EMA Validates and Grants Accelerated Assessment for Trastuzumab Deruxtecan (Enhertu) in HER2-Positive Metastatic Breast Cancer with 60.3% Overall Response Rate

July 07, 2020 /BioValleyBIOON/ -- Daiichi Sankyo recently announced that the European Medicines Agency (EMA) has acceptedBreast CancerMarketing Authorization Application (MAA) for the new drug Enhertu (fam-trastuzumab deruxtecan, DS-8201), a HER2-targeted antibody-drug conjugate (ADC), for the treatment of patients with unresectable or metastatic HER2-positive breast cancer who have previously received at least two anti-HER2 therapeutic regimens. The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has granted accelerated assessment to Enhertu and initiated scientific review. The CHMP typically evaluates products expected to be of major public health interest and therapeutic innovation, which significantly shortens the evaluation timeline.

Enhertu is co-developed by Daiichi Sankyo andAstraZeneca(AstraZeneca) collaboration for global development, with Daiichi-Sankyo retaining exclusive rights in the Japanese market. In the United States and Japan, Enhertu has been approved for adult patients with unresectable or metastatic HER2-positive breast cancer who have previously received at least two HER2-directed regimens. The approval was based on the pivotal Phase II DESTINY-Breast01 trialTumorObjective response rate (ORR=60.3%) and duration of response (median DOR=14.8 months) data. Further approval will depend on the verification and characterization of clinical benefit in confirmatory trials. It should be noted that the drug label for Enhertu contains a boxed warning regarding interstitial lung disease (ILD)/pneumonitis and embryo-fetal toxicity.

Daiichi SankyoTumorDr. Gilles Gallant, Global Head of R&D, stated: “The EU’s accelerated assessment underscores the significant unmet medical need among patients with HER2-positive metastatic breast cancer, a need that Enhertu has the potential to address. The drug is already in use among patients in the United States and Japan, and we look forward to collaborating with the EMA to bring this important new medicine to patients in the EU as soon as possible.”

DESTINY-Breast01 is a pivotal, single-arm, open-label, global, multicenter, two-part trial evaluating the safety and efficacy of Enhertu (5.4 mg/kg) as monotherapy in patients with HER2-positive unresectable and/or metastatic breast cancer. The study enrolled 184 patients from more than 100 clinical sites worldwide. These patients had previously received two or more HER2-targeted regimens; the median number of prior therapies for metastatic disease was 6 (range: 2–27). Prior therapies included trastuzumab emtansine (T-DM1; 100% of patients), trastuzumab (100%), pertuzumab (65.8%), other anti-HER2 therapies (54.3%), hormonal therapy (48.9%), and other systemic treatments (99.5%). The primary endpoint was the overall response rate (ORR), as assessed by an independent central review committee (IRC). In the study, the median duration of treatment with Enhertu was 10 months (range: 0.7–20.5), and the median follow-up time was 11.1 months (range: 0.7–19.9). As of the data cutoff date of August 1, 2019, 42.9% of patients were still receiving treatment.

The study results were published in the New England Journal of Medicine (NEJM). The data showed that the objective response rate (ORR) for Enhertu monotherapy (5.4 mg/kg) was 60.3% (n=111; 95% CI: 52.9–67.4), with a complete response (CR) rate of 4.3% (n=8) and a partial response (PR) rate of 56.0%. The disease control rate (DCR) was 97.3%, the median duration of response (DoR) was 14.8 months (95% CI: 13.8–16.9), and the median progression-free survival (PFS) was 16.4 months (95% CI: 12.7–not estimable). The median overall survival (OS) was not reached, with an estimated one-year survival rate of 86%. Results were consistent across all subgroups. The safety and tolerability profile of DS-8201 in this study was consistent with that observed in Phase I trials.

Approximately 20% of breast cancer cases are HER2-positive. Despite therapeutic advances in recent years and the approval of several new drugs, there remains a significant unmet clinical need among patients with HER2-positive metastatic breast cancer. This disease remains incurable, and patients ultimately experience disease progression after receiving currently available therapies. HER2 is a growth-promoting protein and tyrosine kinase receptor expressed in variousTumorCell surface expression, including in gastric cancer, breast cancer, and lung cancer, is associated with aggressive disease and poorer prognosis.

Enhertu is a next-generation antibody-drug conjugate (ADC) that links trastuzumab, a humanized monoclonal antibody targeting HER2, to an exatecan derivative (DX-8951 derivative, DXd), a novel topoisomerase I inhibitor, via a tetrapeptide linker. This enables targeted delivery of the cytotoxic agent into cancer cells, thereby reducing systemic exposure to the cytotoxic agent compared with conventional chemotherapy.

In March 2019, AstraZeneca and Daiichi Sankyo reached an agreement worth a total of $6.9 billion for immunologyTumoracademic collaboration to jointly develop Enhertu for treating cancer patients with various levels of HER2 expression or HER2 mutations, including gastric cancer, colorectal cancer, lung cancer, and HER2-low breast cancer. The pharmaceutical market research firm EvaluatePharma previously predicted that Enhertu’s sales would reach $2 billion in 2024. (Bioon.com)

Original Source:EMA Validates and Grants Accelerated Assessment for Trastuzumab Deruxtecan for the Treatment of HER2 Positive Metastatic Breast Cancer