US clinical hold on Astrazeneca’s immuno-oncology combination in head and neck cancer came as a nasty blow last month, but the group is not going down without a fight. Today its chief executive, Pascal Soriot, surprisingly left unchanged expectations of when data would be reported from the two currently halted trials.
This, plus an aggressive timeline to file the combo in lung cancer, shows Astra’s desperation to remain in the race. You can hardly blame it; the distant hope of a head and neck cancer filing based on phase II has evaporated, and a lacklustre third quarter has put even more pressure on oncology to carry the group through the lean times.
That quarter saw sales miss expectations as Astra was hit by the first full three months of generic competition to Crestor and pressures in diabetes, and only a one-off tax benefit allowed it to beat consensus earnings forecasts.
One way to support the bottom line is by aggressively cutting administrative spending. “We will continue our work to increase productivity and manage SG&A down as best we can, and we are on a continuous programme of productivity improvement,” Mr Soriot told today’s third-quarter media call.
However, in the longer term Astra also needs sales to recover, and the partial clinical hold on the Kestrel and Eagle head and neck cancer trials of durvalumab plus tremelimumab shows just how vulnerable it is in oncology – one of its three growth pillars (Astra’s combo strategy comes under pressure, November 3, 2016).
Recruiting ahead of timeline
But today the group made a point of stating that the two studies would yield data in the second half of 2017 and in 2018 respectively – an unaltered timeline – despite the clinical hold. “We were recruiting ahead of our timeline, and we are confident we should be able to resume a fast pace of enrolment,” said Mr Soriot.
A response has been submitted to the FDA about the bleeding events that had caused the snafu, and investors will take the hint that the hold should be lifted soon. Astra’s chief medical officer, Sean Bohen, added: “The timeline is dependent on event rate ... should our event rate prediction be accurate we’ll stick with the timeline.”
Still, Astra confirmed that a phase II head and neck cancer study, Hawk, was not registrational, though hopes that it could have been used for filing were only ever a pipe dream; Merck & Co’s Keytruda is approved in this cancer type, and Bristol-Myers Squibb’s Opdivo is awaiting registration.
The race is also on in lung cancer, where Astra said it would report durvalumab plus tremelimumab data from Mystic, a first-line trial, and Arctic, a third-line study specifically in PD-L1-negative patients, in the first half of next year. This would set up a filing in the second half.
The opening in first-line NSCLC and in low PD-L1 expressers appeared after the failure of Opdivo plus Yervoy in Checkmate-026. However, it will not be plain sailing for Astra: not only does it have to generate a positive result where Bristol failed, it must also contend with competition from other agents whose first-line trials are being expanded to go after this unexpected opportunity.
|Selected durvalumab + tremelimumab trials|
|2nd-line, PD-L1+ve H&N cancer||Hawk||Data in house; not registrational||NCT02207530|
|2nd-line, PD-L1-ve H&N cancer||Condor||Fully recruited; data H1 2017||NCT02319044|
|1st-line H&N cancer||Kestrel||Partial clinical hold; data H2 2017||NCT02369874|
|2nd-line H&N cancer||Eagle||Partial clinical hold; data 2018||NCT02551159|
|1st-line NSCLC||Mystic||Fuly recruited; PFS data H1 2017; OS data 2018||NCT02453282|
|3rd-line, PD-L1-ve NSCLC||Arctic||Fully recruited; Data H1 2017||NCT02352948|
Astra’s growing reliance on oncology also spells good news for deal bankers, since Mr Soriot said the group was not about to slow its plan to sell off assets that did not fall within oncology, cardiovascular/diabetes and respiratory areas.
“More and more we have a company that is focused around those three pillars,” he said. “We’ll continue to partner products that don’t fit, and we will continue doing this over the next year or two.”