September 24,2013 | By Márcio Barra
Kadcyla (ado-trastuzumab emtansine, or T-DM1), from Roche/Genentech, was approved on the September 2013 meeting of the EMA’s Committee for Medicinal Products for Human Use. This is the drug’s third approval in a major territory, following the US FDA’s approval back in February and in Japan for the treatment of HER2+ positive inoperable or recurrent breast cancer.
Kadcyla is a therapy for patients with HER2-positive, late-stage (metastatic) breast cancer, consisting of the antibody trastuzumab, connected to a drug called DM1, from ImmunoGen. The medicine, which comes in two dosage forms, 100 mg and 160 mg, was approved for the treatment of adult patients with HER2-positive, unresectable locally advanced or metastatic breast cancer who previously received trastuzumab and chemotherapy, separately or in combination.
HER2 is a protein encoded by ERBB2, a proto-oncogene located in chromosome 17. Over-expression of this proto-oncogene occurs in roughly 30% of breast cancers, and the increased amount of HER2 protein contributes to the breast cancer cell growth and survival.
Kadcyla’s mechanism of action is a new spin on trastuzumab therapy. In Kadcyla, the antibody, trastuzumab, is linked to the chemotherapy agent, DM1 (or mertansine) through a stable linker. The antibody essentially delivers the chemotherapy agent directly to the cell growth protein HER2.
As it was designed for late-stage breast cancer, this drug is only intended for HER-2 positive patients that have not responded to trastuzumab or chemotherapy. Data from a phase III trial, EMILIA, shows that patients survived a median of 30.9 months, as opposed to 25.1 months with the alternative treatment, lapatinib plus capecitabine, alongside an increased progression free survival (9.6 months versus 6.4 months). Common side effects observed during clinical trials include haemorrhage, increased transaminases (liver enzymes), fatigue, musculoskeletal pain, and headache.
Alongside Herceptin and Perjeta (the latter approved in March in Europe), Kadcyla further reinforces Roche’s position in the breast cancer market. Herceptin will face patent expiration in 2014 and 2019 for Europe and US, respectively, and biosimilar competition is expected from Amgen, Pfizer and Novartis against Roche’s cancer drug. Kadcyla is thus expected to replace revenue lost from Herceptin’s patent ending.