Belzutifan, a hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, is an antineoplastic agent.1
Belzutifan is used for the treatment of von Hippel-Lindau (VHL) disease in adults who require therapy for associated renal cell carcinoma (RCC), CNS hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery.1 The drug has been designated an orphan drug by FDA for the treatment of this disease.4
Von Hippel-Lindau (VHL) disease is caused by aberrations (mutations or deletions) to the VHL gene encoding the von Hippel-Lindau tumor suppressor protein (pVHL).2 The most common tumors associated with VHL are retinal and CNS hemangioblastomas, pheochromocytoma, endolymphatic sac and pancreatic islet tumors, and RCC of clear cell histology (ccRCC).2 VHL aberrations (mutation, methylation, and/or chromosomal loss) account for the majority of hereditary and sporadic ccRCC cases.2
Efficacy of belzutifan in the treatment of VHL is based principally on the results of 61 patients with VHL-associated RCC (based on the presence of a VHL germline alteration and at least 1 measurable solid tumor localized to the kidney) in an open-label, clinical trial.1, 6 Patients enrolled in the study could also have other VHL-associated tumors including CNS hemangioblastomas or pNET based on the presence of at least one measurable solid tumor in the brain/spine or pancreas, respectively.1 Patients with metastatic disease were excluded.1 In this study, patients received belzutifan 120 mg once daily until disease progression or unacceptable toxicity occurred.1 The primary efficacy outcome for the treatment of VHL-associated RCC was overall response rate as assessed by an independent review committee (IRC).1, 6 Secondary outcomes included duration of response and time to response.1, 6 The median age of patients was 41 years; 53% were male; 90% were white, 3.3% were Black or African-American, 1.6% were Asian, 1.6% were Native Hawaiian or other Pacific Islander, 82% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0, and 84% had VHL type I disease.1 The median diameter of RCC target lesions as determined by a central IRC was 2.2 cm.1 The median time from initial radiographic diagnosis of VHL-associated RCC to initiation of belzutifan therapy was 17.9 months (range 2.8-96.7).1 The majority of patients (77%) had previously undergone surgical procedures for RCC.1
In patients with VHL-associated RCC, the overall response rate was 49%; none of the patients achieved complete response.1 In patients with VHL-associated RCC, the median time to response was 8 months.1 The median duration of response had not been reached at the time of analysis; however, 56% of patients had a duration of response of at least 12 months.1
In the subgroups of patients with VHL-associated CNS hemangioblastomas (24 patients) and pNET (12 patients), the overall response rate was 63 and 83%, respectively; complete response was achieved in 4 and 17% of patients with VHL-associated CNS hemangioblastomas and pNET, respectively.1 In patients with VHL-associated CNS hemangioblastomas and pNET, the median time to response was 3.1 and 8.1 months, respectively.1 The median duration of response had not been reached at the time of analysis; however, 73 and 50% of patients with VHL-associated CNS hemangioblastomas and pNET, respectively, had a duration of response of at least 12 months.1 Decreases in size of CNS hemangioblastoma-associated peritumoral cysts and syringes were observed.1
Belzutifan is also being investigated in combination regimens (e.g., cabozantinib or lenvatinib plus pembrolizumab)† for the treatment of ccRCC† and other solid tumors†.7
Belzutifan is used for the treatment of adults with advanced RCC with a clear cell component following treatment with 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).1
Efficacy of belzutifan in the treatment of advanced RCC is based principally on an open-label, randomized, phase 3 study in 746 patients with unresectable, locally advanced, or metastatic clear cell RCC with evidence of disease progression after 1 to 3 lines of prior systemic therapy, including a PD-1 or PD-L1 inhibitor and a VEGF-TKI.1 Patients were also required to have measurable disease per response evaluation criteria in solid tumors (RECIST v1.1).1
