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Dive Brief:

• An AstraZeneca and Daiichi Sankyo medicine didn’t significantly extend survival in people with non-small cell lung cancer who were expected to benefit most from treatment, raising questions about whether U.S. regulators may approve the drug later this year.

• Data presented at the World Conference on Lung Cancer Monday showed people with the nonsquamous form of non-small cell lung cancer and treated with datopotamab deruxtecan lived a median of 2.3 months longer than those who received chemotherapy in a Phase 3 trial. The findings represent a “clinically meaningful trend” towards improved survival, but didn’t meet statistical significance, AstraZeneca said.

• The Food and Drug Administration will decide by Dec. 20 whether to approve datopotamab deruxtecan as a second-line treatment for people with nonsquamous, non-small cell lung cancer. The new survival findings “make us suspicious about a straight approval,” wrote Stifel analyst Eric Le Berrigaud in a Tuesday note to investors. A delayed decision and an advisory committee meeting appear to be “reasonable assumptions,” he added.

Dive Insight:

Datopotamab deruxtecan, or dato-dxd for short, is the product of a collaboration between AstraZeneca and Daiichi to develop precision cancer drugs known as antibody-drug conjugates.

The partners believe ADCs can supplant chemotherapy in many tumor types. Their drug Enhertu, a fast-selling medicine that’s changed how certain breast cancers are treated, is a prime example. But unlike Enhertu, which was first approved in 2019 and has since succeeded in a variety of different trials, dato-dxd’s case to regulators is less straightforward.

AstraZeneca and Daiichi had hoped to bring the drug to market for all people whose non-small cell lung tumors express a protein, TROP2, that it’s designed to target. That population would be a large market, as TROP2 is overexpressed in most types of lung tumors.

Yet expectations have since been dialed back. Dato-dxd delayed tumor progression in a Phase 3 trial testing it against the chemotherapy docetaxel in people who had received at least one prior therapy. But it didn’t significantly extend survival in the overall study population. Some people who received dato-dxd and didn’t respond had a “detrimental effect” compared to docetaxel, suggesting they should be excluded from future testing and shouldn’t receive it in a commercial setting, wrote Stifel’s Le Berrigaud on Tuesday.

AstraZeneca and Daiichi have focused on the drug’s seeming benefit for people whose tumors are classified as nonsquamous, a group they believe could better benefit from treatment. They submitted an approval application for use in these patients specifically, and the Food and Drug Administration in February agreed to review it.

Study results revealed at WCLC, though, “add a layer of complexity” to the companies’ argument, according to Le Berrigaud. The difference in median survival between the 14.6 months reported for the nonsquamous group and the 12.3 months for people given docetaxel wasn’t statistically significant, which “may be weighed by the FDA” during its review, wrote Leerink Partners analyst Andrew Berens in a separate note.

Efforts to better identify responders have also been complicated. AstraZeneca and Daiichi have been working with Roche on a diagnostic to measure levels of TROP2, and on Monday presented results from an after-the-fact analysis suggesting treatment benefits for people with so-called actionable genomic alterations. The latter group could help the companies secure an approval, albeit in a “limited population,” Berens wrote.

“There is an unequivocal benefit with dato-dxd for some patients, and at a reasonable price in terms of toxicity, but the exact target population and how it should be addressed are complex topics,” Le Berrigaud added.

AstraZeneca shares fell by as much as 5% during Tuesday trading on the London stock exchange.