FDA Grants Priority Review to New Drug Application for the RET Kinase Inhibitor Selpercatinib

On January 29, 2020, Eli Lilly announced that the FDA granted priority review to their New Drug Application for selpercatinib (LOXO-292) for the treatment of patients with advanced RET fusion-positive non–small-cell lung cancer, RET-mutant medullary thyroid cancer, and RET fusion-positive thyroid cancer. The FDA is aiming to provide its decision on the approval of selpercatinib in the third quarter of 2020.

Previously, the FDA granted breakthrough therapy and orphan drug designations for selpercatinib to treat certain patients with advanced RET fusion-positive thyroid cancer and those with RET-altered NSCLC or MTC. The agent was also granted orphan drug designation by the FDA for the treatment of patients with RET fusion-positive NSCLC, RET-mutant MTC, and RET fusion-positive thyroid cancer.

“We are pleased the FDA granted priority review status for the NDA for selpercatinib. This represents an important step toward providing a new precision therapy for people living with certain RET-driven cancers,” stated Anne E. White, President, Lilly Oncology, in a company press release.

Key Takeaways:

• The NDA includes data from the phase 1/2 LIBRETTO-001 clinical trial, the largest study of patients with RET-driven lung and thyroid cancers treated with an RET inhibitor. Data from phase 2 of the study showed an overall response rate (ORR) of 77% in evaluable patients with RET fusion-positive cancers. In 2019, updated data showed an ORR of 68% in patients with lung cancer and an ORR of 56% in patients with thyroid cancer.
• RET fusions have been identified in approximately 2% of NSCLC, 10% to 20% of papillary and other thyroid cancers, and a subset of other cancers. Activating RET point mutations account for approximately 60% of MTC. RET fusion cancers and RET-mutant MTC depend on this single activated kinase for their uncontrolled growth.
• In December 2019, Lilly Oncology opened 2 phase 3 trials: LIBRETTO-431, which will evaluate selpercatinib in treatment-naïve patients with RET fusion-positive NSCLC, and LIBRETTO-531, which will evaluate selpercatinib in treatment-naïve patients with RET-mutant MTC. Each trial will enroll 400 patients.