Potent New Weapons in the Oncology Arsenal (Antibody-Drug Conjugates) Require Unique Biological Manufacturing Expertise

Abstract

Recent advances in coupling antibodies to potent cytotoxic drugs have resulted in stable delivery platforms with improved pharmacokinetics which spares patients from the debilitating systemic toxicity observed with traditional chemotherapy [1]. In 2011 the FDA granted accelerated approval to Seattle Genetics Adcetris® (Bentuximab vedotin) and on Feb. 4th 2013 Health Canada approved the drug which uses a chimeric monoclonal antibody to target CD-30 positive cells. The cytotoxic warhead conjugated to the antibody consists of the potent antimitotic agent monomethyl auristatin E. This is the first new therapy approved since 1977 for treatment of Hodgkin’s lymphoma and it is the first therapy to receive approval against anaplastic large cell lymphoma. Roche-Genentech received approval to offer Kadcyla® (Trastuzumab emtansine) for the treatment of patients with HER2-positive metastatic breast cancer in Feb. 2013. Results from the pivotal EMILIA trial demonstrated significantly improved overall survival compared to current standard of care which uses capecitabine and lapatinib. Kadcyla is the Herceptin antibody conjugated to the maytansine derivative DM1. Manufacturing these highly potent biopharmaceuticals presents a series of unique engineering and chemistry challenges which has resulted in several contract manufacturers constructing facilities to address the unique engineering and chemistry challenges associated with this promising class of therapeutic drugs. By leveraging experience in biopharmaceuticals and potent small molecule drug process development this class of promising new therapies can be reliably and safely manufactured to meet clinical and commercial demands. This article will investigate the experience of Lonza as it synergistically pooled internal resources to address this promising class of therapeutics. Keywords: ADC facilities, ADC linkers, ADC manufacturing, antibody-drug conjugates, cytotoxins.