AstraZeneca and Daiichi's Enhertu winning streak rolls on with confirmatory trial victory in advanced breast cancer

AstraZeneca and its Japanese partner Daiichi Sankyo are likely sitting pretty on the heels of back-to-back approvals for cancer newcomer Enhertu. After a historic HER2-low green light at the beginning of the month—plus yet another approval last week—the blockbuster-to-be has clinched a confirmatory trial win. The latest data could see Enhertu strengthen its foothold in the breast cancer market, where Roche and Genentech’s Herceptin and Kadcyla have long reigned supreme.

In the late-stage Destiny-Breast02 trial, Enhertu alone trumped a physician’s choice between Roche’s Herceptin plus chemotherapy or Novartis' Tykerb plus chemotherapy at helping certain breast cancer patients live longer without their disease getting worse, the study's primary endpoint. The 600-patient trial also met its overall survival secondary endpoint, AZ and Daiichi said Monday.

The phase 3 study was conducted in about 600 patients with HER2-positive unresectable and/or metastatic breast cancer who had previously been treated with the antibody-drug conjugate Kadcyla, also known as trastuzumab emtansine.

Armed with data directly against Herceptin, the question will be whether Enhertu can jockey for space with Roche’s $2.91 billion breast cancer star. Enhertu is already competing directly with Kadcyla, which brought in about $2 billion for Roche last year.

“As this is the confirmatory trial for our current breast cancer indication in Europe and several other countries, we look forward to sharing these findings with regulatory authorities to add to the body of data for Enhertu for the treatment of HER2-positive metastatic breast cancer,” Ken Takeshita, M.D., global head of R&D at Daiichi Sankyo, said in a release.

AstraZeneca and Daiichi said they plan to present the new Enhertu data at an upcoming medical meeting. AZ and Daiichi’s phase 3 Breast02 study looked at a similar patient population as the single-arm Destiny-Breast01 phase 2 trial, which earned Enhertu its initial nod in 2019 for advanced HER2-positive metastatic breast cancer.

The drug’s safety profile was on par with that seen in previous phase 3 studies, with no new safety concerns identified, according to the partners. Further, rates of interstitial lung disease (ILD) matched up to those in other Enhertu trials in metastatic breast cancer, AZ and Daiichi said, noting that investigators flagged a “low rate of grade 5” ILD events.

Enhertu has been on fire this summer. After clinching a green light for second-line breast cancer use in May, the drug in early August inaugurated a new category of treatment with an approval as the first targeted therapy to treat unresectable or metastatic breast cancer expressing low levels of HER2, which was once part of the HER2-negative group.

Just a week after that, Enhertu bagged another August approval, this time scoring an accelerated nod in patients with HER2-mutant non-small cell lung cancer who’ve received a prior systemic therapy. The FDA OK makes AZ and Daiichi’s antibody-drug conjugate the first drug specifically approved for HER-2 mutant NSCLC, the FDA noted in a release.

Enhertu’s historic HER2-low approval, for its part, could unlock a massive sales opportunity for the med. According to data from the National Cancer Institute that the FDA cited, about 80% to 85% of 287,850 new breast cancer cases that will be diagnosed in the U.S. this year are considered HER2-negative by the old definition. Now, among them, about 60% fit the description of HER2-low.

With that massive patient pool in mind, Enhertu could reach $4.6 billion in sales in HER2-low patients by 2030, SVB Securities analyst Andrew Berens, M.D., previously projected.

Meanwhile, Daiichi notched a recent victory in court in its long-running Enhertu patent feud with Seagen. Last week, an arbitrator gave the win to Daiichi in the clash over an antibody-drug conjugate technology-sharing pact that stretches back to 2008.