Eli Lilly Submits IND Application for RET Inhibitor LOXO-292 (Selpercatinib) in China

Source: PharmaCube Info

Original: Vernacular Chinese

On September 26, the CDE website showed that Eli Lilly’s RET inhibitor LOXO-292 was submitted for clinical trial application in China, marking the first time the drug has been applied for clinical trials in the country. Additionally, Eli Lilly plans to submit a New Drug Application (NDA) for LOXO-292 to the FDA by the end of 2019.

LOXO-292 (Selpercatinib) is a highly specific oral RET inhibitor developed by Loxo Oncology for the treatment of tumors harboring RET gene fusions or activating mutations. RET fusions and mutations occur in various tumor types, including lung cancer, thyroid cancer, and several other malignancies. It is estimated that RET gene fusions occur in approximately 1%–2% of patients with non-small cell lung cancer (NSCLC), in 10%–20% of patients with papillary thyroid cancer (which accounts for approximately 85% of all thyroid cancers), and in approximately 60% of patients with medullary thyroid cancer.

In January 2019, Eli Lilly acquired Loxo Oncology for $8 billion to obtain this targeted therapy. At the recently concluded WCLC 2019 conference, Eli Lilly first announced positive Phase I/II LIBRETTO-001 clinical data for LOXO-292 monotherapy in RET fusion-positive non-small cell lung cancer (NSCLC).

The results showed that treatment with LOXO-292 achieved an objective response rate (ORR) of 68% in patients who had received multiple prior therapies, including a complete response (CR) rate of 2%. Additionally, up to 50% of patients with RET fusion-positive non-small cell lung cancer (NSCLC) may develop brain metastases, and LOXO-292 treatment yielded a central nervous system (CNS) ORR of 91% in these patients, with a CR rate of 18%. In treatment-naïve NSCLC patients with RET gene fusions, Eli Lilly’s LOXO-292 also achieved an ORR of 85%.

Currently, LOXO-292 has been granted Breakthrough Therapy Designation by the FDA for three indications, including the treatment of non-small cell lung cancer (NSCLC) with RET gene fusions, thyroid cancer, and medullary thyroid cancer (MTC) with activating RET gene mutations.

Eli Lilly plans to submit a New Drug Application (NDA) to the FDA by the end of this year, while simultaneously conducting two Phase III clinical trials to evaluate the potential of selpercatinib in combination with other therapies as first-line treatment for non-small cell lung cancer (NSCLC) harboring RET fusions and medullary thyroid cancer with RET-activating mutations. Additionally, at the ESMO 2019 Congress held from September 27–30, Eli Lilly will continue to present data on selpercatinib in the treatment of thyroid cancer.

Another highly anticipated investigational RET inhibitor is BLU-667, developed by Blueprint Medicines. On June 6, 2018, CStone Pharmaceuticals entered into a collaboration with Blueprint Medicines, acquiring the development rights in China for three drugs, including BLU-667, for a total transaction value of $386 million. On August 12, 2019, CStone announced that the first Chinese patient had been enrolled in the global Phase I registrational study of BLU-667.

At the recently concluded CSCO 2019 Congress, Blueprint Medicines announced for the first time the data from the medullary thyroid cancer (MTC) cohort of the ARROW study on BLU-667, and also updated the data from the non-small cell lung cancer (NSCLC) cohort. The results showed that among 48 MTC patients with measurable lesions who had undergone at least one follow-up assessment, the objective response rate (ORR) to BLU-667 was 58%, and the disease control rate (DCR) was 96%. Among 35 patients with RET fusion-positive NSCLC who had previously received platinum-based chemotherapy, the ORR was as high as 60%, the DCR reached 100%, and the treatment demonstrated good tolerability.

Currently, the FDA has granted BLU-667 Breakthrough Therapy Designation for the treatment of RET mutation-positive medullary thyroid cancer (MTC). Blueprint plans to submit a New Drug Application (NDA) to the FDA in Q1 2020 for the use of BLU-667 in patients with RET fusion-positive non-small cell lung cancer (NSCLC) who have previously received platinum-based chemotherapy, and intends to submit an NDA to the FDA in the first half of 2020 for the treatment of patients with RET-mutant MTC who have previously been treated with approved multikinase inhibitors (MKIs).