Yesterday, the FDA approved Roche’s ado-trastuzumab emtansine (Kadcyla) for the adjuvant treatment of HER2-positive early breast cancer in patients who have residual invasive disease after neoadjuvant taxane- and trastuzumab-based therapy. The new indication could help to stave off some of the impact of biosimilar trastuzumab, which is expected to launch this year.
Yesterday, the FDA approved Roche’s ado-trastuzumab emtansine (Kadcyla) for the adjuvant treatment of HER2-positive early breast cancer in patients who have residual invasive disease after neoadjuvant taxane- and trastuzumab-based therapy.
The approval of the drug was based on the phase 3 KATHERINE study, a randomized, open-label trial in 1486 patients with HER2-positive EBC.1 Patients received either ado-trastuzumab emtansine or Roche’s trastuzumab (Herceptin), and the study’s primary end point was invasive disease-free survival. After a median follow-up of 40 months, the trial demonstrated a statistically significant improvement in the primary end point in patients who received ado-trastuzumab emtansine compared with those who received trastuzumab (hazard ratio for invasive disease or death, 0.50; 95% CI, 0.39-0.64; P <.0001), and safety data were consistent with the known profile of the study drug.
Ado-trastuzumab emtansine was first approved in the United States in 2013 for the treatment of HER2-positive metastatic breast cancer, and is a so-called “biobetter” of Roche’s older trastuzumab. The product is an antibody—drug conjugate (ADC), comprising the monoclonal antibody trastuzumab with maytansinoid DM1. Trastuzumab binds to HER2 on the tumor cell surface, and on internalization, the DM1 moiety inhibits cell division and the proliferation of cancer cells, providing a therapeutic advantage over trastuzumab alone.
Because there is no regulatory pathway specifically devised to address “biobetters,” and the term is typically used in marketing rather than in a scientific context, these products have the substantial business benefit of being treated as new agents. Altering an originator biologic will result in a therapy that must be addressed as a new product under existing regulatory pathways, and approval may lead to patent protection and market exclusivity that can help defend a company’s market share against biosimilar competition for originator products that have lost—or are about to lose—patent protection.2
Biosimilars of trastuzumab have already entered the European market and have begun to make an impact on Roche’s sales; Roche recently revealed that its sales for the innovator drug declined by 44% in the first quarter of this year. However, to date, the brand-name Herceptin, still top-selling drug for Roche, has no US biosimilar competition.
That is set to change, however, as 4 biosimilars (Ogivri, Herzuma, Ontruzant, and Trazimera) have been FDA approved, and Roche predicted in a 2018 earnings call that it would face its first biosimilar trastuzumab competition in the US market in the second half of 2019. Roche’s new indication for its biobetter could help to stave off some of the impact of those biosimilar launches, given the ADC’s advantages over trastuzumab.
1. von Minckwitz G, Huang CS, Mano MS, et al. Trastuzumab emtasine for residual invasive HER2-positive breast cancer. NEJM. 2019;380:617-628. doi: 10.1056/NEJMoa1814017.
2. Kesik-Brodacka M. Progress in biopharmaceutical development. Biotechnol Appl Biochem. 2018;65(3):306-322. doi: 10.1002/bab.1617.