Chugai Pharmaceutical Co., Ltd. has received approval from the Japanese Ministry of Health, Labour and Welfare (MHLW) for “HER2-positive inoperable or recurrent breast cancer,” for the HER2 targeted anti-body drug conjugate, “Kadcyla Intravenous Infusion 100 mg and 160 mg” (generic- trastuzumab emtansine).

In January 2013, Chugai filed a new drug application for approval for HER2-positive inoperable or recurrent breast cancer based on results from a Japanese phase II clinical trial and a global phase III clinical trial (The EMILIA trial). This approval was obtained based on data from these clinical trials.

The EMILIA trial is an international phase III study comparing Kadcyla alone to lapatinib in combination with capecitabine in patients with HER2-positive metastatic or unresectable locally advanced breast cancer who had previously been treated with trastuzumab (Herceptin) and a taxane. Patients from Japan were not included in this trial.

Progression free survival (PFS) was one of its primary endpoints, and patients who received Kadcyla experienced a 35 per cent reduction in the risk of disease progression or death compared to those who received lapatinib plus capecitabine. The median PFS improved by 3.2 months from 6.4 months on lapatinib and capecitabine to 9.6 months on Kadcyla (hazard ratio=0.65; p<0.0001).

As for overall survival (OS), another primary endpoint, the risk of death was reduced by 32% for patients who received Kadcyla compared to those who received lapatinib plus capecitabine. Patients in the study treated with Kadcyla survived a median time of 5.8 months longer than those who received lapatinib and capecitabine (median OS: 30.9 months vs. 25.1 months) (hazard ratio=0.68; p=0.0006).

Regarding safety, 40.8 per cent of the patients who received Kadcyla and 57.0 percent of the patients who received lapatinib plus capecitabine experienced Grade 3 or higher AEs. The most common Grade 3 or higher AEs reported in patients receiving Kadcyla, compared to those receiving lapatinib plus capecitabine, included low platelet count and increase of AST and ALT levels.

The phase II trial conducted in Japan confirmed the efficacy and the tolerability of Kadcyla in Japanese patients with HER2-positive metastatic or unresectable locally advanced breast cancer.
The number of patients newly diagnosed with breast cancer in Japan has been continuing to rise each year and is estimated to become approximately 60,000 during 2015-2019 on annual average. Overexpression of HER2 has been observed in approximately 20 per cent of breast cancer patients.

As the top pharmaceutical company in the field of oncology, Chugai is convinced that Kadcyla can contribute to the treatment of patients with “HER2-positive inoperable or recurrent breast cancer” by providing a new therapeutic option.

Kadcyla is an anti-body drug conjugate. It comprises of the anit-HER2 humanized monoclonal antibody, trastuzumab, and a chemotherapeutic drug, DM1, attached together using a stable linker. Kadcyla is designed to target HER2, inhibit HER2 signaling, induce antibody-dependent cell mediated cytotoxicity, and deliver the chemotherapeutic drug DM1 directly inside HER2-positive cancer cells. Once Kadcyla is taken up by those cancer cells, it is designed to destroy them by the DM1.

Kadcyla was approved for patients with previously treated, HER2-positive metastatic breast cancer in the US in February 2013 and a Marketing Authorisation Application has been submitted to the European Medicines Agency (EMA) by Roche.

Roche licenses technology for Kadcyla under an agreement with ImmunoGen, Inc.