After a few long years of watching from the sidelines as its rivals dove into immuno-oncology’s most coveted market, AstraZeneca finally has a study win in previously untreated non-small cell lung cancer.
Monday, the British drugmaker said that both a pairing of Imfinzi plus chemo and a combination of Imfinzi, CTLA4 candidate tremelimumab and chemo outperformed solo chemo at keeping patients’ cancer from progressing. Just how long the regimens kept disease at bay remains to be seen; those details won’t come out until a future medical meeting. But in the meantime, AZ will be sharing them with regulators, it said.
The study victory is an important one for AstraZeneca, which hadn’t previously been able to show that the Imfinzi-tremelimumb combo could get it done in the first-line setting. The company failed to get in on the ground floor thanks to a big miss in its all-important Mystic study back in 2017, and this past August, the duo flopped another trial pitting it against standard-of-care chemo.
But just how much of a difference the latest study—called Poseidon—will make in the market isn’t clear. Merck’s Keytruda-chemo combo has been cleaning up ever since the New Jersey drugmaker showed it could slash the risk of death by half, setting an extremely high bar for its rivals. And AstraZeneca doesn’t even yet have confirmation that its tandem can prolong lives; those are data it expects to read out in 2020.
The way Wolfe Research analyst Tim Anderson sees it, showing that overall survival benefit "will be required" to snag regulatory approval for both the doublet and the triplet. And "equally important, positive OS results will be needed for both the doublet and the triplet to be commercially relevant," he wrote in a Monday note to clients, adding that commercially, the combos "may not add very much."
With the triplet, AstraZeneca will also have to show a large enough benefit to justify adding a third drug into the mix. Doing so often ups toxicity levels for patients, not to mention the added costs—though the company was quick to note in its press release that "the triple combination delivered a broadly similar safety profile to the Imfinzi and chemotherapy combination and did not result in increased discontinuation of therapy."
Those are the same concerns analysts broached earlier this month, when fellow PD-1/PD-L1 drugmaker Bristol-Myers Squibb unveiled a win for its own cocktail of Opdivo, CTLA4 drug Yervoy and chemo. But that trio has already proven it can extend lives, and it also involves a shorter course of chemo than AstraZeneca’s regimen does.
"In our view, Poseidon results will most likely not be as compelling when compared side-by-side" to Merck's and Bristol's, Anderson wrote. "Recall that MRK’s KN-189 (IO+chemo doublet) hit at the interim (on both PFS and OS), for example—Poseidon did not. Similarly, BMY’s CM-9LA (IO+IO+chemo triplet) also hit at the interim (on both PFS and PS)—Poseidon did not."
Only time will tell. For now, AZ is highlighting some positive differentiators: Poseidon enrolled patients with squamous and non-squamous forms of NSCLC and used multiple choices of chemo regimen, increasing potential options for doctors.