The pullback from RET inhibition

Lilly’s disclosure today that it was discontinuing the next-generation RET inhibitor LOXO-260 points to the quiet biopharma exodus from this once-promising mechanism. On one hand Lilly’s Retevmo has grabbed the lion’s share of first-line RET-mutant NSCLC patients, with the Libretto-431 trial backing the registrational Libretto-001 study, an achievement that saw off one competitor: Roche pulled out of a deal covering Blueprint’s approved RET inhibitor rival, Gavreto, a year ago. But there was once promise in next-generation inhibitors to treat patients who had relapsed on Retevmo or Gavreto, and according to the design of a phase 1 trial this was Lilly’s aim with LOXO-260. Other clinical discontinuations include Bristol Myers Squibb’s TPX-0046, derived from Turning Point and canned over adverse risk-benefit. Boston Pharmaceuticals was collaborating with Daiichi Sankyo on zeteletinib, and Helsinn with Taiho on vepafestinib, but neither now appears in pipelines. The only other western company working clinically on RET inhibition appears to be the private UK biotech Ellipses Pharma with EP0031, which showed ORRs of 81% in treatment-naive, and 70% in RET-experienced, Chinese patients in a Kelun-run trial. Last year’s AACR poster claimed responses in all four evaluable western NSCLC patients, three of whom were RET pretreated.

Beyond Retevmo and Gavreto: the clinical RET inhibitor pipeline

Note: *US/Europe study; all others are at Chinese hospitals. Source: OncologyPipeline.