FDA to Conduct a Quick Review of sNDA for Belzutifan in Advanced RCC

• The FDA has set a Prescription Drug User Fee Act (PDUFA), or target action, date of January 17, 2024, for the supplemental new drug application for belzutifan (Welireg) in adult patients with advanced renal cell carcinoma (RCC).¹

• FDA approval of belzutifan for the treatment of adult patients with RCC who progressed on immune checkpoint and anti-angiogenic agents would provide a new mechanism of action for advanced RCC.

• Full results from the study will be announced at an upcoming medical meeting.²

The FDA has granted priority review to the supplemental new drug application (sNDA) for belzutifan, which is seeking approval of the drug for the treatment of adult patients with advanced RCC following treatment with immune checkpoint and anti-angiogenic agents.¹

Findings from the phase 3 LITESPARK-005 study (NCT04195750) trial uphold the sNDA for belzutifan. Results recently announced that belzutifan achieved a statistically significant and clinical meaningful improvement in progression-free survival (PFS) over everolimus (Afinitor), reaching the primary end point of LITESPARK-005. There was also a statistically significant improvement in the key secondary end point of overall response rate with belzutifan vs everolimus.

“Patients with advanced RCC whose cancer progresses following immune checkpoint and anti-angiogenic therapies face a poorer prognosis, and for those patients, there is a crucial unmet need for new options with an alternative mechanism of action,” said Marjorie Green, MD, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories, in a press release. “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.”

Image Credit: © Nilima - www.stock.adobe.com

The open-label, randomized, phase 3 study enrolled approximately 736 patients with advanced RCC who progressed after treatment with anti-PD-1/PD-L1 and VEGF-targeted therapies. Patients were randomized to receive either belzutifan 120 mg orally once daily or everolimus 10 mg orally once daily. The coprimary end points of the study are PFS and overall survival. Additional secondary end points being evaluated in the study include duration of response, the number of patient who experience 1 or more adverse events (AEs), the number of patients who discontinue study treatment as a result of AEs, time to deterioration (TTD) of health-related quality of life (HRQOL), TTD in physical functioning, TTD in disease symptoms, change from baseline in HRQOL per the EORTC Core Quality of Life questionnaire C30 (EORTC QLQ-C30) items 29 and 30 score, change from baseline in physical functioning based on the EORTC QLQ-C30 items 1- 5 score, change from baseline in disease symptoms according to the functional Assessment of Cancer Therapy Kidney Cancer Symptom Index-Disease Related Symptoms items 1-9 score, and change from baseline in European Quality of Life 5 Dimensions per the 5-level Questionnaire Health Utility score.³

Patients with unresectable, locally advanced, or metastatic disease were eligible to enroll in the study given they had no more than 3 prior systemic agents for locally advanced or metastatic RCC and had adequate organ function. However, the study excluded patients who received any prior systemic anticancer antibody, radiotherapy within 2 weeks before randomization in LITESPARK-005, received a vaccine within 30 days prior to randomization, had major surgery within 3 weeks, are receiving any strong inhibitors of cytochrome P450 3A4 that cannot be discontinued during the study, strong inducers of CYP3A4 that cannot be discontinued for the duration of the study, or investigational agents.

Further, patients with certain comorbidities or infections that may interfere with the efficacy or safety of treatment are excluded from the study.

“If these data lead to the approval of belzutifan for the treatment of refractory RCC, it provides patients and practitioners with an active, well-tolerated treatment option when patients progress on prior lines of therapy. The [AE] profile, with anemia, fatigue and hypoxemia being most common AEs, is easily manageable, making it an attractive choice,” Eric Jonasch, MD, professor in the department of genitourinary medical oncology, division of cancer medicine, at The University of Texas MD Anderson Cancer Center in Houston, TX, previously told Targeted Oncology™.

_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. September 19, 2023. Accessed September 19, 2023. https://tinyurl.com/mbchkwav}

_{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://tinyurl.com/5duv497t}

_{3. A study of belzutifan (MK-6482) versus everolimus in participants with advanced renal cell carcinoma (MK-6482-005). ClinicalTrials.gov. Updated August 1, 2022. Accessed September 19, 2023. https://tinyurl.com/3ejtc595}