Pressure mounts on Bristol-Myers, AstraZeneca as Merck bags Keytruda chemo combo approval

New Keytruda image
Merck's Keytruda now boasts two approvals in first-line non-small cell lung cancer.

Your move, Bristol-Myers Squibb and AstraZeneca. The FDA has blessed Merck & Co.’s Keytruda-chemo combo in first-line lung cancer—and now it’s up to BMS and AZ to prove their rival combo approach is viable, too.

The FDA late Wednesday green-lighted Merck’s checkpoint inhibitor Keytruda in tandem with Eli Lilly’s Alimta as a regimen for previously untreated patients with non-squamous non-small cell lung cancer.

The go-ahead “helps strengthen/preserve Merck’s leadership” in first-line patients, Bernstein analyst Tim Anderson pointed out in a note to clients. Keytruda’s solo approval in previously untreated patients covers only those with PD-L1 expression levels above 50%, and that group makes up just 25% to 30% of the addressable population, he wrote.

RELATED: Merck's Keytruda wins coveted first-line lung cancer nod, cementing rise 'from laggard to leader'

Merck first snagged that leadership last year after then-top dog and archrival Bristol-Myers flopped a first-line monotherapy trial with its own checkpoint med, Opdivo. Now, Keytruda boasts two first-line nods to Opdivo’s zero.

The pressure on Bristol-Myers doesn’t end there, though. Merck’s approval also marks “the first true endorsement of the general ‘chemo combo’ approach,” which Roche is also pursuing with its contender Tecentriq. What is “not yet clear” is how Bristol-Myers and AstraZeneca’s efforts to pair their PD-1/PD-L1 meds with CTLA4 treatments—such as BMS' own Yervoy—will stack up, Anderson noted.

RELATED: Another Opdivo setback for Bristol, this time on the combo front, widens Merck's immuno-oncology lead

While it won’t be long before industry watchers have data to compare—results from AstraZeneca’s Mystic trial, which is examining the British drugmaker’s Imfinzi in combination with CTLA4 candidate tremelimumab, should read out in June or July—plenty will still be up in the air even then, Anderson cautioned.

If the CTLA4 duo from either AZ or BMS “ends up looking better/worse than Merck’s chemo combo, if Roche’s different chemo combo looks better/worse than Merck's chemo combo, or even if the data from Merck's larger phase 3 chemo combo trial looks more/less impressive" than its earlier data "then this will have direct implications on how we model Keytruda going forward,” he wrote.

His forecasting solution? Hold off on tweaking Keytruda predictions, at least for now.

Meanwhile, while Merck’s new approval is an obvious positive, it does have some limitations. Alimta-based chemo regimens are used in just 25% of first-line patients in the U.S., and non-squamous patients represent just 75% of the broader first-line NSCLC pool, Anderson wrote.