US advisory committee backing for Lilly’s necitumumab presages the entry of a new treatment regimen for squamous non-small cell lung cancer, one in which the first-ever targeted agent is added to enduring chemotherapy regimens. So it may come as some surprise that it has such a modest forecast – just half a billion dollars in 2020.
What would have been seen as a noteworthy advance a couple of years ago is now viewed in the context of advancing immuno-oncology agents. Yet neci should not necessarily be underestimated: while the PD-1 drugs could enter this space, their effectiveness may not be broad enough to drive out all competitors.
Looking good for approval
The FDA’s comfort level with the Lilly antibody was expressed in the fact that there were no voting questions at yesterday’s meeting – rather, the experts were invited to discuss the risk-benefit profile based on the pivotal Inspire and Squire trials after presentations from the regulator and Lilly.
Significant, if modest, improvements in overall survival and progression free survival of 1.6 months and 0.2 months respectively, when compared to chemotherapy, should be sufficient to win approval in this first-line setting by necitumumab’s October FDA decision date, according to analysts from both Bernstein and Leerink Research. The regulator was focusing on an exploration of the elevated risks of blood clots and low levels of magnesium in the blood.
Since both are known side-effects of antibodies acting on the human epidermal growth factor receptor (EGFR), specialists likely to prescribe necitumumab are experienced in managing these risks. In any case, Lilly supported labelling that would ensure physicians and patients are aware of the risks to allow for appropriate prescribing, along with monitoring and steps to prevent adverse events.
While two drugs have been approved in the last seven months for patients who advance after chemotherapy, little progress has been made in first-line treatment. Abraxane was the most recent approval, in 2012, although since it is an albumin-bound formulation of paclitaxel it represents a modest advance. Patients had gone a decade without a single approval before Abraxane’s launch.
In second-line treatment, progress has been more brisk. Lilly’s own Cyramza won approval in December, followed by Bristol-Myers Squibb's Opdivo in March.
The last war
Opdivo, one of two FDA-approved anti-PD-1 products, is emblematic of the commercial limitations of necitumumab. Agency experts themselves suggested that necitumumab may represent a temporary improvement on the way to the more durable action of Opdivo and the other PD-1, Merck & Co's Keytruda. The former is forecast to achieve $4.3bn in sales in non-small cell lung cancer in 2020 and the latter $3.5bn if approved in the disease, according to EvaluatePharma’s consensus.
Whether they will meet those lofty estimates will become more apparent when key first-line lung cancer studies – Checkmate 026 for Opdivo and Keynote 024 and 042 for Keytruda – read out.
Those trials are all-comers on squamous and non-squamous histologies, but focus on patients who test positive for the PD-1 receptor, the mechanism through which the two products trigger an immune response to tumour cells. Bernstein analyst Tim Anderson notes that PD-1 blockade creates a durable response in only 30% of patients, leaving 70% of patients available for treatment with necitumumab.
That opportunity is worth $500m, according to EvaluatePharma’s consensus. So while necitumumab may make Lilly look like a general fighting the last war, it may be about to launch its second lung cancer drug in two years. For a group that went a decade without putting a potential blockbuster on the market, it is a sign that R&D once again may be paying off.