Loxo buy a step closer to paying off as Lilly heads to FDA with RET inhibitor

Lilly could have the best-in-class and first-in-class RET fusion inhibitor as it heads to FDA this year with the lead asset in its $8 billion acquisition of Loxo Oncology Inc.

Eli Lilly and Co. (NYSE:LLY) announced data on Monday from the Phase I/II LIBRETTO-001 trial for selpercatinib (LOXO-292) to treat ret proto-oncogene (RET) fusion-positive non-small cell lung cancer (NSCLC) in patients who have relapsed after platinum therapy. Among 105 patients in the single-arm Phase II portion of the trial, the objective response rate (ORR) was 68%; in a subset of 11 patients with brain metastases, the ORR was 91%.

The benefit is consistent with Phase I data showing an ORR of 68% among 37 RET fusion-positive NSCLC patients.

At a June 17 data cutoff, the median duration of response in LIBRETTO-001 was 20.3 months and median progression-free survival was 18.4 months. Patients in the trial had a median of three prior systemic therapies; 55% had received either a PD-1 or PD-L1 inhibitor, and 48% had received at least one multikinase inhibitor. However, the ORR was similar regardless of prior therapy.

Among the Phase II population, nine patients (1.7%) discontinued therapy due to treatment-related toxicity.

The benefit was even greater among previously untreated patients.

Among 34 treatment-naïve RET fusion-positive NSCLC patients, selpercatinib showed an ORR of 85%. Median duration of response and median PFS were not yet achieved.

Lilly plans to submit an NDA to FDA this year based on LIBRETTO-001's data. Selpercatinib has breakthrough therapy designation for RET fusion-positive, previously treated NSCLC.

Blueprint Medicines Corp. (NASDAQ:BPMC) could be a fast follower with its RET fusion inhibitor pralsetinib (BLU-667), though it has shown a slightly lower response than selpercatinib thus far across all subgroups of NSCLC patients. At the American Society of Clinical Oncology (ASCO) meeting in June, data from the registrational Phase I/II ARROW trial showed that pralsetinib led to an ORR of 60% among 35 patients with previously treated RET fusion-positive NSCLC. Among the seven treatment-naïve patients, the ORR was 71%, and among nine patients with brain metastases who received pralsetinib, 78% had shrinkage of brain metastases (see "Pralsetinib ASCO Data").

Blueprint has said it will submit an NDA for pralsetinib in 1H20.

Selpercatinib was the driver of Lilly's buyout of Loxo, which closed in February (see "Lilly Acquiring Loxo").

About 2% of NSCLC patients harbor RET fusion mutations. Lilly said it plans to announce data for RET fusion-positive thyroid cancer, including medullary thyroid cancer, at the European Society for Medical Oncology (ESMO) meeting, which kicks off Sept. 27.

Blueprint slipped $4.79 to $73.17 on Monday.

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