Merck & Co has halted a phase III trial of Keytruda in bladder cancer early after seeing a clear survival benefit, while the FDA has started its review of Bristol-Myers Squibb’s Opdivo in that indication.
The two developments mean that Roche’s privileged position as the only PD-1/PD-L1 inhibitor approved for bladder cancer could be short-lived, and comes soon after Roche’s drug encroached on its rivals’ territory with a US approval in non-small cell lung cancer (NSCLC).
Merck reported the results of the KeyNote-045 trial in urothelial carcinoma – the most common form of bladder cancer – just ahead of the weekend, saying that Keytruda (pembrolizumab) was more effective than chemotherapy at extending patients’ lives when given as a second-line therapy.
The trial compared Keytruda to the investigator’s choice of chemotherapy agents – paclitaxel, docetaxel or vinflunine – and showed that Merck’s drug improved both progression-free survival (PFS) and overall survival.
Bladder cancer has proved to be remarkably resistant to new drug therapy. The standard of care remains cisplatin and there have been few treatment advances over the last 30 years, so immuno-oncology agents are expected to make swift and dramatic headway both in the second- and first-line treatment settings.
Also on Friday, BMS confirmed that the FDA had accepted its marketing application for Opdivo (nivolumab) as a second-line treatment for advanced urothelial carcinoma after platinum-based chemotherapy, setting it on course for approval by the beginning of March 2017. The EMA started its review for the EU market in September.
There has been no word yet on filing plans for Keytruda, but Merck’s head of R&D Roger Perlmutter said the company is looking forward to “sharing the findings from this study with the medical community and with regulatory authorities around the world”.
Tecentriq (atezolizumab) has got off to a strong start in the market since it was first approved for bladder cancer in May, making sales of just under $100m in second and third quarters of the year, and is expected to gather momentum after its approval last week in second-line NSCLC.
So far, Opdivo has been firmly in the lead among the PD-1/PD-L1 inhibitors, but stumbled as a first-line treatment for NSCLC, giving an opportunity for Merck and Roche to close the gap. Merck is waiting on an FDA decision for Keytruda as a first-line NSCLC therapy in patients whose tumours express PD-L1 by 24 December.
Neither BMS nor Merck have reported third-quarter results yet, but in the first six months of the year sales of Opdivo came in at $1.54bn, while Keytruda added $563m to Merck’s top-line in the same period.
Analysts see Opdivo maintaining its lead in the market despite the setback, with Sanford Bernstein analyst Tim Anderson predicting BMS’ drug will have 2021 sales of $8.1bn, ahead of Keytruda with $6.5bn and Tecentriq on just below $5bn.