Welireg Shows Durable Antitumor Activity in People with Advanced Pheochromocytoma and Paraganglioma

Treatment with Welireg (belzutifan; Merck & Co, Rahway, NJ), a hypoxia-inducible factor 2α (HIF-2α) inhibitor, produced durable tumor responses and meaningful blood pressure improvements in people with advanced or metastatic pheochromocytoma or paraganglioma—rare neuroendocrine tumors often driven by HIF-2α pathway dysregulation. The results of a phase 2 clinical trial (NCT04924075), funded by a Merck (Rahway, NJ) company subsidiary and published in The New England Journal of Medicine, demonstrated the antitumor activity of Welireg treatment.

The single-group LITESPARK-015 trial (NCT04924075) included 72 participants with locally advanced or metastatic disease not suitable for curative surgery. All participants received Welireg 120 mg daily until disease progression, unacceptable toxicity, or withdrawal from the study. The primary end point was blinded independent central review (BICR)–assessed objective response rate.

Key findings from the trial include the following:

• At a median follow-up of 30.2 months, 26% of participants had a confirmed objective response (95% CI, 17% to 38%).
• At the median follow-up, 85% of participants showed disease control as assessed by BICR (95% CI, 74% to 92%).
• The median duration of response was 20.4 months (95% CI, 8.3 to not reached [NR]).
• The median progression-free survival was 22.3 months (95% CI, 13.8 to NR).
• At 24 months, the overall survival was 76%.
• In terms of blood pressure, 32% of participants (n=19) reduced antihypertensive doses by ≥50% for ≥6 months.
• Seventy-one participants (99%) experienced treatment-related adverse events; 22% showed anemia grade 3.
• Treatment-related serious adverse events occurred in 8 participants (11%).

Source: Jimenez C, Andreassen M, Durand A, et al. Belzutifan for Advanced Pheochromocytoma or Paraganglioma. N Engl J Med. Published online October 18, 2025. doi:10.1056/NEJMoa2504964