In a stunning setback, Roche says its top cancer drug Tecentriq failed a key PhIII study

Genentech put the A team on their PD-L1 checkpoint program for Tecentriq (atezolizumab), building a pipeline of combinations now in the clinic as they raced to an accelerated approval so they could begin marketing in the booming field. And this morning, Roche says that the drug failed the late-stage confirmatory study in bladder cancer, failing to significantly improve overall survival and delivering a blow that raises questions about the fate of this drug and their entire checkpoint R&D campaign.

Roche’s stock dropped 2% on the news.

What went wrong?

Sandra Horning

Roche says it is studying that now, but noted in its statement that the chemo arm of the study experienced an unusually high response that wasn’t expected by the multinational company. The accelerated approval — which the FDA noted could be yanked if the Phase III failed — was based on the smaller Phase II IMvigor210 study.

Now the FDA will have to review whether the drug should stay on the market, after Roche had already launched an intense marketing effort on bladder cancer that quickly pushed sales past the $100 million mark last quarter. Analysts have widely tapped this therapy as a future blockbuster, worth billions of dollars.

Seamus Fernandez, Leerink

“This puts the existing U.S. bladder cancer approval in serious doubt, and will also, of course, raise market concerns about Tecentriq’s efficacy in other cancer types,” Kepler Cheuvreux analyst David Evans wrote in a note to investors, according to a report in Reuters.

Count Seamus Fernandez at Leerink among the many analysts adjusting to the unexpected. He noted:

This comes as a surprise to us, considering MRK’s (MP) Keytruda (pembrolizumab; anti-PD-1) showed an OS benefit in its pivotal Keynote-045 trial. As IMvigor211 served as a confirmatory study for Tecentriq’s accelerated approval for second-line (2L) bladder cancer, we assume that this will put this indication at risk of being removed from the label. However, the drug also has accelerated approval for first-line (1L) patients who are ineligible for cisplatin based chemotherapy and the confirmatory trial for this population (IMvigor130) is ongoing, with results expected in 2019.

Initially approved as a second-line treatment for bladder cancer, a first at the time, the Roche marketing team hit the ground running. Tecentriq has been a central feature of CEO Severin Schwan’s strategy, helping him avoid expensive M&A deals as he looks to the R&D group to deliver new blockbusters. Roche followed up just a few weeks ago with the accelerated OK as a frontline therapy. The pharma giant had no plans to look back now. It certainly wasn’t expecting the possibility of a do-over.

Severin Schwan, Roche CEO

Tecentriq was the third PD-1/PD-L1 drug to reach the market, after Merck and Bristol-Myers Squibb pioneered the first approvals. Now there are 5 on the market, with Pfizer/Merck KGaA and recently AstraZeneca joining the pack. But while these drugs have offered new ways for substantial numbers of patients to fight cancer, they also continue to occasionally stun researchers with unexpected results. Bristol-Myers had to shake up its entire research organization after a key failure for Opdivo in lung cancer last year derailed their lead position in the field.

This new failure in bladder cancer, where several checkpoints are now available, raises questions for everyone working in checkpoint drug development. Coincidentally, Merck KGaA and Pfizer scored their own approval to sell Bavencio for bladder cancer on Tuesday. That OK was also conditional on their future success with confirmatory trials.

“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.”

Image: View of the Rhine River with the illuminated Roche Tower, Basel, Switzerland on April 24, 2017. Shutterstock

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