Latest news with #VHL
News18
a day ago
- Health
- News18
Why Regular Kidney Cancer Screening After 40 Is a Must
Last Updated: In a world where preventive health is gaining increasing importance, incorporating regular kidney check-ups alongside heart and liver assessments can offer holistic protection Kidney cancer, often dubbed the 'silent killer" of the urogenital tract, is steadily becoming a significant concern among individuals over the age of 40. With a high mortality rate and subtle early symptoms, this disease often goes undetected until it has progressed to an advanced stage. Experts now emphasize that regular screening post-40 can be a lifesaving intervention—especially for high-risk groups. A Growing Concern After 40 According to Dr Kavitha Vijayakumar, AVP & Lab Operations, Metropolis Healthcare Ltd (Tamil Nadu, Andhra Pradesh & Telangana), 'Kidney cancer most commonly occurs after 40 years of age, with a higher frequency in men compared to women. The risk is compounded by lifestyle factors like smoking, alcohol consumption, and hypertension." What makes kidney cancer particularly dangerous is its ability to remain asymptomatic. 'Sixty percent of patients with kidney cancer are indeed asymptomatic, which explains why early diagnosis is so rare. A quarter of them are already in the metastatic stage when diagnosed," she adds. Symptoms, when they do occur, are often vague such as easy fatigue or low back pain which can be easily misattributed to other common conditions. Why Screening Is Crucial 'While cardiac screenings and cholesterol checks have become commonplace after 40, kidney cancer screening is often overlooked despite its severity," notes Dr. Kavitha. She recommends a simple ultrasound, which can be highly sensitive in detecting kidney tumors, especially depending on the size and location of the lesion. These non-invasive screenings can help flag abnormalities before symptoms set in, offering a critical window for early intervention. Dr. Samir Khanna, Director, Urology, CK Birla Hospital, Delhi, echoes these concerns and provides a broader view of the evolving landscape. 'Kidney cancer is most frequently diagnosed between the ages of 50 and 70, but there's a noticeable rise in incidence starting as early as 40. Age is a well-established risk factor—along with smoking, hypertension, obesity, and prolonged exposure to toxins," he explains. Certain populations, especially long-term dialysis patients and those with a family history of kidney cancer or genetic disorders like Von Hippel-Lindau (VHL) syndrome, are particularly vulnerable. 'Fortunately," Dr. Khanna adds, 'screening doesn't need to be complicated. Non-invasive tools like routine urine tests and ultrasounds can help detect tumors incidentally in their early stages—often when the cancer is still manageable through minimally invasive treatments like partial nephrectomy or ablation." Advanced Tools & Technologies In recent years, there's been a significant shift toward innovative screening methods. 'Emerging technologies like liquid biopsies and circulating tumor DNA tests are showing promise in detecting tumors at a molecular level," says Dr. Khanna. 'Artificial intelligence is also being integrated into imaging to better differentiate between benign and malignant kidney masses." These advancements could soon revolutionize early detection, making screening even more precise and accessible. Both experts stress that kidney cancer screening after 40 should not be a luxury—it's a preventive essential, particularly for those with risk factors. As Dr. Kavitha rightly points out, 'Detecting kidney cancer early can mean the difference between a simple outpatient treatment and complex, life-altering surgery." In a world where preventive health is gaining increasing importance, incorporating regular kidney check-ups alongside heart and liver assessments can offer holistic protection. If you're over 40, especially with a personal or family history of the disease, speak to your healthcare provider about getting screened.
