treat adult and paediatric patients aged 12 years and older with locally advanced, unresectable or metastatic PPGL. Up to 2,000 new cases of PPGL, sometimes referred to as pheo par, are diagnosed in the US every year. Pheochromocytoma forms in the adrenal gland, while paraganglioma forms outside it, and both can be caused by genetic syndromes or mutations. Merck gained access to Welireg in 2019 through its $1.1bn buyout of Peloton Therapeutics. The drug is designed to inhibit the transcription factor hypoxia-inducible factor 2 alpha (HIF-2α), which regulates cellular proliferation, angiogenesis and tumour growth, and is already approved in the US for certain patients with von Hippel-Lindau (VHL) disease and renal cell carcinoma (RCC). The FDA’s latest decision was supported by results from the phase 2 LITESPARK-015 trial, which enrolled 72 patients in a single cohort who had measurable disease, a documented histopathological PPGL diagnosis, and locally advanced or metastatic disease that was not amenable to surgery or curative treatment. The objective response rate in Welireg-treated patients was 26% and median duration of response was 20.4 months. Additionally, among patients on baseline antihypertensive medications, 32% experienced a reduction in at least one antihypertensive medication by 50% or more for a minimum of six months. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories, said: “For patients with advanced PPGL, there has been a lack of approved systemic treatment options available to help manage their disease, underscoring the importance of this approval in the US.” The decision comes just three months after the European Commission granted conditional approval to Welireg for VHL disease and RCC. “The approval of Welireg in the EU introduces the first and only systemic treatment option for adult patients with certain VHL disease-associated tumours for whom localised procedures are unsuitable, and offers a new option for adult patients with advanced clear cell RCC that progressed following a PD-1 or PD-L1 inhibitor and at least two VEGF targeted therapies,” Green noted at the time.

Clinical ResultDrug ApprovalPhase 2

100 Deals associated with Belzutifan

External Link

KEGG	Wiki	ATC	Drug Bank
D11954	-	-	DB15463

R&D Status

Approved

10 top approved records.

to view more data

Indication	Country/Location	Organization	Date
Paraganglioma	United States	Merck & Co., Inc.	14 May 2025
Pheochromocytoma	United States	Merck & Co., Inc.	14 May 2025
Advanced Renal Cell Carcinoma	United States	Merck & Co., Inc.	14 Dec 2023
Hemangioblastoma	Australia	Merck Sharp & Dohme (Australia) Pty Ltd.	22 Dec 2022
Neuroendocrine tumor of pancreas	Australia	Merck Sharp & Dohme (Australia) Pty Ltd.	22 Dec 2022
Renal Cell Carcinoma	Canada	Merck Canada, Inc.	11 Jul 2022
Von Hippel-Lindau Disease	United States	Merck Sharp & Dohme Corp.	13 Aug 2021

Developing

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Locally Advanced Clear Cell Renal Cell Carcinoma	NDA/BLA	European Union	Merck & Co., Inc.	12 Dec 2024
Ovarian clear cell carcinoma	Phase 2	United States	Merck Sharp & Dohme LLC	01 Dec 2024
ER-positive/HER2-negative Breast Cancer	Phase 2	United States	Merck Sharp & Dohme LLC	27 Nov 2024
ER-positive/HER2-negative Breast Cancer	Phase 2	Argentina	Merck Sharp & Dohme LLC	27 Nov 2024
ER-positive/HER2-negative Breast Cancer	Phase 2	Canada	Merck Sharp & Dohme LLC	27 Nov 2024
ER-positive/HER2-negative Breast Cancer	Phase 2	Chile	Merck Sharp & Dohme LLC	27 Nov 2024
ER-positive/HER2-negative Breast Cancer	Phase 2	Colombia	Merck Sharp & Dohme LLC	27 Nov 2024
ER-positive/HER2-negative Breast Cancer	Phase 2	Taiwan Province	Merck Sharp & Dohme LLC	27 Nov 2024
ER-positive/HER2-negative Breast Cancer	Phase 2	Thailand	Merck Sharp & Dohme LLC	27 Nov 2024
ER-positive/HER2-negative Breast Cancer	Phase 2	United Kingdom	Merck Sharp & Dohme LLC	27 Nov 2024

