Eagle and Mystic lead AstraZeneca’s cancer clear out 

AstraZeneca has cleared (PDF) a clutch of cancer programs from its clinical pipeline. The PD-L1 combination trials Eagle and Mystic led the clear out, and the immuno-oncology drugs tested in those studies feature heavily in the earlier-phase cull. 

Eagle and Mystic tested PD-L1 drug Imfinzi and CTLA-4 antibody tremelimumab in second-line head and neck cancer and first-line non-small cell lung cancer, respectively. The studies both missed overall survival endpoints late last year, signaling the end of AstraZeneca’s hopes of leapfrogging its cancer rivals. AstraZeneca has now formally dropped Eagle and Mystic, citing “safety/efficacy” as the reason.

The Imfinzi combination trials were the only mid- to late-phase programs targeted in the latest review of AstraZeneca’s pipeline. None of the seven other affected programs, all of which are in oncology, made it past phase 1.

AstraZeneca’s cull of the early-phase programs eliminated several other explorations of the efficacy of Imfinzi and tremelimumab in combination with other drugs. With AstraZeneca dropping anti-OX40 antibody MEDI0562, it has also kicked trials assessing its effect on solid tumors when combined with Imfinzi and tremelimumab to the curb. 

A similar fate befell TLR 7/8 agonist MEDI9197. AstraZeneca presented early clinical data on the drug in solid tumors in 2017 and subsequently began testing it in combination with Imfinzi. That study was terminated late last year. ClinicalTrials.gov lists the reason for the action as “company strategy,” while AstraZeneca’s pipeline update attributes it to “safety/efficacy.”

The cull of combination trials also affected a program that was assessing Imfinzi in combination with either tremelimumab or danvatirsen in diffuse large B-cell lymphoma. AstraZeneca is continuing to test the Ionis-partnered anti-STAT3 antisense therapy danvatirsen in other combinations and indications. But has dropped the lymphoma study, which was penciled in to run until 2023.

AstraZeneca again cited “safety/efficacy” as its explanation for the action. The only victim of the pipeline review to receive a different reason for discontinuation is MEDI1873, which AstraZeneca said it is dropping for “strategic” reasons. 

MEDI1873 is a GITR agonist fusion protein that AstraZeneca tested as a monotherapy in patients with advanced solid tumors. That trial wrapped up late last year, after which AstraZeneca decided to focus its time and money on other assets. Bristol-Myers Squibb, Incyte, Leap Therapeutics and Merck have other drugs targeting the tumor necrosis factor receptor GITR in early-phase development. 

The changes have left AstraZeneca with a slimmed down early-phase cancer pipeline. No new cancer projects entered phase 1 to replace the seven programs AstraZeneca eliminated in the quarter. The only new entries to the clinical pipeline were a LOX-1 antibody in development in cardiovascular disease and an inhaled JAK inhibitor for use in asthma. 

RELATED: Baselga takes helm of AstraZeneca’s cancer R&D as pharma rings in the new year with big changes

Also out is the MedImmune name, first reported by Endpts ealier in the week, as the Big Pharma looks to integrate its new R&D structure with its new leaders. AZ bought MedImmune 13 years ago but faced criticism for its near $16 billion spend on what was essentially vaccines; since then, it has tried to make the biologics arm the main face of its cancer R&D, but this too has't really paid off.

It never looked like it would be a Genzyme or a Genentech, and so the retiring of its name seemed inevitable when CEO Soirot changed up how its research was run at the start of the year, and after a series of high profile execs recently left.