Patients were randomized in a 1:1 ratio to receive belzutifan 120 mg or everolimus 10 mg once daily.1 Randomization was stratified by International Metastatic RCC Database Consortium (IMDC) risk categories (favorable, intermediate, or poor) and number of prior VEGF receptor targeted therapies.1 Patients were evaluated radiologically at week 9 from the date of randomization, then every 8 weeks through week 49, and every 12 weeks thereafter.1 The median age of patients was 63 years (range 22 to 90 years); 78% were male, 79% were white, 12% were Asian, 1% were Black or African American, 11% were Hispanic or Latino, 44% had an ECOG performance status of 0, and 55% had an ECOG performance status of 1.1 In this study, 13% of patients had 1 prior line of therapy, 43% of patients had 2 prior lines of therapy, and 43% had 3 prior lines of therapy; 49% received 2 to 3 prior VEGF receptor targeted therapies.1 Patient distribution by IMDC risk categories was as follows: favorable in 22%, intermediate in 66%, and poor in 12%.1 Common sites of metastasis were the lungs (65%), lymph nodes (59%), and bone (49%).1 The two primary efficacy endpoints of the study were progression free survival (PFS), measured by blinded independent investigator assessment using RECIST v1.1, and overall survival.1 An additional efficacy endpoint included objective response rate (ORR), which was also assessed by independent blinded review using RECIST v1.1.1
PFS was significantly improved with belzutifan compared with everolimus (hazard ratio of 0.75); the median duration of PFS was similar at 5.6 months for both groups.1, 11 ORR was 22% in patients receiving belzutifan compared with 4% in those receiving everolimus; complete response occurred in 3% of patients who received belzutifan compared with no patients who received everolimus.1 More patients remained progression-free with belzutifan versus everolimus at 12 months (PFS rate of 33.7% versus 17.6%) and 18 months (PFS rate of 22.5% versus 9%).11 Overall survival rates were immature at the time of data analysis.12
Pheochromocytoma or Paraganglioma
Belzutifan is used for the treatment of adults and pediatric patients ≥12 years of age with locally advanced, unresectable, or metastatic pheochromocytoma or paraganglioma.1
Efficacy of belzutifan in the treatment of locally advanced, unresectable, or metastatic pheochromocytoma or paraganglioma is based principally on an open-label, multi-cohort clinical trial involving 72 patients.1 Patients were administered belzutifan 120 mg orally once daily until disease progression or unacceptable toxicity.1
The median age of patients was 52 years (range: 22 to 77 years); 58% were male, 93% were White, 4.2% were Black or African American, 1.4% were Asian, 6% were Hispanic or Latino, 54% had an ECOG performance status of 0, and 46% had an ECOG performance status of 1.1 In this study, the median number of prior therapies was 1 (range: 0 to 5).1 The primary efficacy outcome of the study was ORR; additional efficacy outcomes included duration of response, time to response, and the number of patients who had a reduction in ≥1 antihypertensive medication by ≥50% maintained for at least 6 months.1 Results revealed a confirmed ORR of 26% and median duration of response of 20.4 months.1 The median time to response was 11 months.1 Nineteen patients experienced a reduction in ≥1 antihypertensive medication by ≥50% maintained for at least 6 months.1
Belzutifan is administered orally once daily, at the same time each day, without regard to food.1 Belzutifan tablets should be swallowed whole; do not chew, crush or split tablets.1
If a dose of belzutifan is missed, take the prescribed dose as soon as possible on the same day and then resume the regular daily schedule the following day; an additional dose should not be administered to replace the missed dose.1 If vomiting occurs any time after a dose of belzutifan is taken, do not replace the vomited dose; take the next dose at the next scheduled time.1
Belzutifan tablets should be stored at 20-25°C (excursions permitted between 15-30°C).1
For the treatment of von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC), CNS hemangioblastomas, or pancreatic neuroendocrine tumors (pNET) in patients who do not require immediate surgery, the recommended adult dosage of belzutifan is 120 mg orally once daily.1 Therapy with the drug should be continued until disease progression or unacceptable toxicity occurs.1
For the treatment of advanced RCC with a clear cell component following treatment with 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), the recommended adult dosage of belzutifan is 120 mg orally once daily.1 Therapy with the drug should be continued until disease progression or unacceptable toxicity occurs.1
Pheochromocytoma or Paraganglioma
