Welireg (belzutifan)

Consistent with these observations, two different allosteric HIF2 inhibitors, belzutifan and NKT2152, rapidly ameliorated hypercalcemia and cachexia in patients with ccRCC, including in some who did not exhibit objective tumor shrinkage. Our findings support prospective clinical studies to determine whether HIF2 inhibitors can be leveraged not only for tumor control, but also for the treatment of cancer-associated cachexia in renal cell carcinoma.

Radiopharmaceuticals such as 131I-MIBG and 177Lu-DOTATATE continue to play a pivotal role, achieving disease control in many patients. Cytotoxic regimens, particularly temozolomide, remain relevant, with some studies suggesting that SDHB-mutated PPGLs demonstrate a heightened sensitivity associated with MGMT promoter hypermethylation and reduced MGMT expression. Targeted agents are increasingly important: multi-kinase inhibitors such as sunitinib, anlotinib, and cabozantinib have shown meaningful activity. The landmark approval of belzutifan, a HIF-2α inhibitor, in 2025 represents the first oral targeted therapy for advanced/metastatic PPGL, which is particularly relevant for pseudohypoxic Cluster 1 tumors...This review summarizes current evidence and highlights ongoing clinical trials, underscoring a paradigm shift toward precision medicine and rational combination strategies. Collectively, these advances bring cautious optimism that metastatic PPGLs may soon become a more manageable chronic disease with improved survival and quality of life.

In treatment, radioligand therapy (PRRT) is used earlier in appropriate receptor-positive disease; cabozantinib improves progression-free survival after prior therapy; and belzutifan offers a biomarker-guided option for malignant pheochromocytoma/paraganglioma...We appraise strengths and limitations of key trials, note issues of access and toxicity, and highlight active areas in development (SSTR antagonists, alpha emitters, and dose-guided PRRT). Our goal is to provide a concise, evidence-based map of the field to support informed clinical judgment and future research priorities.

Relative standard deviations (RSD) were below 2%, indicating precision and reproducibility. Owing to its simplicity and efficiency, the method is suitable for routine quality control in pharmaceutical laboratories.

These findings indicate that the p.E92G ELOC variant is responsible for the VHL manifestations in this family, and that these tumors are being driven by loss of the VCB-Cul2 E3-ubiquitin ligase complex activity.

P3, N=904, Not yet recruiting, Merck Sharp & Dohme LLC

P3, N=249, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Dec 2026 --> Jun 2027 | Trial primary completion date: Dec 2026 --> Jun 2027

Belzutifan represents a promising treatment option for VHL disease, particularly in patients for whom surgery carries significant risks. The therapy demonstrated effective tumor control and delayed disease progression in most cases. However, anemia remains a key side effect requiring close monitoring and management. Larger, long-term studies are needed to further assess the efficacy and safety of belzutifan in VHL patients and to refine treatment strategies.

P1/2, N=140, Recruiting, Merck Sharp & Dohme LLC | N=100 --> 140

Belzutifan showed antitumor activity with durable responses in participants with advanced pheochromocytoma or paraganglioma. (Funded by Merck Sharp and Dohme, a subsidiary of Merck [Rahway, NJ]; LITESPARK-015 ClinicalTrials.gov number, NCT04924075.).

In hereditary syndromes, progress includes improved characterization of BAP1-TPDS-associated RCC and the expanding role of belzutifan in von Hippel-Lindau disease. Beyond twelve months after pembrolizumab, standard first-line PD-1-based combinations remain the recommended approach. Finally, for localized or oligometastatic recurrences, local treatments should be considered within a multidisciplinary tumour board.

P1, N=14, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed