FDA starts speedy review of Loxo’s site-agnostic cancer drug larotrectinib

Loxo CEO Joshua Bilenker
Loxo CEO Joshua Bilenker (Loxo Oncology)

Loxo Oncology is preparing for a November verdict from the FDA on larotrectinib as a treatment for solid tumors carrying a specific mutation—regardless of where they appear in the body.

The Bayer-partnered drug has just been awarded a priority review by the regulator for locally advanced or metastatic solid tumors harboring a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, with a target action date of Nov. 26.

Larotrectinib—a pan-tropomyosin receptor kinase (TRK) inhibitor—ties in with a trend among cancer drugs seeking approval based on a molecular target or biomarker, rather than the organ or tissue in the body where the tumor originates.

Merck & Co. was the first to claim an FDA approval on that basis, getting a green light for its checkpoint inhibitor Keytruda (pembrolizumab) in microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors last year.

Loxo’s CEO Josh Bilenker said on a recent conference call that the company is preparing for a potential launch later this year, while Bayer says it plans to file for approval of larotrectinib in Europe before the end of the year. The German drugmaker licensed rights to the drug and follow-up LOXO-195 last November for $400 million upfront plus over $1 billion more in milestones.

Meanwhile, the company will be presenting new data on another biomarker-targeted cancer drug—RET inhibitor LOXO-292—at the 2018 ASCO Annual Meeting next month.

The eventual success of Loxo’s NTRK and RET candidates clearly depends on patients being screened for their respective biomarkers in the first place, and to that end Loxo formed an alliance with diagnostics and gene sequencing specialist Illumina last year to develop a tumor-profiling test that can be carried out on a patient biopsy or surgical specimen.

The aim is to develop a broad screen that takes in the majority of tumor biomarkers tied to a reimbursement pathway, which would avoid relying on a specific diagnostic for a rare mutation, which could be a drag on uptake. Bilenker thinks that sort of screening approach will be critical for site-agnostic cancer drugs to be successful commercially.

There are promising signs toward that vision. Earlier this year, the Centers for Medicare & Medicaid Services issued a national coverage decision for genomic profiling that suggests there is an appetite to make this type of testing available more widely to cancer patients, which could filter through to payers.

Larotrectinib has also been granted a breakthrough-therapy designation by the FDA. It’s one of a handful of NTRK drugs coming through the pipeline including Ignyta’s entrectinib—which targets both NTRK and Ros1 and prompted a $1.7 billion buyout of the company by Roche last year—and earlier-stage candidates such as TP Therapeutics’ ALK/Ros1/NTRK drug ropotrectinib, which will also feature at ASCO.