For the treatment of locally advanced, unresectable, or metastatic pheochromocytoma or paraganglioma in adults and pediatric patients ≥12 years of age, the recommended dose is based on body weight.1 For patients weighing <40 kg, the recommended dose is 80 mg orally once daily.1 For patients weighing ≥40 kg, the recommended dose is 120 mg orally once daily.1 Therapy with the drug should be continued until disease progression or unacceptable toxicity occurs.1
If adverse reactions occur during belzutifan therapy, temporary interruption of therapy, dosage reduction, and/or permanent discontinuance of the drug may be necessary.1 If dosage reduction is required, the dosage of belzutifan should be reduced as described in Table 1.1
Dose Reduction Level | Dosage Reduction after Recovery from Toxicity |
|---|---|
(Initial Dosage = 120 mg once daily) | |
First | Resume at 80 mg once daily |
Second | Resume at 40 mg once daily |
Third | Permanently discontinue drug |
If an adverse reaction occurs, modify dosage accordingly (see Table 2).1
Adverse Reaction and Severity | Modification |
|---|---|
Anemia | |
Hemoglobin <8 g/dL or anemia requiring RBC transfusion | Withhold therapy until hemoglobin ≥8 g/dL, and then resume at the same or reduced dosage or discontinue drug depending on severity |
Life-threatening severity or anemia requiring urgent intervention | Withhold therapy until hemoglobin ≥8 g/dL, and then resume at reduced dosage or permanently discontinue drug |
Hypoxia | |
Decreased oxygen saturation with exercise (e.g., pulse oximeter <88%) | Consider withholding therapy until hypoxia resolves, and then resume at same or reduced dosage depending on severity |
Decreased oxygen saturation at rest (e.g., pulse oximeter <88% or PaO2≤55 mm Hg) or hypoxia requiring urgent intervention indicated | Withhold therapy until hypoxia resolves, and then resume at reduced dosage or permanently discontinue drug depending on severity |
Life-threatening or recurrent symptomatic hypoxia | Permanently discontinue drug |
Other Toxicity | |
Grade 3 | Withhold therapy until toxicity improves to grade 2 or less, and then consider resuming at reduced dosage |
If grade 3 toxicity recurs on a reduced dosage, permanently discontinue drug | |
Grade 4 | Permanently discontinue drug |
No dosage modification is recommended in patients with mild (total bilirubin concentration not exceeding the ULN with AST concentration exceeding the ULN or total bilirubin concentration exceeding the ULN, but not more than 1.5 times the ULN, with any AST concentration) or moderate (total bilirubin within range of >1.5 times the ULN and ≤3 times the ULN and any AST or Child-Pugh B) hepatic impairment.1
Not studied in patients with severe hepatic impairment (total bilirubin concentration >1.5 times the ULN with any AST concentration).1
Patients with moderate or severe hepatic impairment should be monitored for increased adverse reactions and dosage modified as recommended.1
No dosage modification is recommended in patients with patients with renal impairment, including end-stage renal disease.1 Patients with severe renal impairment (estimated glomerular filtration rate [eGFR] 15-29 mL/min) should be monitored for increased adverse reactions and dosage modified as recommended.1
The manufacturer makes no specific dosage recommendations for geriatric patients.1
Fetal/Neonatal Morbidity and Mortality
A boxed warning about the risk of embryo-fetal toxicity is included in the prescribing information for belzutifan.1 Belzutifan may cause fetal harm if administered to pregnant women; embryotoxicity and malformations have been demonstrated in animals.1 There are no available data regarding use of belzutifan in pregnant women to inform a drug-associated risk.1 In animal reproduction studies, embryofetal lethality, reduced fetal body weight, and fetal skeletal malformation were observed in pregnant rats receiving belzutifan at exposure levels ≥0.2 times the human exposure at the recommended 120 mg once daily dosage.1 A boxed warning about the risk of embryo-fetal toxicity has been included in the prescribing information for belzutifan.1
Avoid pregnancy during belzutifan therapy.1 Verify pregnancy status prior to initiation of belzutifan therapy in females of reproductive potential.1 Advise females of reproductive potential and males who are partners of such females to use effective nonhormonal contraceptive methods during belzutifan therapy and for 1 week after the last dose.1 Concomitant use of belzutifan with some hormonal contraceptives may result in contraceptive failure.1 Patients should be apprised of the potential hazard to the fetus if belzutifan is used during pregnancy.1
Other Warnings and Precautions
