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Welcome Imfinzi: AstraZeneca crashes the checkpoint party late with a green light for durvalumab

And then there were 5.

The FDA handed out its latest approval for a PD-L1 checkpoint inhibitor on Monday afternoon, giving a green light to AstraZeneca to start selling durvalumab as Imfinzi as a second-line therapy for metastatic urothelial carcinoma.

Pascal Soriot

The regulatory OK comes in the wake of approvals for Merck, Bristol-Myers Squibb, Roche/Genentech and Pfizer/Merck KGaA. The biology of these new checkpoint drugs is well understood now, and the FDA issued its approval after a relatively small, single-arm study.

Regulators waved this one through after giving durvalumab a breakthrough drug designation and priority review, even though its the third approval for a checkpoint therapy in bladder cancer.

Durvalumab’s longterm success is crucial to the future of AstraZeneca and CEO Pascal Soriot. Billed as a blockbuster-to-be, following a commercial trail already clearly laid out, the big showdown for AstraZeneca comes later in the year, when it rolls out late-stage data on a combination of its checkpoint combo in its MYSTIC study, which matches durvalumab with tremelimumab, a CTLA-4 similar to Yervoy, for lung cancer.

The jury is still out, though, on how well a CTLA-4 drug — with all its attendant toxicity — will do in this field. That’s one reason why Bristol-Myers Squibb recently inked a deal with CytomX on a next-gen CTLA-4 that might prove far better for patients.

Seamus Fernandez at Leerink noted some modest expectations on this first approval. The upside lies further down the road.

Although this indication represents a relatively small opportunity for AZN (we forecast Imfinzi capturing 10% of our estimated ~$2.3B WW bladder cancer market), the approval will allow the agent to become more familiar with oncologists and should help facilitate future sBLAs for drug. The major indication for Imfinzi remains first-line (1L) non-small cell lung cancer (NSCLC) and we await top-line data from the Phase 3 MYSTIC trial in combination with tremelimumab (anti-CTLA-4) expected in mid-2017.

AstraZeneca, meanwhile, raised a red flag last week when it delayed its third-line readout in the ARCTIC study of the duo, spurring some suspicions that it was on track to a troubling failure that would have raised serious doubts about its future in the field.

The other question that many of us have is how many of these PD-1/PD-L1 checkpoints can be approved before they start slicing and dicing this market into ever smaller bites. A range of second-wave checkpoints are in development now, with everyone that’s financed well enough and interested in it going after one of their own.

That group includes Incyte, which has been partnering with the mainstream checkpoints in nonexclusive arrangements. And the main players, like Merck and Bristol-Myers, are already well along with their own combination trials. Hundreds of them.

The approval, though, marks a big win for AstraZeneca, which has made significant progress on the oncology front in the last few years. They had to have this one to remain a credible rival. And they got it.

The FDA has been on a drug approval spree over the last few days. This is the fifth OK for a new chemical entity in the last three working days, bringing the year-to-date total to 19. Last year, which saw a big dip in approvals, the FDA approved a total of 22 new drugs.


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RAPS Regulatory Convergence 2017