Welireg

Von Hippel-Lindau (VHL) disease-associated renal cell carcinoma (RCC), central nervous system hemangioblastomas, or pancreatic neuroendocrine tumors (pNET) not requiring immediate surgery; Advanced renal cell carcinoma (with cabozantinib and nivolumab, after prior anti-PD-1/PD-L1 therapy)

VHL-associated tumors: 120 mg orally once daily until disease progression or unacceptable toxicity
Advanced RCC: 120 mg orally once daily (with cabozantinib 40 mg daily and nivolumab 480 mg IV q4w)
Take with or without food
Dose reduction: 80 mg once daily, then 40 mg once daily

Tablets: 40 mg

None listed.

• Anemia: Reported in 93% of VHL patients (Grade 3: 7.3%). May require transfusion. Monitor hemoglobin before and during treatment. Withhold for hemoglobin <8 g/dL.
• Hypoxia: Reported in 1.3% of patients. Monitor pulse oximetry. Discontinue for life-threatening hypoxia.
• Embryo-Fetal Toxicity: Can cause fetal harm based on mechanism of action and animal data.

Anemia (93%), fatigue (51%), musculoskeletal pain (30%), dizziness (20%), headache (17%), nausea (16%), decreased visual acuity (13%)

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

Consult the complete prescribing information for drug interactions, including effects on CYP enzymes, transporters, and concomitant medications that may require dose adjustments or monitoring.

Consult the full prescribing information for pregnancy-related considerations.

Refer to prescribing information for lactation guidance.

Pediatric safety and efficacy information is detailed in the full label.

Dose modifications for organ impairment are specified in the complete prescribing information.

Belzutifan is an inhibitor of hypoxia-inducible factor 2 alpha (HIF-2α). In VHL disease, inactivation of the VHL tumor suppressor gene leads to accumulation of HIF-2α and subsequent transcription of genes promoting tumor growth, angiogenesis, and erythropoiesis. Belzutifan blocks the interaction between HIF-2α and HIF-1β (ARNT), thereby reducing transcription of HIF-2α target genes including VEGFA, CCND1, and EPO.

Tmax: 1.5 hours. Half-life: approximately 14 hours. Protein binding: 97%. Metabolized by CYP2C19 and UGT2B17. Excreted in urine (47%) and feces (41%).

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

• Study 004 — Belzutifan in VHL disease-associated RCC. Phase II, n=61.
  🔬 NCT03401788 ↗ 📄 Primary Publication ↗

Welireg has FDA-approved indications across the following cancer types covered on PipelineEvidence: