Recently, the U.S. Food and Drug Administration (FDA) granted Priority Review to the HIF-2α inhibitor belzutifan for the treatment of patients with von Hippel-Lindau (VHL) disease–associated renal cell carcinoma. The agency also granted Fast Track designation to poziotinib for the treatment of non–small cell lung cancer (NSCLC) in previously treated patients with HER2 exon 20 mutations.
Priority Review for HIF-2α Inhibitor Belzutifan in VHL Disease–Associated Renal Cell Carcinoma
The FDA accepted and granted Priority Review to a new drug application for the hypoxia-inducible factor-2 alpha (HIF-2α) inhibitor belzutifan for the treatment of patients with VHL disease–associated renal cell carcinoma (RCC) not requiring immediate surgery. The FDA has set a Prescription Drug User Fee Act, or target action, date of September 15, 2021.
Belzutifan (also known as MK-6482) is a novel, potent, and selective inhibitor of HIF-2α. Proteins known as hypoxia-inducible factors, including HIF-2α, can accumulate in patients when VHL, a tumor-suppressor protein, is inactivated. If not properly regulated, the accumulation of HIF-2α can stimulate several oncogenes associated with cellular proliferation, angiogenesis, and tumor growth, leading to the growth of both benign and malignant tumors. This inactivation of VHL has been observed in more than 90% of clear cell RCC tumors. Research into VHL biology that led to the discovery of HIF-2α was awarded the Nobel Prize in Physiology or Medicine in 2019.
This application is based on data from Study-004 (ClinicalTrials.gov identifier NCT03401788), a phase II, open-label trial evaluating belzutifan for the potential treatment of patients with VHL disease who had at least one measurable solid tumor localized to the kidney and who did not require immediate surgery. The study enrolled 61 patients who received belzutifan at 120 mg orally once daily until disease progression or unacceptable toxicity. The primary endpoint was objective response rate in VHL disease–associated RCC. Secondary endpoints in RCC tumors include disease control rate, duration of response, time to response, progression-free survival, time to surgery, and safety.
Belzutifan showed a confirmed overall response rate of 36.1% (n = 22/61, 95% confidence interval = 24.2%–49.4%) in patients with VHL disease–associated RCC.
FDA Grants Fast Track Designation to Poziotinib for HER2 Exon 20–Mutated NSCLC
The FDA granted Fast Track designation to poziotinib for the treatment of NSCLC in previously treated patients with HER2 exon 20 mutations.
Poziotinib is a novel, oral epidermal growth factor receptor tyrosine kinase inhibitor that inhibits the tyrosine kinase activity of EGFR (HER1), as well as HER2 and HER4.
There are currently no approved therapies to treat patients with NSCLC and HER2 exon 20 mutations.
“…We presented at the European Society for Medical Oncology Targeted Anticancer Therapies (ESMO TAT) Virtual Congress 2021 (Abstract 36M0) that twice-daily dosing (BID) [of poziotinib] suggests improved antitumor activity and reduced toxicity relative to once-daily dosing. We are optimistic about this BID strategy and we will provide a data update at [the AACR Annual Meeting 2021] in April,” stated Francois Lebel, MD, Chief Medical Officer of Spectrum Pharmaceuticals.
