Drama as Roche's Tecentriq fails in key bladder cancer trial

Roche has been shocked by the late-stage trial failure of its immunotherapy Tecentriq in bladder cancer, a setback which could cost it billions if the drug loses its licence.

Roche was testing Tecentriq (atezolizumab) in people with locally advanced metastatic urothelial cancer whose disease had progressed during or after platinum-based chemotherapy, but has now failed to show overall survival benefit (OS) in a phase 3 trial.

The FDA conditionally approved Tecentriq based on the phase 2 IMvigor 210 study, which meant the Swiss pharma's phase 3 IMvigor 211 study needs a subsequent trial to confirm its efficacy in order for the drug to retain its US licence in bladder cancer.

But the failure to meet its primary endpoint of overall survival compared with chemotherapy means this hasn't been achieved.

Tecentriq has plenty of rivals in bladder cancer ready to exploit this slip-up: AstraZeneca’s Imfinzi (durvalumab), and only yesterday, Pfizer/Merck KGaA’s Bavencio (avelumab) are approved in this indication, though currently have similar conditional approvals.

Roche must now discuss what to do with the FDA, which will also be under scrutiny. A mishandling of the issue by the agency could undermine confidence in its accelerated access programmes, including the Breakthrough Therapy Designation, through which Tecentriq was fast-tracked in this indication.

Dealing with the issue will be a test for Richard Pazdur, the FDA oncology head who has led the development of the BTD and other programmes. Scott Gottlieb was yesterday confirmed as the FDA's new Commissioner, but hasn't yet been sworn in, so won't yet be able to influence the review.

Roche noted that there had been better than expected results in the trial’s chemotherapy arm, although full data will be presented later this year.

Roche’s chief medical officer, Sandra Horning, put a brave face on the results, saying the company believes “Tecentriq will continue to play an important role in the treatment of people with advanced bladder cancer.”

But Kepler Cheuvreux analyst David Evans said in a broker note, cited by Reuters, that “this puts the existing US bladder cancer approval in serious doubt, and will also, of course, raise concerns about Tecentriq’s efficacy in other cancer types.”

Reuters cited Deutsche Bank analysts who said that the failure placed up to $1 billion in peak sales at risk, while commentators on twitter were also surprised by the results

https://twitter.com/adamfeuerstein/status/862235419135660032

https://twitter.com/JacobPlieth/status/862208839961239553

Shares in Roche ticked down following the announcement, reflecting the importance of Tecentriq to the company.

It is trying to find a new generation of blockbusters as its trio of multi-billion sellers Herceptin, MabThera, and Avastin look likely to face cheaper biosimilar competition in the coming years.

Jefferies Equity Research has suggested peak sales as high as $12.7 billion for Tecentriq – but failure to maintain a licence in this key early indication would undermine confidence in the drug and place the sales in jeopardy, as the cancer immunotherapy market is becoming increasingly competitive.

The shock results have echoes of what happened to BMS' Opdivo, when it failed to show efficacy in lung cancer last year. However Roche's position is far worse, as Opdivo was not already approved in the indication.