AZ immunotherapy gets FDA boost in early lung cancer

The FDA may have offered struggling AstraZeneca a lifeline, granting a “breakthrough” designation for its cancer immunotherapy Imfinzi in early-stage lung cancer.

AZ is reeling from poor results from the MYSTIC trial, which last week showed a combination of Imfinzi (durvalumab) and tremelimumab is only as good as existing drugs in first line lung cancer.

But the FDA’s decision smooths the way for a faster approval of Imfinzi monotherapy in patients with locally-advanced, unresectable non-small cell lung cancer, whose disease has not progressed after platinum-based chemoradiation therapy.

Shares in AZ were up 1.5% following the announcement, but this must be seen in the context of the massive 15% fall following the news late last week from MYSTIC, which wiped billions from the company’s value.

The Breakthrough Therapy designation was based on interim results from the phase 3 PACIFIC trial, which is testing Imfinzi as a sequential treatment in that indication.

Imfinzi has already gained the designation from the FDA for previously treated patients with advanced bladder cancer.

AZ is a latecomer to the cancer immunotherapy market, where Bristol-Myers Squibb and Merck & Co were trailblazers with PD-1 inhibitors Opdivo (nivolumab) and Keytruda (pembrolizumab), respectively.

Opdivo had an early advantage as it was first to market but Keytruda is catching up in sales after approval in the lucrative first-line lung cancer indication, where the BMS drug failed in a shock set of clinical trial results around a year ago.

Last week’s poor showing in the MYSTIC trial was the latest shock from a cancer immunotherapy, where trials have thrown up some unpleasant surprises.

Earlier this year a phase 3 trial failed to confirm the efficacy of Roche’s PD-L1 inhibitor, Tecentriq (atezolizumab) in advanced bladder cancer – raising doubts about whether the drug will remain on the market in that indication.

Imfinzi is seen as a key drug in AZ’s bid to revive sales following the patent expiries on former blockbusters Crestor and Seroquel XR.

It is also being tested in the adjuvant NSCLC setting in the ADJUVANT phase 3 trial. In the Stage IV 1st-line setting for patients with advanced NSCLC, Imfinzi as monotherapy and in combination with tremelimumab, an anti-CTLA4, is being tested in the MYSTIC, NEPTUNE, and PEARL phase 3 trials.

The POSEIDON trial is evaluating Imfinzi with and without tremelimumab in combination with chemotherapy.