Eli Lilly axes next-generation, resistance-busting RET inhibitor

Eli Lilly has axed its next-generation RET inhibitor. The Big Pharma pushed the candidate, LOXO-260, into the clinic to overcome acquired resistance to existing drugs such as its own Retevmo but has now pulled it from the pipeline before clearing phase 1.

RET fusions are found in around 2% of non-small cell lung cancer patients and 10% of people with papillary thyroid cancer. In the subpopulations, RET inhibitors such as Lilly’s Retevmo and Blueprint Medicines’ Gavreto—the drug Roche is walking away from—have improved outcomes but tumors can also acquire resistance, creating a need for molecules that maintain potency against mutations.

Lilly identified LOXO-260 as a molecule that could fit that bill. Researchers designed the drug to have activity against both solvent front and gatekeeper mutations, while still having the potency and selectivity of existing RET inhibitors.

The company shared preclinical data on the next-generation RET inhibitor project in 2021 and moved its chosen candidate, LOXO-260, into the clinic the following year. Lilly designed the trial to assess the effect of the molecule in people whose cancer progressed four months or more after starting on a selective RET inhibitor.

According to ClinicalTrials.gov, the study was supposed to enroll 110 people and keep going into 2026. While the government website, which was last updated in August, still lists the trial as enrolling, Lilly removed (PDF) the RET inhibitor from its pipeline as part of its fourth-quarter results this morning. LOXO-260 was the only new drug removed from the pipeline. Lilly also dropped Verzenio in prostate cancer. 

Lilly pulled LOXO-260 from its R&D pipeline at the end of a good year for its approved RET drug Retevmo. Sales of the product, which Lilly acquired in its $8 billion takeover of Loxo Oncology, rose 32% last year but the drug is still a long way from fulfilling blockbuster forecasts, only bringing in $253.6 million across 2023.