New Drug Application for the RET Kinase Inhibitor Selpercatinib Receives Priority Review

Previously, the FDA had 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 non–small-cell lung cancer (NSCLC) or medullary thyroid cancer (MTC). The agency also granted orphan drug designation 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 Insights:

• The New Drug Application (NDA) for selpercatinib 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.
• Approximately 2% of patients with NSCLC, 10% to 20% of patients with papillary and other thyroid cancers, and patients with a subset of other cancers have RET fusions. 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.