Lilly's RET Inhibitor Selpercatinib (LOXO-292) Receives FDA Priority Review, Awaiting Approval Decision in Q3

Recently, Eli Lilly and Company announced that its RET inhibitor selpercatinib (LOXO-292) has been granted Priority Review by the U.S. FDA, potentially accelerating approval for the treatment of patients with advanced RET fusion-positive non-small cell lung cancer (NSCLC), RET-mutant medullary thyroid cancer (MTC), and RET fusion-positive thyroid cancer.The FDA is expected to respond to the New Drug Application (NDA) in the third quarter of this year.

RET gene alterations include gene fusions and activating point mutations, which can lead to hyperactivation of the RET signaling pathway and uncontrolled cell growth. RET gene fusions occur in 2% of non-small cell lung cancers, 10–20% of thyroid cancers, and a small subset of other cancer types. Activating RET point mutations are present in 60% of patients with medullary thyroid cancer. Cancers harboring RET gene alterations rely primarily on the aberrant activation of this protein kinase to drive their proliferation and growth; therefore, these cancers are highly sensitive to RET inhibitors.

Selpercatinib is a highly selective and potent oral RET inhibitor acquired by Eli Lilly and Company through its acquisition of Loxo Oncology. It not only inhibits the native RET signaling pathway but also suppresses potential acquired resistance. It has been granted Breakthrough Therapy Designation and Orphan Drug status by the FDA for the treatment of patients with non-small cell lung cancer (NSCLC) harboring RET gene fusions, patients with medullary thyroid cancer (MTC) harboring activating RET mutations, and patients with advanced thyroid cancer harboring RET gene fusions.

Image source: Reference [2]

The submission of this new drug application is based on positive data obtained from the Phase 1/2 LIBRETTO-001 trial of selpercatinib in patients with RET-mutant lung cancer and thyroid cancer. According to previously published data, as of June 17, 2019, selpercatinib achieved an objective response rate (ORR) of 68% in patients with non-small cell lung cancer (NSCLC) who had received multiple prior therapies, including a complete response (CR) rate of 2%. Up to 50% of patients with NSCLC harboring RET gene fusions may develop brain metastases. In the subgroup of patients with brain metastases, selpercatinib demonstrated a central nervous system (CNS) ORR of up to 91%, with a CR rate of 18%. Regarding duration of response, the median duration of response (DOR) in this patient population was 20.3 months, and the median progression-free survival (PFS) was 18.4 months. As most patients remained progression-free or in response, these median values are expected to increase further with longer follow-up.

“We are pleased that the FDA has granted priority review for the New Drug Application of selpercatinib, which represents a significant step toward providing novel precision therapies to patients with RET-driven cancers,” said Anne White, President of Lilly Oncology. “We are highly encouraged by the positive momentum in the selpercatinib development program and look forward to delivering a transformative new treatment option for patients with RET-driven cancers as soon as possible.”

References:

[1] Lilly Receives FDA Priority Review for the Selpercatinib New Drug Application，Retrieved January 29, 2020, from https://www.biospace.com/article/releases/lilly-receives-fda-priority-review-for-the-selpercatinib-new-drug-application/

[2] Lilly Oncology Update at World Lung. Retrieved January 29, 2020, from https://investor.lilly.com/static-files/71602f34-5643-4c02-b50a-0af6a2733806

[3] Lilly Announces Positive Results for Selpercatinib (LOXO-292), Demonstrating a 68 Percent Objective Response Rate and Sustained Durability in Heavily Pretreated RET Fusion-Positive Non-Small Cell Lung Cancer. Retrieved January 29, 2020, from https://investor.lilly.com/news-releases/news-release-details/lilly-announces-positive-results-selpercatinib-loxo-292

Original Title: Eli Lilly’s RET Inhibitor Granted Priority Review, Expected to Be Approved in Q3 This Year

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