Roche has been poleaxed by the news that its immuno-oncology flagship drug Tecentriq failed a phase III trial in bladder cancer that was supposed to transform its earlier conditional nod into a full approval.
PD-L1 inhibitor Tecentriq (atezolizumab) was granted accelerated approval by the FDA for urothelial carcinoma (UC) – the most common form of bladder cancer – a year ago on the back of phase II data. The US regulator allows an early green light on the understanding that a phase III trial is carried out to confirm the mid-stage findings.
Now Roche has revealed that its phase III IMVigor 211 failed to meet the primary endpoint of extending overall survival compared with chemotherapy, which the company put down to an unusually high response rate for the chemo arm of the trial.
Roche targeted bladder cancer as its first indication for Tecentriq allowing it to launch without direct competition from Bristol-Myers Squibb and Merck & Co, the first companies to bringPD-1/PD-L1 inhibitors to market.
The tactic was a success allowing the drug to rack up sales of around $270m in its first 12 months on the market, split roughly two thirds to one third between bladder and lung cancer, its second major indication. More than $100m of that came in the first quarter of this year.
Now, Roche is facing the possibility that its conditional approval could be revoked at a time when other drugs in the class – BMS’ Opdivo (nivolumab), Merck KGaA/Pfizer’s Bavencio (avelumab), AstraZeneca’s Imfinzi (durvalumab) – have already claimed approvals in bladder cancer and Merck & Co’s Keytruda (pembrolizumab) is just weeks away from a regulatory verdict in that indication.
The failure leaves the FDA with a thorny problem. If it were to revoke Tecentriq’s second-line use in UC, the drug still has first-line approval for chemotherapy-ineligible patients with that type of cancer with confirmatory trial results (from the IMvigor130 study) not due until 2019, according to Leerink analyst Seamus Fernandez.
It’s worth noting that all the checkpoint inhibitors have been approved or sought conditional approval on the basis of phase II data showing tumour responses rather than survival data, although Merck has since published results for Keytruda showing a survival advantage.
With one win and one fail in confirmatory bladder cancer trials it’s hard to draw any conclusions about the implications of the IMVigor211 failure on the PD-1/PD-L1 inhibitors, other than to show they may have limitations – as witnessed by Opdivo’s spectacular failure in first-line non-small cell lung cancer (NSCLC) last year.
For now Roche is keeping quiet about what must have been a shocking revelation, other than to insist it Tecentriq’s role in bladder cancer isn’t finished.
“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 the company’s chief medical officer Sandra Horning.
“We are committed to helping people with advanced bladder cancer and will discuss these data with health authorities.”