For those harbouring concerns about regulators’ abilities to keep up with drug makers’ rapid progress in proving the potential of the anti-PD-1 antibodies, the super-fast US approval of Opdivo in its second use should come as a relief.
Acting more than three months ahead of the official PDUFA deadline, the FDA yesterday gave the checkpoint inhibitor a green light in previously treated, metastatic, squamous non-small cell lung cancer. The approval represents a first in this tumour type and appears to have also taken Bristol-Myers Squibb by surprise – the company released a very brief statement in the afternoon announcing the news, following up with a full press release two hours later.
It revealed that the FDA had accepted the application for review on February 27, meaning that the regulator only took five days – including a weekend – to respond. This had been submitted as a rolling BLA so must have been little more than a case of dotting the i’s and crossing the t’s, but even so this speed is impressive. The drug did not even have breakthrough therapy designation in this setting.
The Checkmate-017 trial provided the basis of the approval – the phase II study was stopped early for efficacy in January, although final data only emerged yesterday. It showed a three-month survival benefit over Taxotere.
The regulator would also have already reviewed data from the Checkmate-063 trial, which studied later-stage squamous patients who had failed at least two lines of therapy. The impressive 41% one-year overall survival generated prompted a 9% or $8bn jump in Bristol-Myer’s market value last year (Bristol checkmates lung study and trades like a biotech, October 31, 2014).
The squamous histology, a particularly intractable type of this disease, represents only a quarter to a third of lung cancer cases. Opdivo’s broader utility in the much larger non-squamous setting will be elucidated by the Checkmate-057 study.
Many expect this second-line trial also to be stopped early for efficacy, maybe sometime in the first half of this year, a hotly awaited event. Should this happen Bristol-Myers will no doubt once again seek and expect swift regulatory endorsement.
The company can also anticipate very quick backing from the medical community – something that has been seen in melanoma, the first indication for the anti-PD-1 antibodies. Both Opdivo and Merck’s Keytruda are specifically indicated only in second-line settings in this tumour type, though both were endorsed earlier this year as first-line treatments by the influential National Comprehensive Cancer Network – meaning Medicare and most private insurers will reimburse them in this use.
Both drugs received compendia listing, despite the fact that Keytruda has yet to generate any first-line melanoma data. Opdivo demonstrated a clear survival benefit over chemotherapy in the Checkmate-066 study last November, but has not received regulatory backing for the setting.
This move by the NCCN is of course encouraging for all drug makers pursuing the PD-1 target, suggesting strong belief in the potential of this mechanism of action, and a willingness to pre-empt regulators – and sometimes data – for the benefit of patients. However it also suggests that scientists and physicians regard the PD-1 targeting antibodies – or at the very least Opdivo and Keytruda – as similarly effective.
The situation in lung cancer will not be exactly the same, particularly in the large first-line, non-squamous setting, where combination approaches will be key and much data are still awaited. But in later lines of therapy in both squamous and non-squamous settings it will be interesting to see whether a similar situation emerges.
Analysts at Bernstein commented today that Opdivo could achieve compendia listing in first-line squamous disease ahead of any FDA action, adding that this could even happen this year.
Bristol-Myers undoubtedly achieved a notable first with its lung cancer win but others are close behind – most notably Merck, which is expected to file Keytruda in both squamous and non-squamous histologies by mid-year. However, if nothing emerges in the coming months or years to differentiate these drugs, the small time advantages could come to mean little.