Editor's Corner—Notes on a crazy 2 weeks that transformed immuno-oncology

It’s been just a couple of weeks since we wrote up AstraZeneca’s Imfinzi approval in bladder cancer. But so much has happened in the immuno-oncology field over that short stretch that, frankly, we at FiercePharma aren’t sure we even recognize the field anymore.

Let’s recap. Early on May 1, there were just two players with checkpoint meds approved in urothelial carcinoma—Roche, which last year was first into the market with Tecentriq, and Bristol-Myers Squibb, which entered just this February with a go-ahead for Opdivo.

Now, though, thanks to a pair of accelerated FDA approvals, there are four: Imfinzi, and Pfizer and Merck KGaA’s Bavencio, have jumped into the fray, making bladder cancer the most competitive I-O arena yet. It features every PD-1/PD-L1 checkpoint med the FDA has ever approved—save Merck’s Keytruda, which is currently vying for a green light.

Last week, however, a key failure for Tecentriq in previously treated bladder cancer patients put all of those drugmakers on notice. After snagging its FDA go-ahead with durable response data, the Roche trailblazer failed to prove it could actually extend patients’ lives. Now, the company faces the prospect of the FDA wiping the indication—which accounts for 70% of Tecentriq’s current sales—off the med’s label.

And its nemeses, all of which have either won indications or submitted applications based on durable response data, are seriously hoping the same fate doesn't befall them. Since filing its Keytruda materials, Merck, for its part, has added overall survival data that regulators are currently reviewing. But the other drugmakers are still in phase 3 trials and crossing their fingers their meds can post survival wins.

Meanwhile, speaking of Merck, the New Jersey drugmaker got a significant regulatory lift last week with a new FDA approval of its own. The agency gave the thumbs-up to its Keytruda-plus-chemo pairing in first-line lung cancer, a combo indication Roche, Bristol and AstraZeneca all are pursuing. 

AZ and Bristol, though, are doing it their own way—combining their meds with CTLA4 meds, instead of the chemo drugs Merck and Roche are adding (or hoping to add) to their PD-1/PD-L1 products. So, while the FDA win gave the latter two drugmakers some validation for their chemo-combo strategies, it also upped the ante for the former two, whose data will have to come up big if they want to compete.

This isn’t a bad time to mention that AZ and Bristol's CTLA4 combo data will directly affect any takeover action they face down the line. Earlier this week, media reports said Novartis could sell GlaxoSmithKline its stake in the consumer health joint venture they share, netting more than $10 billion to spend on an AstraZeneca buyout. And industry-watchers have speculated that Pfizer could have its eye on Bristol—but it doesn’t make sense to go for the buy until Pfizer has some answers on the CTLA4 tandem (also known as Opdivo-Yervoy). Pfizer chief Ian Read himself pointed out on a call earlier this month that “certain large companies have significant, almost binary risks … which could immediately alter their values.” No pressure.

AZ, however, did get some much-needed validation late last week with news that Imfinzi had hit its primary endpoint in the company’s Pacific trial, which is testing the med as a maintenance therapy in surgery-ineligible patients with stage 3 non-small cell lung cancer. The results went “some way toward securing” AstraZeneca’s “I-O bogey,” Bernstein analyst Tim Anderson wrote in a note to clients, and in a bigger-picture kind of way, they also showed that “I-O has a place in non-metastatic disease.”

“Pacific is the kind of breakthrough that promises to pull upward on the I-O market size,” he said. In other words, it's a big deal for everyone involved.

Still with us? Good. As Anderson put it last week, “by now, investors are (or should be) accustomed to I-O surprises,” and we couldn’t agree more. And as more players enter the field—and target more tumor types—the potential for the unexpected to occur will only keep growing.

Of course, we at FiercePharma will follow along closely to make sure you get all the necessary updates. And at this rate, it likely won’t be long until the next batch rolls in. ASCO, anyone? — Carly Helfand | email/Twitter