AstraZeneca and Daiichi Sankyo have been granted conditional approval in the European Union (EU) as a monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens.
The approval by the European Commission was based on positive results from the single-arm DESTINY-Breast01 Phase II trial, in which Enhertu showed clinically meaningful and durable antitumour activity in patients with HER2-positive metastatic breast cancer who had received two or more prior anti-HER2-based regimens. It follows the December 2020 recommendation for approval by the Committee for Medicinal Products for Human Use of the European Medicines Agency, which reviewed the application under its accelerated assessment procedure.
In the DESTINY-Breast01 Phase II trial, after a median follow-up of 20.5 months, Enhertu showed a confirmed objective response rate (ORR) of 61.4%, including a 6.5% complete response rate and a 54.9% partial response rate, and an estimated median duration of response (DoR) of 20.8 months for patients with HER2-positive metastatic breast cancer who had received at least two previous lines of therapy.
The safety of Enhertu has been evaluated in a pooled analysis of 234 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of Enhertu 5.4mg/kg in clinical trials. The most common adverse reactions were nausea, fatigue, vomiting, alopecia, constipation, decreased appetite, anaemia, neutropenia, diarrhoea, thrombocytopenia, cough, leukopenia and headache. Cases of interstitial lung disease (ILD) or pneumonitis, were reported in 15.0% of patients, and in 2.6% of patients, ILD led to death.
Enhertu (5.4mg/kg) is approved in the US under accelerated approval, and in Japan under the conditional early approval system for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting based on the DESTINY-Breast01 Phase II trial. It is also approved in the US and Japan for the treatment of patients with HER2-positive unresectable advanced or recurrent gastric cancer that has progressed after a trastuzumab-containing regimen based on the DESTINY-Gastric01 Phase II trial.
Enhertu is being further assessed in several ongoing Phase III breast cancer trials as part of a broad development programme, including DESTINY-Breast02, a confirmatory trial in 3rd-line HER2-positive metastatic breast cancer, and DESTINY-Breast03, as a 2nd-line treatment. DESTINY-Breast04 is testing Enhertu in patients with metastatic breast cancer and low expression of HER2; and DESTINY-Breast05 is evaluating Enhertu as an adjuvant treatment of patients with high-risk HER2-positive early breast cancer. Additional ongoing trials are testing Enhertu in combination with other anti-cancer medicines in HER2-positive and HER2-low metastatic breast cancer.
Following EU approval, an amount of $75m is due from AstraZeneca to Daiichi Sankyo as a milestone payment for HER2-positive breast cancer. In AstraZeneca, the milestones paid will be capitalised as an addition to the upfront payment made in 2019 and subsequent capitalised milestones and amortised through the profit and loss.
Sales of Enhertu in most EU territories are recognised by Daiichi Sankyo. AstraZeneca reports its share of gross profit margin from Enhertusales in those territories as collaboration revenue in the Company’s financial statements. AstraZeneca will record product sales in respect of sales made in territories where AstraZeneca is the selling party.
Photo: AstraZeneca R&D