Severe anemia, sometimes requiring blood transfusion, has been reported in patients receiving belzutifan.1 In the principal efficacy study evaluating belzutifan in patients with von Hippel-Lindau (VHL) disease, anemia occurred in 93% of patients and was grade 3 in 7% of patients.1 In the principal efficacy study evaluating belzutifan in patients with advanced renal cell carcinoma (RCC), decreased hemoglobin occurred in 88% of patients and was grade 3 in 29% of patients.1 In the principal efficacy study evaluating belzutifan in patients with pheochromocytoma or paraganglioma, anemia occurred in 96% of patients and was grade 3 in 22% of patients.1 The median time to onset of anemia was 31 days (range: 1 day to 8.4 months) in the study in patients with VHL disease, 29 days (range: 1 day to 16.6 months) in the study in patients with RCC, and 29 days (range: 1 day to 22.1 months) in the study in patients with pheochromocytoma or paraganglioma.1
Reductions in plasma levels of erythropoietin are dose- and exposure-dependent at belzutifan dosages up to 120 mg once daily.1 Maximum erythropoietin suppression (mean percent decrease from baseline of approximately 60%) occurred after 2 consecutive weeks of belzutifan therapy; however, mean erythropoietin levels gradually returned to baseline values after 12 weeks of therapy.1 The incidence of grade 3 anemia increases with higher belzutifan exposure in patients with baseline hemoglobin levels <12 mg/dL.1
Monitor for anemia prior to initiation of belzutifan and periodically during therapy.1 The incidence or severity of anemia may be increased in patients who are dual UGT2B17 and CYP2C19 poor metabolizers; therefore, such patients should be closely monitored for anemia during therapy with belzutifan.1 If anemia occurs, temporary interruption of belzutifan therapy, dosage reduction, or discontinuance of therapy may be necessary; patients should also be transfused as clinically indicated.1
Safety of erythropoiesis-stimulating agents (ESAs) for the treatment of anemia in patients with VHL disease have not been established.1 Randomized controlled trials in cancer patients receiving myelosuppressive chemotherapy and ESAs have shown that ESAs increase the risk of death and serious cardiovascular reaction, and decrease progression-free survival and/or overall survival.1
Severe hypoxia, sometimes requiring discontinuance of therapy, supplemental oxygen, or hospitalization, can occur in patients receiving belzutifan.1 In the principal efficacy studies evaluating belzutifan in patients with VHL disease, advanced RCC, or pheochromocytoma or paraganglioma, hypoxia occurred in 1.6%, 15%, and 13% of patients, respectively.1
Monitor oxygen saturation prior to initiation of belzutifan and periodically during therapy.1 If hypoxia occurs, temporary interruption of belzutifan therapy, dosage reduction, or discontinuance of therapy may be necessary.1
Belzutifan may cause fetal harm if administered to pregnant females based on its mechanism of action and animal findings.1
It is not known whether belzutifan or its metabolites are distributed into human milk or if the drug has any effect on milk production or the breast-fed infant.1 Females should not breast-feed during therapy with belzutifan and for 1 week after the last dose.1
Females and Males of Reproductive Potential
Verify pregnancy status in females of reproductive potential prior to initiation of belzutifan therapy.1 Females of reproductive potential and males who are partners of such females should be advised to use effective nonhormonal contraception during treatment with belzutifan and for 1 week after the last dose.1
Results of animal studies suggest that belzutifan may impair male and female fertility; reversibility of this effect is unknown.1
Safety and efficacy of belzutifan have been established in pediatric patients ≥12 years of age for the treatment of locally advanced, unresectable, or metastatic pheochromocytoma or paraganglioma.1 Clinical data supporting use of belzutifan for this indication in pediatric patients includes an adequate and well-controlled study in adults with additional pharmacokinetic data.1
In the principal efficacy study in patients with VHL disease, 3.3% of patients were 65 years and older.1 Insufficient data to determine whether patients 65 years of age or older respond differently from younger adults.1
In the principal efficacy study in patients with advanced RCC, 28% of patients were 65 to 74 years of age and 10% were 75 years of age and older.1 No overall difference in efficacy was reported between patients who were ≥65 years of age and younger patients.1
