Friday, April 5, 2013

Antibody-drug Combinations Delivering in Many Ways

Here's a nice review of the state of antibody-drug combinations (ADCs) as anticancer drugs, written by a team at Trinity Partners. Published in Nature Reviews Drug Discovery today, here's the highlight:
Genentech's ADC ado-trastuzumab emtansine was approved by the FDA in February 2013 following the positive outcome of the Phase III EMILIA trial. In this trial, patients with HER2-positive metastatic breast cancer had an improved median overall survival benefit compared to the combination of lapatinib and capecitabine. Genentech licensed ImmunoGen's Targeted Antibody Payload ADC technology — which includes their proprietary linker platform attached to DM1 — and combined it with the blockbuster HER2-specific monoclonal antibody trastuzumab. DM1 is a highly potent cytotoxic that is 100 to 10,000-times more potent than standard chemotherapies. As ADC technology enables selective targeting to tumour cells, ado-trastuzumab emtansine is highly effective and has less toxicity when used in this formulation compared to unconjugated DM1.
For what it's worth, DM1 is derived from other compounds that inhibit microtubule formation and thus cell division and is in the family of compounds like paclitaxel.  It's an agent that generally kills any cell it approaches, and based on it's potency I don't think it would make a useful chemotherapeutic on it's own.

Nevertheless, what makes the concept of antibody-drug combinations very appealing is the modularity of the approach:  You can focus on development of either the drug component or the targeting antibody.  Remember, the drug being delivered need not be the atomic bomb that is chemotherapy; and an antibody-drug payload technology still leaves space for development of disease specific drugs.  ADCs simply put them in the right place, and make for a nice neat ecosystem for researchers to operate within.