Since the approval of the first antibody-drug conjugate or ADC, now more than 15 years ago, scientists and researchers have sent more than 50 ADCs to be clinically evaluated in ongoing clinical research programs. While some of the trial results have indeed been impressive, some of the results have been mixed. At a time when some may worry about a high rate of attrition, researchers have correctly pointed out that a high rate of attrition in phase I and II means that only the best trial drugs advance to phase III trials and beyond.
In reviewing the cause of failure of antibody-drug conjugates in clinical trials, researchers are looking at a great number of reasons, including the possibility of linker instability as one possible aspect causing systemic toxicity. But they are also asking if failure may be caused by safety concerns with maximum tolerable dose and low therapeutic index. Why does preclinical data not translate to clinical efficacy in human? Are these problems caused by an insufficient understanding of antibody-drug conjugate metabolism in vivo?
In October 2015, during CPhI World Wide in Madrid, Spain we asked experts from Piramal Pharma Solutions, Carbogen Amcis and Catalent about challenges in the manufacturing of ADCs and how they see the market for ADCs evolve.