Yahoo
18-02-2025
- Health
- Yahoo
WELIREG® (belzutifan) Receives First European Commission Approval for Two Indications
WELIREG is the first and only oral hypoxia-inducible factor-2 alpha inhibitor approved in the European Union RAHWAY, N.J., February 18, 2025--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced that the European Commission (EC) has conditionally approved WELIREG® (belzutifan), Merck's oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, as monotherapy for: The treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated, localized renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), and for whom localized procedures are unsuitable; The treatment of adult patients with advanced clear cell RCC that progressed following two or more lines of therapy that included a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and at least two vascular endothelial growth factor (VEGF) targeted therapies. The EC approval of these two indications is based on results from the LITESPARK-004 and LITESPARK-005 trials, respectively, and follows the positive recommendation from the Committee for Medicinal Products for Human Use adopted in December 2024. This marks the first approval for WELIREG in the European Union (EU). WELIREG is now approved in over 30 countries for certain adult patients with previously treated advanced RCC and in more than 40 countries for adult patients with certain eligible VHL disease-associated tumors. "The approval of WELIREG in the EU introduces the first and only systemic treatment option for adult patients with certain VHL disease-associated tumors for whom localized procedures are unsuitable, and offers a new option for adult patients with advanced clear cell renal cell carcinoma that progressed following a PD-1 or PD-L1 inhibitor and at least two VEGF targeted therapies," said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. "This is an important moment, and we are pleased that WELIREG, a first-in-class HIF-2α inhibitor, can now potentially help these patients in need." This approval allows marketing of WELIREG for these indications in all 27 EU member states, as well as Iceland, Liechtenstein and Norway. The conditional approval of WELIREG will be valid for one year, subject to yearly renewal, pending additional clinical data from LITESPARK-004 and another ongoing Phase 2 trial of WELIREG in patients with certain VHL disease-associated tumors. Timing for commercial availability of WELIREG in individual EU countries will depend on multiple factors, including the completion of national reimbursement procedures. Results in Patients With Certain Eligible VHL Disease-associated Tumors (LITESPARK-004) WELIREG is now the first and only systemic therapy for the treatment of VHL disease-associated tumors in the EU. The approval in adult patients with certain eligible VHL disease-associated tumors is based on objective response rate (ORR) and duration of response (DOR) results from the LITESPARK-004 trial. WELIREG was approved in the U.S. in August 2021 for the treatment of adult patients with VHL disease who require therapy for associated RCC, CNS hemangioblastomas or pNET not requiring immediate surgery based on the results from LITESPARK-004. In patients with VHL disease-associated RCC (n=61), WELIREG showed an ORR of 49% (95% CI, 36-62) (n=30/61); all responses were partial responses (PR). Median DOR for these patients was not reached, with ongoing responses ranging from 2.8+ to 22+ months; among responders, 56% (n=17/30) maintained a response for at least 12 months. Among these 61 patients, the study also evaluated response rates in other common disease-associated tumors including CNS hemangioblastomas and pNET. In patients with VHL disease-associated CNS hemangioblastomas (n=24) in this trial, WELIREG showed an ORR of 63% (95% CI, 41-81) (n=15/24), with a complete response (CR) rate of 4% (n=1/24) and a PR rate of 58% (n=14/24). Median DOR for these patients was not reached, with ongoing responses ranging from 3.7+ to 22+ months; among responders, 73% (n=11/15) maintained a response for at least 12 months. In patients with VHL disease-associated pNET (n=12) in this trial, WELIREG showed an ORR of 83% (95% CI, 52-98) (n=10/12), with a CR rate of 17% (n=2/12) and a PR rate of 67% (n=8/12). Median DOR for these patients was not reached, with ongoing responses ranging from 11+ to 19+ months; among responders, 50% (n=5/10) maintained a response for at least 12 months. Results in Certain Patients With Previously