In the principal efficacy study in patients with pheochromocytoma or paraganglioma, 13% of patients were 65 years of age and older and 4.2% were 75 years of age and older.1 There were an insufficient number of patients 65 years of age and older to determine whether these patients respond differently from younger patients.1
No clinically significant differences in mean belzutifan exposure were observed between patients with normal hepatic function and those with mild hepatic impairment.1 Belzutifan exposure increased by 1.5-fold in patients with moderate hepatic impairment (Child-Pugh B) compared to patients with normal hepatic function.1 Patients with severe hepatic impairment have not been evaluated.1
No clinically significant differences in mean belzutifan exposure were observed between patients with normal renal function and those with mild (eGFR 60-89 mL/min) or moderate (eGFR 30-59 mL/min) renal impairment and those with end-stage renal disease (eGFR <15 mL/min) requiring dialysis.1
Pharmacogenomic Considerations
Patients who are dual UGT2B17 and CYP2C19 poor metabolizers may have an increased incidence and severity of adverse reactions (e.g., anemia, hypoxia) due to increased systemic exposure to belzutifan.1 Closely monitor patients who are dual UGT2B17 and CYP2C19 poor metabolizers for anemia and hypoxia during therapy with belzutifan.1
The 24-hour AUC of belzutifan at steady state is increased by 2-, 1.6-, or 3.2-fold in patients who are UGT2B17, CYP2C19, or dual UGT2B17 and CYP2C19 poor metabolizers, respectively, compared to those who are UGT2B17 normal (extensive) metabolizers and CYP2C19 non-poor (ultrarapid, rapid, normal, and intermediate) metabolizers.1 UGT2B17 poor metabolizers who are homozygous for the UGT2B17*2 allele have absent UGT2B17 enzyme activity.1 CYP2C19 poor metabolizers (such as *2/*2, *3/*3, *2/*3) have significantly reduced or absent CYP2C19 enzyme activity.1
Approximately 15% of white, 6% of Black or African American, and up to 77% of certain Asian populations are UGT2B17 poor metabolizers.1 Approximately 2% of White, 5% of Black or African American, and up to 19% of certain Asian populations are CYP2C19 poor metabolizers.1 Approximately 0.4% of white, 0.3% of Black or African-American, and up to 15% of certain Asian populations are dual UGT2B17 and CYP2C19 poor metabolizers.1
The most common (≥25%) adverse reactions in patients with VHL disease include decreased hemoglobin, fatigue, increased serum creatinine, headache, dizziness, increased glucose levels, and nausea.1
The most common (≥25%) adverse reactions in patients with advanced RCC include decreased hemoglobin, fatigue, musculoskeletal pain, increased serum creatinine, decreased lymphocytes, increased alanine aminotransferase, decreased sodium, increased potassium, and increased aspartate aminotransferase.1
The most common (≥25%) adverse reactions in patients with pheochromocytoma or paraganglioma include anemia, fatigue, musculoskeletal pain, decreased lymphocytes, increased alanine aminotransferase, increased aspartate aminotransferase, increased calcium, dyspnea, increased potassium, decreased leukocytes, headache, increased alkaline phosphatase, dizziness, and nausea.1
Belzutifan is metabolized primarily by UGT2B17 and CYP2C19, and to a lesser extent by CYP3A4.1
In vitro, belzutifan does not inhibit CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4.1 In vitro studies also indicate that belzutifan does not induce CYP1A2 or 2B6.1
Belzutifan is a substrate of P-gp, OATP1B1, and OATP1B3.1 Belzutifan is not a substrate of BCRP.1 Belzutifan inhibits MATE2K, but does not inhibit P-gp, BCRP, OATP1B1, OATP1B3, OAT1, OAT3, OCT2 or MATE1.1
Drugs Affecting or Affected by Hepatic Microsomal Enzymes
Concomitant use of belzutifan with inhibitors of UGT2B17 or CYP2C19 increases belzutifan exposure, which may increase the risk of adverse effects (e.g., anemia, hypoxia).1
If concomitant use of belzutifan and inhibitors of UGT2B17 or CYP2C19 is necessary, monitor patients for anemia and hypoxia; the dosage of belzutifan should be reduced for adverse effects as clinically indicated.1
Drugs Metabolized by Hepatic Microsomal Enzymes
Concomitant use of belzutifan with CYP3A4 substrates may result in decreased concentrations of the substrate drug and reduced efficacy.1 The pharmacokinetic interaction may be more pronounced in patients who are dual UGT2B17 and CYP2C19 poor metabolizers.1 When belzutifan was coadministered with midazolam (a sensitive CYP3A4 substrate), the AUC and peak plasma concentration of midazolam decreased by 40 and 34%, respectively.1 Midazolam AUC is predicted to decrease up to 70% in patients who are dual UGT2B17 and CYP2C19 poor metabolizers.1
