FDA surprises everyone with super-fast Opdivo lung cancer approval

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).

Broad acceptance

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.

To contact the writer of this story email Amy Brown in London at AmyB@epvantage.com or follow @AmyEPVantage on Twitter

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