Roche’s Tecentriq wasn’t supposed to fail its phase 3 trial in second-line bladder cancer. But that’s what it just did—and the data shortfall not only endangers the drug’s conditional FDA approval, but could augur trouble ahead for other checkpoint inhibitors that followed Tecentriq into the field.
Tecentriq, approved last year on the basis of phase 2 data showing a durable response to the drug, failed to prove it could actually prolong patients' lives, the company said Wednesday. The bladder cancer indication, Tecentriq’s first, accounts for about 70% of the med’s current sales, analysts say, and the FDA could well decide to strike that approval off the drug’s label.
“[W]e assume that this will put this indication at risk of being removed from the label,” Leerink analyst Seamus Fernandez wrote Wednesday morning, noting that the results were unexpected. “This comes as a surprise to us, considering Merck’s Keytruda showed an overall survival benefit.”
Bad for Roche, though not as bad, in itself, as it might appear. But even more so, and more broadly, the trial failure could trigger concerns that the PD-L1 mechanism Tecentriq uses, as does two of its rivals, falls short of the PD-1 meds in the same checkpoint class.
Even more broadly, it’s raising questions about all of Tecentriq’s bladder cancer competitors. Though it was first in the PD-1/PD-L1 class to win an FDA nod in bladder cancer, since then, Big Pharma rivals have piled in: Bristol-Myers Squibb’s Opdivo, AstraZeneca’s newly minted Imfinzi (durvalumab), Pfizer and Merck KGaA’s Bavencio (avelumab), which just nabbed its bladder cancer nod this week, and Merck & Co.’s Keytruda, now under FDA priority review for the indication.
As Anderson pointed out in his investor note, all of those medicines won bladder cancer nods, or submitted applications, based on durable response, rather than survival data. Keytruda has since posted overall survival data that’s under review at the FDA. The rest are in phase 3 trials aiming for survival data of their own—which means the Tecentriq failure could signal trouble ahead for the group.
“Until now, IO has moved from success to success across oncology, besting conventional chemotherapy in the second-line setting wherever challenged,” Anderson said. “Does this mark a limit? If so, all the other manufacturer's bladder programs are at risk.”
Maybe, maybe not. Evercore ISI analyst Umer Raffat said in a Wednesday note that the overall response rates used for approval vary across the class, with Opdivo, for one, showing an edge over Tecentriq and Bavencio.
But, he said, “we also acknowledge that we do not have full visibility into duration of response and its still unclear how [overall response rate and durable response] correlates with survival.”
For what it’s worth, Opdivo (with its higher overall response rate) and Keytruda (with survival data in hand) are PD-1 meds, while Tecentriq, Bavencio and Imfinzi are on the PD-L1 side of the fence.
Roche is doing some damage control; as Anderson writes, the company appears to be trying to “squash speculation” that Tecentriq, and perhaps its PD-L1 peers, “might be a lesser product/mechanism” than the current PD-1 leaders in that class.
For its part, Roche says the latest data, from a study called IMvigor211, isn't as big a departure from the results of a previous study, IMvigor210, when comparing similar types of patients.
"Results observed in people treated with Tecentriq in IMvigor211 were generally consistent with those observed in a similar group of people in the Phase II IMvigor210 study," the drugmaker said in an emailed statement.
Tecentriq has other approvals in hand, including a use in previously untreated bladder cancer patients who can’t use cisplatin chemo and in second-line non-small cell lung cancer. And Roche obviously plans to persevere in bladder cancer.
“While these results are not what we had expected, we believe that Tecentriq will continue to play an important role in the treatment of people with advanced bladder cancer,” said Sandra Horning, chief medical officer at Roche. “We are committed to helping people with advanced bladder cancer and will discuss these data with health authorities.”
Editor's note: This story was updated with a statement from Roche's Genentech business and with correct information about Keytruda's status in bladder cancer.