Avoid concomitant use with sensitive CYP3A4 substrates.1 If concomitant use cannot be avoided with sensitive CYP3A4 substrates, the dosage of the substrate drug should be increased according to the manufacturer's labeling for the substrate drug.1
Concomitant use of belzutifan with oral hormonal contraceptives (CYP3A4 substrate) may result in decreased concentrations of the hormonal contraceptive, contraceptive failure, and increased risk of breakthrough bleeding.1, 9 A nonhormonal contraceptive method should be used during belzutifan therapy.1
Belzutifan, a hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor, is an antineoplastic agent.1 In von Hippel-Lindau (VHL) disease, the lack of functional VHL proteins results in an accumulation of HIF-2α, a transcriptional factor that plays a role in oxygen sensing by regulating genes that promote adaptation to hypoxia.1 Under normal oxygen levels, HIF-2α is targeted for ubiquitin-proteasomal degradation by VHL protein.1 Absence of functional VHL protein results in stabilization and accumulation of HIF-2α, which subsequently interacts with HIF-1β to form a transcriptional complex that induces expression of downstream genes (e.g., genes associated with cellular proliferation, angiogenesis, tumor growth).1 Belzutifan binds to HIF-2α and, in conditions of hypoxia or impairment of VHL protein function, blocks formation of the HIF-2α-HIF-1β transcriptional complex, resulting in reduced transcription and expression of HIF-2α target genes.1, 2, 3 In vitro, belzutifan demonstrated anti-tumor activity in mouse xenograft models of renal cell carcinoma.1
The peak plasma concentration and systemic exposure to belzutifan are dose proportional over the oral dose range of 20-120 mg.1 Steady state concentrations are achieved in approximately 3 days.1 Peak plasma concentrations of belzutifan are reached in a median of 1-2 hours following oral administration.1 The exposure of belzutifan in pediatric patients ≥12 years of age is predicted to be within range of that observed in adults at the recommended dosage.1 Administration of belzutifan with a high-fat, high-calorie meal delayed time to peak plasma concentration by approximately 2 hours, but had no clinically significant effect on peak plasma concentration or AUC.1 Belzutifan is 45% plasma protein bound.1 The half-life of belzutifan is 14 hours.1 Belzutifan is metabolized primarily by UGT2B17 and CYP2C19, and to a lesser extent by CYP3A4.1
Age, sex, race, and body weight (range 40-166 kg) do not have clinically important effects on belzutifan exposure.1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Belzutifan can only be obtained through designated specialty pharmacies.10 Contact manufacturer for specific availability information.10
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablet, film-coated | 40 mg | Welireg® | Merck Sharp & Dohme Corp. |
1. Merck Sharp & Dohme Corp. Welireg® (belzutifan) tablets prescribing information. Kenilworth, NJ; 2025 May. [Web]
2. Deeks ED. Belzutifan: First Approval. Drugs . 2021; 81:1921-1927. [PubMed 34613603]
3. Choueiri TK, Bauer TM, Papadopoulos KP et al. Inhibition of hypoxia-inducible factor-2α in renal cell carcinoma with belzutifan: a phase 1 trial and biomarker analysis. Nat Med . 2021; 27:802-805. [PubMed 33888901]
4. Food and Drug Administration. FDA Application: Search orphan drug designations and approvals. Silver Spring, MD. From FDA web site. [Web]
6. Srinivasan R, Donskov F, Iliopoulos O, et al. Phase 2 study of belzutifan (MK-6482), an oral hypoxia-inducible factor 2α (HIF-2α) inhibitor, for Von Hippel-Lindau (VHL) disease-associated clear cell renal cell carcinoma (ccRCC). J Clin Oncol. 2021;39(15_suppl):4555-4555.
7. US National Library of Medicine. Clinicaltrials.gov. [Web]
9. Food and Drug Administration. Center for Drug Evaluation and Research. Application number: 215383Orig1s000: Multi-discipline review. From FDA website. [Web]
10. Merck. Welireg® The Merck Access Program: Specialty pharmacy network. From Merck for US Healthcare Professionals website. [Web]
11. Albiges L, Rini K, Peltola GA, et al. Belzutifan versus everolimus in participants (pts) with previously treated advanced clear cell renal cell carcinoma (ccRCC): Randomized open-label phase III LITESPARK-005 study (Abstract). Annals of Oncology. 2023; 34 (Supp 2):S1329-1330.
12. US Food and Drug Administration. Supplemental approval letter for Welireg (belzutifan). 2023 Dec 14. From the FDA website. [Web]