Dive Brief:

• AstraZeneca and Daiichi Sankyo’s antibody drug Enhertu could become standard treatment for a large group of breast cancer patients following Phase 3 study results disclosed by the two companies on Monday.

• In a trial known as DESTINY-Breast04, Enhertu kept disease from spreading and extended survival longer than doctors’ choice of chemotherapy in patients with advanced breast cancer whose tumors express very little of the protein HER2. The partners didn’t disclose specifics, but said the benefits were observed regardless of which underlying form of disease patients had.

• The findings could position Enhertu to become the first treatment specifically meant for this group of breast cancer patients, who represent a majority of people diagnosed with the disease. They also add to a growing body of evidence that have helped validate the $7 billion gamble AstraZeneca made on the drug in 2019.

Dive Insight:

Over the past several years, AstraZeneca’s large bet on Enhertu has begun to pay off.

In late 2019, the drug was conditionally approved as a third-line treatment for the roughly 15% of breast cancer patients with HER2-positive disease. Enhertu has since succeeded in two additional late-stage breast cancer trials and could be cleared in the second-line setting by the middle of the year. Sales reached $214 million in 2021, more than double what they were in 2020. Analysts believe they’ll climb to more than $4 billion in 2026.

The summary study results AstraZeneca and Daiichi released on Monday are another important piece of evidence in support of the drug. Up to 55% of all breast cancer patients — including many with so-called HR-positive tumors, the most common form of the disease — have low levels of HER2 expression. That status makes them ineligible to receive the widely used HER2-targeting Roche cancer drugs Kadcyla, Herceptin and Perjeta, as well as other medicines from SeaGen and Macrogenics. Chemotherapy is the only treatment option for people with HR-positive tumors who have progressed after hormone therapy, and for people with HR-negative tumors.

The results “could potentially expand our ability to target the full spectrum of HER2 expression,” said AstraZeneca’s head of oncology R&D, Susan Galbraith, “validating the need to change the way we categorize and treat breast cancer.” Whether Enhertu lives up to that billing will depend on the magnitude of benefit, a detail that the companies plan to disclose at a future medical meeting.

In its statement, AstraZeneca reported a “clinically meaningful” improvement, compared to physician’s choice of chemotherapy, on both disease progression and survival. Whether Enhertu helps all patients with low HER2 levels or only those at the higher end of the spectrum will be important to determine its potential impact, noted Peter Welford, an analyst at Jefferies, in a note to clients. Shares could climb another three-plus percent if the drug works in all-comers, or fall if efficacy appears limited to certain patients, he wrote in a research note.

Another factor is the presence of interstitial lung disease, a type of lung scarring that is a known side effect of Enhertu and the focus of a Food and Drug Administration warning on its labeling. AstraZeneca said the rate of interstitial lung disease was consistent with what has been reported in other clinical trials, while the rate of death was lower. The actual numbers, however, will be important “given the stringent monitoring” required to detect and manage the side effect, Welford wrote.

Enhertu’s clinical trial successes have already impacted SeaGen, which earlier this month predicted flat or falling sales of its rival drug Tukysa because of emerging competition, mainly from Enhertu. SeaGen shares have slumped more than 15% since then, and both the biotech and Roche could face more pressure if Enhertu continues to perform well in additional trials.

Two other studies are expected to soon produce results. One is testing Enhertu in people with low HER2 in the second-line setting, with data anticipated in 2023, while the other is designed to confirm the drug’s benefits in third-line use for HER2-positive tumors.