FDA Grants Priority Review to Belzutifan in Advanced Previously Treated RCC

The FDA has set a Prescription Drug User Fee Act date of January 17, 2024 for belzutifan in advanced renal cell carcinoma.

The FDA has granted priority review to a supplemental new drug application (sNDA) for belzutifan (Welireg) as a treatment for patients with advanced renal cell carcinoma (RCC) previously treated with immune checkpoints and anti-angiogenic agents, according to a press release from Merck.¹

The regulatory agency has set a Prescription Drug User Fee Act date of January 17, 2024 for belzutifan in this indication.

Supporting data for the sNDA came from the phase 3 LITESPARK-005 trial (NCT04195750), in which investigators compared the efficacy of belzutifan with everolimus (Afinitor) in patients with advanced RCC.

Based on a previous pre-specified interim analysis that an independent data monitoring committee conducted, investigators highlighted that treatment with belzutifan led to a clinically meaningful and statistically significant improvement in progression-free survival (PFS) compared with everolimus.² Additionally, belzutifan produced a statistically significant improvement in objective response rate (ORR), one of the trial’s key secondary end points. Investigators also reported a trend towards improvement in overall survival (OS) with belzutifan, although this did not reach statistical significance at the time of the interim analysis.

Belzutifan’s safety profile in the LITESPARK-005 trial appeared to be comparable with previous reports of the agent.

“Patients with advanced RCC whose cancer progresses following immune checkpoint and anti-angiogenic therapies [have] a poorer prognosis, and for those patients, there is a crucial unmet need for new options with an alternative mechanism of action,” Marjorie Green, MD, senior vice president and head of late-state oncology, global clinical development at Merck Research Laboratories, said in the press release.¹ “The FDA’s priority review designation of this application reinforces the urgency to provide new options to previously treated patients with advanced RCC, and we are committed to working closely with the FDA to bring [belzutifan] to these patients as quickly as possible.”

In the open-label randomized phase 3 LITESPARK-005 trial, 746 patients were randomly assigned to receive belzutifan at a 120 mg oral dose once a day or 10 mg of everolimus orally once a day.

The study’s primary end points were PFS per RECIST v1.1 criteria as assessed by blinded independent central review and OS. Secondary end points included ORR, duration of response, adverse effects, and health-related quality of life.

Patients 18 years and older with unresectable, locally advanced or metastatic clear cell RCC and disease progression following treatment with a PD-L1 checkpoint inhibitor plus a VEGF tyrosine kinase inhibitor were able to enroll on the study. Additional eligibility criteria included having no more than 3 prior lines of systemic treatment, documented informed consent, and adequate organ function.

Patients with a known additional malignancy that has required active treatment within 3 years prior to study entry or known central nervous system metastases were not able to enroll on the study. Having clinically significant cardiac disease, moderate to severe hepatic impairment, prior radiotherapy within 2 weeks prior to randomization, major surgery within 3 weeks prior to randomization, or an active infection requiring systemic therapy was also grounds for exclusion.

References

1. FDA accepts for priority review Merck’s supplemental new drug application for WELIREG® (belzutifan) in certain previously treated patients with advanced renal cell carcinoma (RCC). News release. Merck. September 19, 2023. Accessed September 19, 2023. https://shorturl.at/bmnNY
2. Merck announces WELIREG® (belzutifan) phase 3 LITESPARK-005 trial met primary endpoint of progression-free survival in certain previously treated patients with advanced renal cell carcinoma. News release. Merck. August 18, 2023. Accessed September 19, 2023. https://bit.ly/3KNgb0Z