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04195750 (6482-005 \| LITESPARK-005, CTgov)	Phase 3	Advanced Renal Cell Carcinoma	755	Belzutifan (Belzutifan)	ucmtgquvsl(hwuqskkkgv) = fpowsdyowi yhpootderv (fxivwpbwqt, qlbngmxwto - rpywoxkbfd) View more	-	29 Apr 2025
				Everolimus (Everolimus)	ucmtgquvsl(hwuqskkkgv) = yxyrxhczpd yhpootderv (fxivwpbwqt, cnsejoivrn - ljznslinzb) View more
P4-6.019 (AAN2025)	Not Applicable	Von Hippel-Lindau Disease VHL tumor suppressor gene \| HIF-2α	1	Belzutifan 120mg	xxorpgpgqs(deajqumcmq) = shqlvzglxm vpfptlojox (nxisjzmkvh )	Positive	07 Apr 2025
NCT04994522 (MK-6482-021, CTgov)	Phase 1	Kidney Failure, Chronic	14	Belzutifan	gvqntcorjp(pxeydivkzv) = yngpammupr hgbajinutv (yhufobpqvy, 41.4) View more	-	06 Apr 2025
NCT04924075 (LITESPARK-015, ASCO_GU2025) Manual	Phase 2	Neuroendocrine tumor of pancreas \| Renal Cell Carcinoma \| Hemangioblastoma ... View more	23	Belzutifan (RCC)	itqswhvsoq(huvbcpdifw) = mspxyojjub yisomfjunl (xbqlqggtij, 59 - 96) View more	Positive	13 Feb 2025
				Belzutifan (central nervous system [CNS]-hemangioblastomas [HBs] (Solid))	itqswhvsoq(huvbcpdifw) = ntouqpyqfi yisomfjunl (xbqlqggtij, 95 - 59) View more
NCT04195750 (LITESPARK-005, ASCO_GU2025) Manual	Phase 3	Renal Cell Carcinoma	-	Belzutifan 120 mg QD (Bone mets, yes)	bosaayvlxs(oswcpbwvid) = bzimafnbos lewxvldzxk (zlkmsoetnk ) View more	Positive	13 Feb 2025
				Everolimus 10 mg QD (Bone mets, yes)	bosaayvlxs(oswcpbwvid) = ywebciwius lewxvldzxk (zlkmsoetnk ) View more
NCT03634540 (LITESPARK-003, ASCO_GU2025) Manual	Phase 2	Renal Cell Carcinoma	102	Belzutifan 120 mg + Cabozantinib 60 mg (patients with no prior systemic therapy)	comjxmovpn(sxqmnqfjsi) = fmmwbrqvdh hpmkebqrgr (ptuzxapgmw, 55 - 82) View more	Positive	13 Feb 2025
				Belzutifan 120 mgBelzutifan 120 mg + CabozantinibCabozantinib 60 mg (patients who had received prior immunotherapy and ≤2 systemic regimens)	comjxmovpn(sxqmnqfjsi) = xscedblsrx hpmkebqrgr (ptuzxapgmw, 19 - 45) View more
ASCO_GU2025	Not Applicable	Familial Renal Cell Carcinoma HIF-2a	-	belzutifan (sporadic renal cell carcinoma (spRCC))	maryvavamo(ighwrskrdj) = nnyqasrkdc udpfkzeitw (rxspiasscf ) View more	-	13 Feb 2025
				belzutifan (VHL-syndrome-associated renal cell carcinoma (VHL-RCC))	maryvavamo(ighwrskrdj) = zvnefpspef udpfkzeitw (rxspiasscf ) View more
NCT04995484 (MK-6482-020, CTgov)	Phase 1	Liver Injury	17	Belzutifan (Moderate Hepatic Impairment)	rfrmwpvdet(ekipyikwan) = cslvwzzszr mwrgbjkkry (cjsanyhung, 80.3) View more	-	13 Jan 2025
				Belzutifan (Healthy)	rfrmwpvdet(ekipyikwan) = qsqvegbghp mwrgbjkkry (cjsanyhung, 35.1) View more
NCT03634540 (LITESPARK-003, Pubmed \| Lancet Oncol)	Phase 2	Locally Advanced Clear Cell Renal Cell Carcinoma First line	50	Belzutifan 120 mg + Cabozantinib 60 mg	tpssmzfdbo(dxmhjkbyvj) = ssmyekysff vvkjukmmot (dctcenxmra, 55 - 82) View more	Positive	01 Jan 2025
NCT04489771 (LITESPARK-013, Pubmed \| Ann Oncol)	Phase 2	Renal Cell Carcinoma VHL disease \| anti-PD-(L)1 regimen	154	Belzutifan 120 mg	pxbsmckacc(hyzqksfeby) = juxfhluswm kyqpjfsdcn (onehavxqkd, -0.5% [-14.0 - 12.9]) View more	Positive	01 Dec 2024
				Belzutifan 200 mg	pxbsmckacc(hyzqksfeby) = gewgpskjeu kyqpjfsdcn (onehavxqkd ) View more

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