Treated Advanced RCC (LITESPARK-005) The approval in adult patients with advanced clear cell RCC that progressed following two or more lines of therapy, including a PD-1 or PD-L1 inhibitor and at least two VEGF targeted therapies, is based on progression-free survival (PFS) and ORR results from the LITESPARK-005 trial, which was the first trial in advanced RCC to specifically evaluate patients who progressed following these treatments. WELIREG was approved in the U.S. in December 2023 for the treatment of adult patients with advanced RCC following both a PD-1 or PD-L1 inhibitor and a VEGF-tyrosine kinase inhibitor based on the results from LITESPARK-005. In the trial, WELIREG reduced the risk of disease progression or death by 25% (HR=0.75 [95% CI, 0.63-0.90]; p=0.0008) versus everolimus. Median PFS was 5.6 months (95% CI, 3.9-7.0) for WELIREG versus 5.6 months (95% CI, 4.8-5.8) for everolimus. The ORR for WELIREG was 22% (n=82) (95% CI, 18-27), with a CR rate of 3% (n=10) and a PR rate of 19% (n=72), and the ORR for everolimus was 4% (n=13) (95% CI, 2-6), with no patients achieving a CR and a PR rate of 4% (n=13). About LITESPARK-004 LITESPARK-004 is an open-label Phase 2 trial ( NCT03401788) evaluating WELIREG for the treatment of patients with VHL disease who had at least one measurable solid tumor localized to the kidney and who did not require immediate surgery. The study enrolled 61 patients who received WELIREG (120 mg orally once daily) until disease progression or unacceptable toxicity. The primary endpoint is ORR in VHL disease-associated RCC. Secondary endpoints include, DOR, time to response, PFS, time to surgery and safety. Additionally, this study evaluated response rates in other common VHL disease-associated tumors including pNET and CNS hemangioblastomas. About LITESPARK-005 LITESPARK-005 is an open-label, randomized, active-controlled Phase 3 trial ( NCT04195750) evaluating WELIREG compared to everolimus for the treatment of patients with unresectable, locally advanced or metastatic clear cell RCC that progressed following PD-1 or PD-L1 checkpoint inhibitor and VEGF receptor targeted therapies either in sequence or in combination. The trial enrolled 746 patients who were randomized to receive WELIREG (120 mg orally once daily) or everolimus (10 mg orally once daily). The dual primary endpoints are PFS and overall survival. Secondary endpoints include ORR, DOR and safety. About von Hippel-Lindau disease Von Hippel-Lindau disease is a rare genetic disease, which impacts an estimated 200,000 people worldwide and an estimated 10,000 to 15,000 people in Europe. Patients with VHL disease are at risk for recurrent, benign blood vessel tumors as well as some cancerous ones. One of the most commonly occurring tumors is RCC, a form of kidney cancer, which occurs in about 70% of patients with VHL disease. About renal cell carcinoma Renal cell carcinoma is by far the most common type of kidney cancer. Clear cell RCC is considered the most common form of RCC, representing about 70% of all cases. In 2020, more than 130,000 new cases of RCC were diagnosed in Europe. Renal cell carcinoma is about twice as common in men than in women. Approximately 30% of patients with kidney cancer are diagnosed at an advanced stage. About WELIREG® (belzutifan) 40 mg tablets, for oral use Indications in the U.S. Certain von Hippel-Lindau (VHL) disease-associated tumors WELIREG (belzutifan) is indicated for the treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery. Advanced Renal Cell Carcinoma (RCC) WELIREG is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) following a programmed death receptor-1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI). Selected Safety Information for WELIREG 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 as WELIREG can render some hormonal contraceptives ineffective. Anemia WELIREG can cause severe anemia that can require blood transfusion. Monitor for anemia before initiation of, and periodically throughout, treatment. Transfuse patients as clinically indicated. For patients with hemoglobin <8 g/dL, withhold WELIREG until ≥8 g/dL, then resume at the same or reduced dose or permanently discontinue WELIREG, depending on the severity of anemia. For life-threatening anemia or when urgent intervention is indicated, withhold WELIREG until hemoglobin ≥8 g/dL, then resume at a reduced dose or permanently discontinue WELIREG. In LITESPARK-004 (N=61), decreased hemoglobin occurred in 93% of patients with VHL disease and 7% had