I-O latecomers Pfizer and Merck KGaA fall further behind rivals with new lung cancer delays

Pfizer
Tweaks to Pfizer and Merck KGaA's first-line monotherapy trial of avelumab in lung cancer will set the pair back nearly two years.

Some industry watchers have wondered how much sense it makes for Pfizer to forge ahead with the immuno-oncology pact it has in place with Merck KGaA—and a new delay in the all-important lung cancer space is only triggering more questions.

The partners have tweaked the design of their trial evaluating candidate avelumab as a first-line monotherapy. Among the changes: The drugmakers changed the primary endpoint to include both progression-free survival and overall survival, and they'll be examining only patients with high PD-L1 expression, as opposed to those with any level. They're also boosting the number of study participants, which will more than double to 1095 from 420.

The changes were likely wise ones, “no doubt informed” by Bristol-Myers Squibb’s catastrophic first-line monotherapy flop with its own contender, Opdivo—as well as Merck’s success with its Keytruda, Bernstein analyst Tim Anderson wrote in a note to clients. Still, they’ll cost the companies nearly two years, with the trial wrap-up now slated for April 2019 instead of this August.

That’s not to say avelumab won’t see any earlier regulatory action in the lung-cancer space. Pfizer and Merck KGaA are still on track to file the candidate this year for approval in the second-line lung cancer space—but with Opdivo, Keytruda, Roche’s Tecentriq and AstraZeneca’s durvalumab advancing to the front lines of therapy, the second-line monotherapy commercial opportunity “is likely to be very small,” Anderson wrote.

Plus, BMS, Merck and Roche all already have second-line nods, meaning plenty of competition will already be ready and waiting when avelumab arrives.

There’s one more hitch, too: Avelumab, as Opdivo does, requires dosing every two weeks, while patients on Keytruda and Tecentriq can take three weeks between doses. That factor makes just a “modest difference commercially,” but it does still help to “tip the balance” in Merck and Roche’s favor, “all else being equal,” Anderson said.

Pfizer’s latecomer status to the checkpoint-inhibitor party has left some wondering if it might make more sense for the deal-hungry pharma giant to ditch Merck KGaA and nab one of its rivals instead. And with Bristol’s recent struggles taking a serious toll on shares, speculation has swirled that it could be a prime target.

Don't expect to see it happen anytime soon, though, Anderson cautioned. The way he sees it, it makes more sense for a buyer to wait and see if the company's first-line Opdivo-Yervoy combo approach is successful before pulling the trigger. "Only then will it become clearer how market shares will be allocated among the various participants," he noted.