Eli Lilly is doubling down on novel mechanisms of action to steer clear of the “pile-on effect” seen in PD-1/PD-L1 and other hot targets. The Big Pharma wants to hightail novel approaches into the clinic and up to proof of concept before its rivals—and then kill off programs that fail to wow in phase 2.
The outgoing and incoming presidents of Lilly Research Laboratories—Jan Lundberg, Ph.D., and Dan Skovronsky, M.D., Ph.D., respectively—outlined the plan in a conversation with analysts at Bernstein.
As Skovronsky sees it, Lilly had a chance to be the first to win approval for drugs aimed at a clutch of exciting targets, including CDK 4/6, IL-17, IL-23, PCSK9 and CGRP. But instead of quickly advancing the programs out of its labs and into the clinic, Lilly hesitated, allowing rivals to leapfrog it and in some cases force it out of the race altogether.
Skovronsky diagnosed the problem as stemming from Lilly being too slow to take the assets into human testing. The incoming research chief wants that tentative approach to end on his watch.
“We want to be the first testing novel mechanisms. You should see more Lilly phase 1 trials and proof of concept trials on novel mechanisms,” Skovronsky said.
Once in the clinic, Skovronsky is tasking Lilly with hurtling headlong to the proof-of-concept go/no-go decision and acting decisively once it has data. That is the often unfulfilled aspiration of many drug developers, which drop the ethos when faced with equivocal data in the belief it is better to give an asset one too many chances than one too few. Skovronsky’s doesn’t think that will cut it anymore.
The incoming president wants Lilly to test drugs with novel mechanisms of action in small phase 2 trials. If the trial shows a large effect size, the drug will advance. Any assets that fall short of that goal will find themselves on the scrapheap. Lilly will move onto the next mechanism rather than “try and eke out an OK drug,” Skovronsky said.
Skovronsky’s attitude is underpinned by a belief the days of me-too drugs and marginal gains being a viable strategy are over. That thinking led Lilly to hang a for sale sign on two-thirds of its midphase cancer pipeline last year. And in theory, it should mean Lilly stays clear of the scrums that develop around some targets, either because it is out in front or never joins the race.
“What I see as one of the challenges now is this pile-on effect that is obviously best exemplified in the PD-1/PD-L1 access where there are just too many companies working on the same target too late in the game. That is not an efficient use of resources for shareholders or for patients,” Skovronsky said.
In trying to take the road less traveled, Lilly will continue to supplement the output of its own labs with assets bought in at or near late-phase development. But Skovronsky also wants Lilly to come to the deal table sooner and buy in earlier-stage, higher-risk programs that feed its appetite for novel technologies.