Enhertu’s market conquest continues apace. Daiichi Sankyo and AstraZeneca’s star antibody-drug conjugate, which already has annual sales of $5 billion, has secured FDA approval as a treatment for early-stage breast cancer, further encroaching on the territory of Roche’s Kadcyla.
The FDA has simultaneously given Enhertu the go-ahead for both neoadjuvant and postoperative therapy in patients with HER2-positive early-stage breast cancer, the companies announced Friday. The FDA originally aimed to make a decision by July 7, so the adjuvant treatment agreement came nearly two months ahead of schedule.
Although early, there are pitfalls with adjuvant labels. Patients who receive Enhertz preoperatively will not be able to continue on a HER2-directed ADC in the postoperative setting.
Specifically, in adjuvant therapy, Enhertz is currently approved for patients with HER2-positive breast cancer who have residual invasive disease after treatment with trastuzumab (Herceptin) (with or without Roche’s Perjeta) and taxane-based therapy. When announcing the FDA’s priority review in March, Daiichi Pharmaceutical and the state of Arizona explained that the indication would be “after preoperative HER2-targeted therapy,” and if approved, it would also cover previous use of Enhertz. But apparently the broader label didn’t work out.
In the neoadjuvant setting, Enherz is approved in addition to THP regimens (taxanes, Herceptin, Perjeta) for the treatment of HER2-positive stage 2 or stage 3 adult breast cancer.
Despite labeling limitations, some physicians may use Enhertu in an adjuvant setting after neoadjuvant Enhertu.
Enherz’s indication for adjuvant early breast cancer treatment is supported by data from the Destiny-Breast05 trial showing that the drug reduced the risk of invasive disease recurrence or death by 53% compared to Kadcyla.
In the neoadjuvant setting, the Destiny-Breast11 study found a pathological complete response (pCR) rate of 67.3% for enhertz followed by THP, which was significantly higher than 56.3% for high-dose doxorubicin and cilophosphamide followed by THP. pCR means no residual disease is found in the resected tissue.
In an interview with Fiers at the European Society of Clinical Oncology annual meeting in October, Daiichi and Arizona executives suggested that doctors would be less hesitant about re-treating patients with residual disease because neoadjuvant therapy includes only four cycles of Enhertz.
“I don’t think that even if you’ve had just four cycles of Enhertz treatment and had a very good response, that doesn’t necessarily mean you’re resistant to Enhertz again in that setting,” Dr. Susan Galbraith, Arizona State’s director of oncology research and development, said at the time.
In a separate interview on the sidelines of the JPMorgan Healthcare Conference in January, Ken Keller, head of Daiichi’s global oncology business, acknowledged that doctors are divided on whether reusing Enhertz is appropriate, but suggested that “the vast majority” agree with the proposed approach because Enhertz is the most potent HER2 drug to date.
However, reimbursement for continued use may be difficult due to the adjuvant label excluding previous use of Enhertz and the fact that the Destiny-Breast05 study did not enroll patients who received ADCs as neoadjuvant therapy.
In any case, Enherz’s latest expansion is expected to have a lot to do with Kadcyla, which is counting heavily on the use of adjuvants for its remaining growth in the U.S. after losing out to Enherz in metastatic disease.
Since its initial FDA approval for previously treated metastatic breast cancer in late 2019, Enhertu has transformed the standard of care in HER2-positive breast cancer. It wasn’t until December that the FDA approved the combination of Enherz and Perjeta as a first-line treatment.
Enhertu has moved up the treatment order and established HER2-low as a new therapeutic area, resulting in increased sales. The combined sales recorded by AZ and Daiichi surged by 31% in the first quarter of 2026, reaching $1.4 billion. First, Enhertz’s global sales are projected to be 861.3 billion yen ($5.4 billion) for fiscal year 2026, which ends in March 2027.
Enhertz is a key pillar of Daiichi’s newly announced five-year plan to increase sales to more than 3 trillion yen by fiscal 2030. The company also aims to become a top-five global oncology company by 2035, by which time Enherz will no longer have patient protections.
