FDA approves belzutifan for pheochromocytoma or paraganglioma
Regulatory approval: On May 14, 2025, the FDA approved belzutifan (Welireg; Merck) for adult and pediatric patients aged ≥12 years with locally advanced, unresectable, or metastatic pheochromocytoma or paraganglioma (PPGL). Efficacy was supported by the open-label LITESPARK-015 trial (cohort A1; n=72), with an objective response rate of 26% (95% CI, 17–38) by blinded independent central review and median duration of response of 20.4 months (95% CI, 8.3–NR).
FDA approval: belzutifan for PPGL (May 14, 2025)
Type: Regulatory approval
On May 14, 2025, the FDA approved belzutifan (Welireg; Merck & Co., Inc.) for adult and pediatric patients aged 12 years and older with locally advanced, unresectable, or metastatic pheochromocytoma or paraganglioma (PPGL). The agency noted this as the first FDA approval of an oral therapy for PPGL.
Key evidence
Approval was based on LITESPARK-015 (NCT04924075), an open-label, multi-cohort trial. Cohort A1 enrolled 72 patients with measurable disease verified by blinded independent central review (BICR) per RECIST v1.1, histopathologically documented PPGL, and locally advanced or metastatic disease not amenable to surgery or curative treatment.
Primary endpoint: ORR by BICR (RECIST v1.1)
- ORR: 26% (95% CI, 17–38)
- Median DOR: 20.4 months (95% CI, 8.3–NR)
Among 60 patients on baseline antihypertensive medications, 19 (32%; 95% CI, 20–45) had a ≥50% reduction in at least one antihypertensive medication maintained for ≥6 months.
Safety and dosing (label highlights)
Most common adverse reactions (≥25%), including lab abnormalities, included anemia, fatigue, musculoskeletal pain, and others.
Recommended dosing: Adults 120 mg orally once daily; pediatric (≥12 years) weight-based (≥40 kg: 120 mg daily; <40 kg: 80 mg daily), continued until progression or unacceptable toxicity.