Grade 3 events. Median time to onset of anemia was 31 days (range: 1 day to 8.4 months). The safety of erythropoiesis-stimulating agents (ESAs) for treatment of anemia in patients with VHL disease treated with WELIREG has not been established. In LITESPARK-005 (n=372), decreased hemoglobin occurred in 88% of patients with advanced RCC and 29% had Grade 3 events. Median time to onset of anemia was 29 days (range: 1 day to 16.6 months). Of the patients with anemia, 22% received transfusions only, 20% received ESAs only, and 12% received both transfusion and ESAs. Hypoxia WELIREG can cause severe hypoxia that may require discontinuation, supplemental oxygen, or hospitalization. Monitor oxygen saturation before initiation of, and periodically throughout, treatment. For decreased oxygen saturation with exercise (e.g., pulse oximeter <88% or PaO2 ≤55 mm Hg), consider withholding WELIREG until pulse oximetry with exercise is greater than 88%, then resume at the same or a reduced dose. For decreased oxygen saturation at rest (e.g., pulse oximeter <88% or PaO2 ≤55 mm Hg) or when urgent intervention is indicated, withhold WELIREG until resolved and resume at a reduced dose or discontinue. For life-threatening or recurrent symptomatic hypoxia, permanently discontinue WELIREG. Advise patients to report signs and symptoms of hypoxia immediately to a healthcare provider. In LITESPARK-004, hypoxia occurred in 1.6% of patients. In LITESPARK-005, hypoxia occurred in 15% of patients and 10% had Grade 3 events. Of the patients with hypoxia, 69% were treated with oxygen therapy. Median time to onset of hypoxia was 30.5 days (range: 1 day to 21.1 months). Embryo-Fetal Toxicity Based on findings in animals, WELIREG can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with WELIREG and for 1 week after the last dose. WELIREG can render some hormonal contraceptives ineffective. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose. Adverse Reactions In LITESPARK-004, serious adverse reactions occurred in 15% of patients, including anemia, hypoxia, anaphylaxis reaction, retinal detachment, and central retinal vein occlusion (1 patient each). WELIREG was permanently discontinued due to adverse reactions in 3.3% of patients for dizziness and opioid overdose (1.6% each). Dosage interruptions due to an adverse reaction occurred in 39% of patients. Those which required dosage interruption in >2% of patients were fatigue, decreased hemoglobin, anemia, nausea, abdominal pain, headache, and influenza-like illness. Dose reductions due to an adverse reaction occurred in 13% of patients. The most frequently reported adverse reaction which required dose reduction was fatigue (7%). The most common adverse reactions (≥25%), including laboratory abnormalities, that occurred in patients who received WELIREG were decreased hemoglobin (93%), fatigue (64%), increased creatinine (64%), headache (39%), dizziness (38%), increased glucose (34%), and nausea (31%). In LITESPARK-005, serious adverse reactions occurred in 38% of patients. The most frequently reported serious adverse reactions were hypoxia (7%), anemia (5%), pneumonia (3.5%), hemorrhage (3%), and pleural effusion (2.2%). Fatal adverse reactions occurred in 3.2% of patients who received WELIREG, including sepsis (0.5%) and hemorrhage (0.5%). WELIREG was permanently discontinued due to adverse reactions in 6% of patients. Adverse reactions which resulted in permanent discontinuation (≥0.5%) were hypoxia (1.1%) and hemorrhage (0.5%). Dosage interruptions due to an adverse reaction occurred in 39% of patients. Of the patients who received WELIREG, 28% were 65 to 74 years, and 10% were 75 years and over. Dose interruptions occurred in 48% of patients ≥65 years of age and in 34% of younger patients. Adverse reactions which required dosage interruption in ≥2% of patients were anemia (8%), hypoxia (5%), COVID-19 (4.3%), fatigue (3.2%), and hemorrhage (2.2%). Dose reductions due to an adverse reaction occurred in 13% of patients. Dose reductions occurred in 18% of patients ≥65 years of age and in 10% of younger patients. The most frequently reported adverse reactions which required dose reduction (≥1.0%) were hypoxia (5%) and anemia (3.2%). The most common (≥25%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (88%), fatigue (43%), musculoskeletal pain (33%), increased creatinine (34%), decreased lymphocytes (34%), increased alanine aminotransferase (32%), decreased sodium (31%), increased potassium (29%), and increased aspartate aminotransferase (27%). Drug Interactions Coadministration of WELIREG with inhibitors of UGT2B17 or CYP2C19 increases plasma exposure of belzutifan, which may increase the incidence and severity of adverse reactions. Monitor for anemia and hypoxia and reduce the dosage of WELIREG as recommended. Coadministration of WELIREG with CYP3A4 substrates decreases concentrations of CYP3A4 substrates, which may reduce the efficacy of these substrates or lead to therapeutic failures. Avoid coadministration with sensitive CYP3A4 substrates. If coadministration cannot be avoided, increase the sensitive CYP3A4 substrate dosage in accordance with its Prescribing Information. Coadministration of WELIREG with hormonal contraceptives may lead to contraceptive failure or an increase in breakthrough bleeding. Lactation Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with WELIREG and for 1 week after the last dose. Females and Males of Reproductive Potential WELIREG can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to initiating treatment with WELIREG. Use of WELIREG may reduce the efficacy of hormonal contraceptives. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with WELIREG and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose. Based on findings in animals, WELIREG may impair fertility in males and females of reproductive potential and the reversibility of this effect is unknown. Pediatric Use Safety and effectiveness of WELIREG in pediatric patients under 18 years of age have not been established. Merck's focus on cancer Every day, we follow the science as we work to discover innovations that can help patients, no matter what stage of cancer they have. As a leading oncology company, we are pursuing research where scientific opportunity and medical need converge, underpinned by our diverse pipeline of more than 25 novel mechanisms. With one of the largest clinical development programs across more than 30 tumor types, we strive to advance breakthrough science that will shape the future of oncology. By addressing barriers to clinical trial participation, screening and treatment, we work with urgency to reduce disparities and help ensure patients have access to high-quality cancer care. Our unwavering commitment is what will bring us closer to our goal of bringing life to more patients with cancer. For more information, visit About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit and connect with us X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn. Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA This news release of Merck & Co., Inc., Rahway, N.J., USA (the "company") includes "forward-looking statements" within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company's management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company's ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company's patents and other protections for innovation products; and the exposure to litigation, including patent litigation, and/or regulatory actions. The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company's Annual Report on Form 10-K for the year ended December 31, 2023 and the company's other filings with the Securities and Exchange Commission (SEC) available at the SEC's Internet site ( Please see Prescribing Information, including information for the Boxed Warning about embryo-fetal toxicity, for WELIREG (belzutifan) at and Medication Guide for WELIREG at View source version on Contacts Media Contacts:Julie Cunningham, (617) 519-6264Michael McArdle, (908) 447-9453 Investor Contacts:Peter Dannenbaum, (732) 594-1579Steven Graziano, (732) 594-1583
Yahoo
27-01-2025
- Business
- Yahoo
FDA Grants Priority Review to Merck's Application for WELIREG® (belzutifan) for the Treatment of Patients With Advanced Pheochromocytoma and Paraganglioma (PPGL)
Acceptance based on objective response rate data from the Phase 2 LITESPARK-015 trial evaluating WELIREG in certain patients with advanced PPGL If approved, WELIREG would be the only available therapy in the U.S. for eligible patients with advanced PPGL RAHWAY, N.J., January 27, 2025--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the U.S. Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) seeking approval of WELIREG® (belzutifan), Merck's oral hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, for the treatment of adult and pediatric patients (12 years and older) with advanced, unresectable, or metastatic pheochromocytoma and paraganglioma (PPGL). The sNDA is based on objective response rate (ORR) and duration of response (DOR) data from the Phase 2 LITESPARK-015 trial, which will be presented at an upcoming medical meeting. The FDA has set a Prescription Drug User Fee Act (PDUFA), or target action, date of May 26, 2025. "Pheochromocytoma and paraganglioma are rare tumors that form in and around the adrenal glands, and currently, there are no approved therapies available in the U.S. for patients with this rare disease," said Dr. Marjorie Green, senior vice president and head of oncology, global clinical development, Merck Research Laboratories. "Today's U.S. filing acceptance demonstrates our commitment to advancing novel therapies, such as WELIREG, to help treat patients with certain rare oncologic diseases. We look forward to working with the FDA to potentially provide this critical option to these patients who urgently need new innovative therapies." WELIREG is the first and only HIF-2α inhibitor therapy approved in the U.S. for the treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors (pNETs) not requiring immediate surgery, based on results from the Phase 2 LITESPARK-004 trial. WELIREG is also approved for certain adult patients with VHL disease-associated tumors in China and 16 additional countries around the world. WELIREG is also approved in the U.S. and Canada for the treatment of adult patients with advanced RCC following a PD-1/PD-L1 inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI), based on results from the Phase 3 LITESPARK-005 trial. Merck is investigating WELIREG in rare oncologic diseases, RCC and other tumor types through a broad clinical development program, including in Phase 2 and 3 trials evaluating WELIREG as monotherapy and in combination with other medicines. About LITESPARK-015 LITESPARK-015 is an open-label, single-arm, multi-cohort Phase 2 trial (NCT04924075) evaluating the efficacy and safety of WELIREG monotherapy in patients with advanced PPGL (Cohort A1), pNETs (Cohort A2), VHL disease-associated tumors (Cohort B1), advanced gastrointestinal stromal tumors (Cohort C), or advanced solid tumors with HIF-2α-related genetic alterations (Cohort D). The primary endpoint is ORR per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) as assessed by blinded independent central review (BICR). Secondary endpoints include DOR, time to response, disease control, progression-free survival, overall survival and safety. The trial enrolled an estimated 322 patients who received WELIREG 120 mg orally once daily. About pheochromocytoma and paraganglioma Pheochromocytoma and paraganglioma (PPGL) are rare adrenal tumors that can be caused by certain genetic syndromes or mutations. It is estimated that up to 2,000 new cases of PPGL are diagnosed each year in the U.S., and up to 52,800 new cases are diagnosed each year worldwide. Pheochromocytoma occur in the center of the adrenal gland, whereas paraganglioma occur in nerve tissue in the adrenal glands and near certain blood vessels and nerves. Up to 25% of PPGL cases are metastatic at diagnosis. About WELIREG® (belzutifan) 40 mg tablets, for oral use Indications in the U.S. Certain von Hippel-Lindau (VHL) disease-associated tumors WELIREG (belzutifan) is indicated for the treatment of adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery. Advanced Renal Cell Carcinoma (RCC) WELIREG is indicated for the treatment of adult patients with advanced renal cell carcinoma (RCC) following a programmed death receptor-1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitor and a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF-TKI). Selected Safety Information for WELIREG 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 as WELIREG can render some hormonal contraceptives ineffective. Anemia WELIREG can cause severe anemia that can require blood transfusion. Monitor for anemia before initiation of, and periodically throughout, treatment. Transfuse patients as clinically indicated. For patients with hemoglobin <8 g/dL, withhold WELIREG until ≥8 g/dL, then resume at the same or reduced dose or permanently discontinue WELIREG, depending on the severity of anemia. For life-threatening anemia or when urgent intervention is indicated, withhold WELIREG until hemoglobin ≥8 g/dL, then resume at a reduced dose or permanently discontinue WELIREG. In LITESPARK-004 (N=61), decreased hemoglobin occurred in 93% of patients with VHL disease and 7% had Grade 3 events. Median time to onset of anemia was 31 days (range: 1 day to 8.4 months). The safety of erythropoiesis-stimulating agents (ESAs) for treatment of anemia in patients with VHL disease treated with WELIREG has not been established. In LITESPARK-005 (n=372), decreased hemoglobin occurred in 88% of patients with advanced RCC and 29% had Grade 3 events. Median time to onset of anemia was 29 days (range: 1 day to 16.6 months). Of the patients with anemia, 22% received transfusions only, 20% received ESAs only, and 12% received both transfusion and ESAs. Hypoxia WELIREG can cause severe hypoxia that may require discontinuation, supplemental oxygen, or hospitalization. Monitor oxygen saturation before initiation of, and periodically throughout, treatment. For decreased oxygen saturation with exercise (e.g., pulse oximeter <88% or PaO2 ≤55 mm Hg), consider withholding WELIREG until pulse oximetry with exercise is greater than 88%, then resume at the same or a reduced dose. For decreased oxygen saturation at rest (e.g., pulse oximeter <88% or PaO2 ≤55 mm Hg) or when urgent intervention is indicated, withhold WELIREG until resolved and resume at a reduced dose or discontinue. For life-threatening or recurrent symptomatic hypoxia, permanently discontinue WELIREG. Advise patients to report signs and symptoms of hypoxia immediately to a healthcare provider. In LITESPARK-004, hypoxia occurred in 1.6% of patients. In LITESPARK-005, hypoxia occurred in 15% of patients and 10% had Grade 3 events. Of the patients with hypoxia, 69% were treated with oxygen therapy. Median time to onset of hypoxia was 30.5 days (range: 1 day to 21.1 months). Embryo-Fetal Toxicity Based on findings in animals, WELIREG can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to the fetus. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with WELIREG and for 1 week after the last dose. WELIREG can render some hormonal contraceptives ineffective. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose. Adverse Reactions In LITESPARK-004, serious adverse reactions occurred in 15% of patients, including anemia, hypoxia, anaphylaxis reaction, retinal detachment, and central retinal vein occlusion (1 patient each). WELIREG was permanently discontinued due to adverse reactions in 3.3% of patients for dizziness and opioid overdose (1.6% each). Dosage interruptions due to an adverse reaction occurred in 39% of patients. Those which required dosage interruption in >2% of patients were fatigue, decreased hemoglobin, anemia, nausea, abdominal pain, headache, and influenza-like illness. Dose reductions due to an adverse reaction occurred in 13% of patients. The most frequently reported adverse reaction which required dose reduction was fatigue (7%). The most common adverse reactions (≥25%), including laboratory abnormalities, that occurred in patients who received WELIREG were decreased hemoglobin (93%), fatigue (64%), increased creatinine (64%), headache (39%), dizziness (38%), increased glucose (34%), and nausea (31%). In LITESPARK-005, serious adverse reactions occurred in 38% of patients. The most frequently reported serious adverse reactions were hypoxia (7%), anemia (5%), pneumonia (3.5%), hemorrhage (3%), and pleural effusion (2.2%). Fatal adverse reactions occurred in 3.2% of patients who received WELIREG, including sepsis (0.5%) and hemorrhage (0.5%). WELIREG was permanently discontinued due to adverse reactions in 6% of patients. Adverse reactions which resulted in permanent discontinuation (≥0.5%) were hypoxia (1.1%) and hemorrhage (0.5%). Dosage interruptions due to an adverse reaction occurred in 39% of patients. Of the patients who received WELIREG, 28% were 65 to 74 years, and 10% were 75 years and over. Dose interruptions occurred in 48% of patients ≥65 years of age and in 34% of younger patients. Adverse reactions which required dosage interruption in ≥2% of patients were anemia (8%), hypoxia (5%), COVID-19 (4.3%), fatigue (3.2%), and hemorrhage (2.2%). Dose reductions due to an adverse reaction occurred in 13% of patients. Dose reductions occurred in 18% of patients ≥65 years of age and in 10% of younger patients. The most frequently reported adverse reactions which required dose reduction (≥1.0%) were hypoxia (5%) and anemia (3.2%). The most common (≥25%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (88%), fatigue (43%), musculoskeletal pain (33%), increased creatinine (34%), decreased lymphocytes (34%), increased alanine aminotransferase (32%), decreased sodium (31%), increased potassium (29%), and increased aspartate aminotransferase (27%). Drug Interactions Coadministration of WELIREG with