ViewPoints: AstraZeneca's key cancer hopefuls gain regulatory momentum

When AstraZeneca presents its third-quarter results early next month, investors will be keen to gauge management's tone towards pending results from the MYSTIC trial. This study – which is assessing the combination of Imfinzi and tremelimumab in first-line non-small-cell lung cancer (NSCLC) – missed its progression-free survival endpoint in July, but could still demonstrate an overall survival benefit when final data are presented early next year.

In an interview with the Financial Times published on Monday, however, CEO Pascal Soriot appeared to play down the chances of MYSTIC delivering an OS benefit, noting that "we think the probability for (the) combo (treatment) has really dropped quite a bit."

With MYSTIC, Bristol-Myers Squibb's Checkmate-227 trial – which is studying a similar PD-(L)1 plus CTLA-4 inhibitor combination – will largely determine whether this particular pairing of mechanisms has a future in the lung cancer market. Particularly so as rivals Merck & Co. and Roche have prioritised combinations that pair a PD-(L)1 inhibitor with chemotherapy, for which pivotal-stage data are also expected over the next six months (ViewPoints: Merck & Co. may move the goalposts for key cancer trial, say analysts).

However, providing evidence that CTLA4 inhibitors should not yet be written off, Merck is hedging its bets by also studying its PD-1 inhibitor Keytruda with Bristol-Myers Squibb's Yervoy, it was confirmed last week (ViewPoints: More clinical pivoting from Merck & Co. in lung cancer).

If Soriot is playing down the outlook for MYSTIC, it suggests the company is increasingly confident in alternative growth opportunities; as well it probably should be on the back of potentially practice-changing data readouts presented at the recent European Society of Medical Oncology (ESMO) congress.

See ESMO Spotlight: AstraZeneca delivers compelling riposte to MYSTIC setback with PACIFIC, FLAURA data and Spotlight On Interview: AstraZeneca strikes back.

And these clinical successes are now being reflected with regulatory momentum.

On Monday, AstraZeneca confirmed that Tagrisso – as a first-line therapy for EGFR-positive NSCLC – has been granted breakthrough therapy status by the FDA and also announced that its PD-L1 inhibitor Imfinzi has been accepted for review by the European Medicines Agency for the treatment of locally advanced unresectable NSCLC; the first regulatory submission for Imfinzi in the EU.

There will be some disappointment that the EMA did not sign off an accelerated assessment for Imfinzi in stage III NSCLC as AstraZeneca had requested, but the company can take heart from the fact it is well ahead of the competition in this particular space. There is little doubt that a second negative readout from MYSTIC in early 2018 would cast a shadow over AstraZeneca, but the company has done well with the PACIFIC and FLAURA datasets to size up opportunities where competition is notably reduced.

See also – Physician Views Poll Results: Oncologists' feedback on key lung cancer data from ESMO

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