LONDON, UK (GlobalData), 03 April 2012 - On March 30, 2012, Roche announced the preliminary success of its antibody-drug conjugate T-DM1 (trastuzumab emtansine) in a critical Phase III clinical trial. While the exact numbers are not yet available, Roche reports that top-line data from the EMILIA trial showed patients with HER2+ metastatic breast cancer that were treated with T-DM1 displayed a significant increase in progression free survival, as compared to those treated with lapatinib plus Xeloda.
T-DM1 is being developed under a licensing agreement between Roche’s Genentech and Immunogen, and is an exciting example of cutting-edge innovation in antibody-drug conjugate (ADC) development. Early ADCs (such as Seattle Genetics’ Adcetris) delivered chemotherapy directly to cancerous cells, by linking a small molecule chemotherapeutic to an antibody targeted towards a tumor specific marker. In contrast, Roche’s T-DM1 couples ImmunoGen’s cancer killer, DM1, to Genentech’s hugely successful therapeutic antibody Herceptin. In theory, T-DMI should provide the dual action benefits of Herceptin, which binds to the Human Epidermal Growth Factor Receptor 2 (HER2) expressed on the surface of some breast cancer cells. Herceptin binding to HER2 targets the cancer cells for destruction by the immune system, while simultaneously blocking growth-promoting HER2 signaling within the cell. By linking the anticancer compound DM1 to Herceptin, T-DM1 mounts a multi-pronged attack on breast cancer cells that express the HER2 receptor (HER2+ breast cancer). This is an important strategy in the fight against breast cancer, as it is a disease in which many cellular pathways upregulate to promote tumor cell survival when another pathway is targeted by a cancer drug. Breast cancer can be molecularly inhomogeneous between patients – therefore targeting a therapy towards a certain segment of patients (just as T-DM1 and Herceptin treat HER2+ breast cancer patients) encourages the likelihood of a drug’s success within a given population.
Roche, Immunogen and Genentech are all proudly touting T-DM1’s early success in the EMILIA trial. However, the improved overall progression free survival data presented is only one of the primary trial endpoints, and likely less important than improved overall survival (which requires more mature data). Genentech should be particularly sensitive to the fact that an improvement in progression free survival is not always enough to warrant drug approval. The UK’s National Institute of Health and Clinical Excellence never approved its blockbuster cancer drug Avastin for the breast cancer indication, and ultimately the FDA withdrew the drug from the US market due a lack of data showing improved overall survival and severe side effects that counteracted the small retardation of disease progression. Avastin was initially approved in the US in 2008 under the FDA’s accelerated approval program, and the FDA may have learned their lesson as they refused to file Genetech’s Biologics License Application for T-DM1 under the same accelerated approval program in 2010.
With this early data from the EMILIA trial, Genentech plans to try again and submit a Biologics License Application to the FDA for T-DM1 for treatment of metastatic HER2+ breast cancer later this year. Additionally, Roche plans to submit a Marketing Authorization Application to the European Medicines Agency. All parties involved seem to be optimistic; however, data demonstrating significant improvement in overall survival compared to current treatments for HER2+ metastatic breast cancer will be critical to the approval of T-DM1 by global regulatory and watchdog agencies. If they manage to fulfill this criterion, this collaboration stands to be extremely lucrative, as Herceptin sales amounted to 5.25 billion CHF in 2011. Following a recent epidemic of counterfeit Avastin in the US, and a loss of nearly 18% in Avastin sales attributed to the FDA’s withdrawal of its breast cancer indication, Roche and Genentech could really use a win.
* Roche’s T-DM1: Triple Threat To Breast Cancer or Another Avastin Disaster?
This expert insight was written by GlobalData’s oncology, hematology and infectious diseases analyst, Dr. Cheryl Strelko. If you would like an analyst comment or to arrange an interview, please contact us on the details below.
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