inhibitors of UGT2B17 or CYP2C19 increases plasma exposure of belzutifan, which may increase the incidence and severity of adverse reactions. Monitor for anemia and hypoxia and reduce the dosage of WELIREG as recommended. Coadministration of WELIREG with CYP3A4 substrates decreases concentrations of CYP3A4 substrates, which may reduce the efficacy of these substrates or lead to therapeutic failures. Avoid coadministration with sensitive CYP3A4 substrates. If coadministration cannot be avoided, increase the sensitive CYP3A4 substrate dosage in accordance with its Prescribing Information. Coadministration of WELIREG with hormonal contraceptives may lead to contraceptive failure or an increase in breakthrough bleeding. Lactation Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with WELIREG and for 1 week after the last dose. Females and Males of Reproductive Potential WELIREG can cause fetal harm when administered to a pregnant woman. Verify the pregnancy status of females of reproductive potential prior to initiating treatment with WELIREG. Use of WELIREG may reduce the efficacy of hormonal contraceptives. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with WELIREG and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with WELIREG and for 1 week after the last dose. Based on findings in animals, WELIREG may impair fertility in males and females of reproductive potential and the reversibility of this effect is unknown. Pediatric Use Safety and effectiveness of WELIREG in pediatric patients under 18 years of age have not been established. Merck's focus on cancer Every day, we follow the science as we work to discover innovations that can help patients, no matter what stage of cancer they have. As a leading oncology company, we are pursuing research where scientific opportunity and medical need converge, underpinned by our diverse pipeline of more than 25 novel mechanisms. With one of the largest clinical development programs across more than 30 tumor types, we strive to advance breakthrough science that will shape the future of oncology. By addressing barriers to clinical trial participation, screening and treatment, we work with urgency to reduce disparities and help ensure patients have access to high-quality cancer care. Our unwavering commitment is what will bring us closer to our goal of bringing life to more patients with cancer. For more information, visit About Merck At Merck, known as MSD outside of the United States and Canada, we are unified around our purpose: We use the power of leading-edge science to save and improve lives around the world. For more than 130 years, we have brought hope to humanity through the development of important medicines and vaccines. We aspire to be the premier research-intensive biopharmaceutical company in the world – and today, we are at the forefront of research to deliver innovative health solutions that advance the prevention and treatment of diseases in people and animals. We foster a diverse and inclusive global workforce and operate responsibly every day to enable a safe, sustainable and healthy future for all people and communities. For more information, visit and connect with us X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn. Forward-Looking Statement of Merck & Co., Inc., Rahway, N.J., USA This news release of Merck & Co., Inc., Rahway, N.J., USA (the "company") includes "forward-looking statements" within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company's management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline candidates that the candidates will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements. Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company's ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company's patents and other protections for innovation products; and the exposure to litigation, including patent litigation, and/or regulatory actions. The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company's Annual Report on Form 10-K for the year ended December 31, 2023 and the company's other filings with the Securities and Exchange Commission (SEC) available at the SEC's Internet site ( Please see Prescribing Information, including information for the Boxed Warning about embryo-fetal toxicity, for WELIREG (belzutifan) at and Medication Guide for WELIREG at View source version on Contacts Media Contacts:Julie Cunningham(617) 519-6264Michael McArdle(908) 447-9453Investor Contacts:Peter Dannenbaum(732) 594-1579Steven Graziano(732) 594-1583
