January 29, 2020，Eli Lilly recently announced that the US Food and Drug Administration (FDA) has accepted new drug applications (NDA) for selpercatinib (LOXO-292) and granted priority review. That the drug is an oral RET kinase inhibitor used to treat patients with advanced RET fusion-positive non-small cell lung cancer (NSCLC), RET mutant medullary thyroid carcinoma (MTC), and RET fusion-positive thyroid cancer. The FDA has designated the NDA's prescription drug user fee method (PDUFA) target date to be the third quarter of 2020.

Selpercatinib (LOXO-292) is a potent, oral, highly selective transfection rearrangement (RET) kinase inhibitor for the treatment of cancer patients with abnormal RET. The RET gene is a proto-oncogene that undergoes rearrangement during transfection, and hence its name. This gene encodes a cell membrane receptor tyrosine kinase, and its abnormality is a rare driver of many types of tumors.

This NDA is based on data from Phase I / II clinical study LIBRETTO-001. The study is the largest clinical study evaluating one kind RET inhibitor to treat RET altered cancer patients. The results showed that the ORR of selpercatinib in patients with RET-mutated medullary thyroid carcinoma (MTC) who had not previously received treatment (initial treatment) and had previously received treatment (treatment) were 59% and 56%, respectively. Previously published data on the NSCLC cohort showed that the ORR of selpercatinib in newly-treated and treated RET fusion-positive NSCLC patients were 85% and 68%, respectively; in addition, selpercatinib was the first RET that showed strong central nervous system (CNS) activity Inhibitor, CNS ORR is as high as 91%.

It is estimated that RET fusion exists in about 2% of non-small cell lung cancer (NSCLC), 10-20% of papillary thyroid cancer (PTC) and other types of thyroid cancer, and other cancers (such as colorectal cancer) subgroups; RET point mutations are present in approximately 60% of medullary thyroid carcinoma (MTC). RET fusion and RET point mutation cancers mainly rely on the activation of RET kinase to maintain their proliferation and survival. This dependence is often called "oncogene addiction", making these tumors highly sensitive to small molecule inhibitors targeting RET.

Selpercatinib is designed to inhibit natural RET signal transduction and the expected acquired drug resistance mechanism. The drug is currently in clinical development for patients with abnormal RET kinase in tumors.

In the United States, the FDA has granted selpercatinib a breakthrough drug qualification (BTD) for the treatment of three types of patients, specifically: (1) Patients with metastatic RET fusion-positive NSCLC who progressed after receiving platinum-containing chemotherapy and a PD-1 or PD-L1 tumor immunotherapy treatment and required systemic therapy (systemic therapy); (2) Patients with RET mutant medullary thyroid carcinoma (MTC) who have undergone prior treatment and have no acceptable alternative treatment options and require systematic treatment; (3 ) Patients with advanced RET fusion-positive thyroid cancer who have progressed after receiving other programs and have no acceptable alternative treatment programs and require systemic treatment.

In 2019, the FDA granted selpercatinib orphan drug status for the treatment of: RET fusion-positive NSCLC, RET fusion-positive, and RET mutant thyroid cancer, including poorly differentiated thyroid cancer, undifferentiated or anaplastic thyroid cancer, MTC, locally advanced or metastatic follicular or papillary thyroid cancer.

In December 2019, Lilly launched two phase III trials of selpercatinib: the LIBRETTO-431 trial was used to treat patients with newly treated RET fusion positive NSCLC, and LIBRETTO-531 was used to treat patients with newly treated RET mutation MTC. Each trial will recruit 400 patients.

Source: Lilly Receives FDA Priority Review for the Selpercatinib New Drug Application

Article link: http://news.bioon.com/article/6749731.html