Chugai Pharmaceutical Co., Ltd. has filed a new drug application to the Ministry of Health, Labour and Welfare (MHLW), for antibody-drug conjugate “trastuzumab emtansine (T-DM1)” for the treatment of “HER2-positive metastatic or recurrent breast cancer.”

Chugai filed the application with the MHLW based on the results from an overseas phase III clinical trial (the EMILIA trial) and a domestic phase II clinical trial.

The EMILIA trial is an international phase III study comparing T-DM1 alone to lapatinib in combination with capecitabine in people with HER2-positive metastatic or unresectable locally advanced breast cancer who had previously been treated with trastuzumab and a taxane chemotherapy.  Japanese patients were not included in the EMILIA trial.

The EMILIA trial had progression free survival (PFS) as one of its primary endpoints, and patients who received T-DM1 experienced a 35 per cent reduction in the risk of their disease worsening or death compared to those who received lapatinib plus capecitabine. The median PFS improved by 3.2 months from 6.4 months of lapatinib and capecitabine to 9.6 months of T-DM1 (hazard ratio=0.65; p<0.0001).

As for overall survival (OS), another primary endpoint, the results showed the risk of death was reduced by 32 per cent for patients who received T-DM1 compared to those who received lapatinib plus capecitabine. Patients in the study treated with T-DM1 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, fewer patients who received T-DM1 experienced Grade 3 or higher AEs than those who received lapatinib plus capecitabine. The most common Grade 3 or higher AEs reported in patients receiving T-DM1, 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 T-DM1 in Japanese patients.

The number of patients newly diagnosed with breast cancer in Japan continues to rise each year and is estimated at approximately 60,000 annual average in 2015-2019. And HER2 expression has been observed in approximately 20 per cent of breast cancer patients.

As the top pharmaceutical company in the field of oncology, Chugai will work for the approval to provide patients and medical professionals with new treatment options as soon as possible.

T-DM1 is comprised of the antibody trastuzumab and the chemotherapy DM1 attached together using a stable linker. T-DM1 is designed to target HER2, inhibit HER2 signalling, induce antibody-dependent cell mediated cytotoxicity, and deliver the chemotherapy DM1 directly inside HER2-positive cancer cells. Once trastuzumab emtansine is taken up by those cancer cells, it is designed to destroy them by releasing the DM1.

A Biologics License Application (BLA) for T-DM1 for people with previously treated, HER2-positive breast cancer has been submitted to the US Food and Drug Administration (FDA) by Genentech and a Marketing Authorisation Application has been submitted to the European Medicines Agency (EMA) by Roche. FDA granted priority review for the BLA for T-DM1, with an expected action date of February 26, 2013.

Trastuzumab (Herceptin) is a personalized medicine, developed by Roche, which targets and blocks the function of HER2.