Dawn of A New Era: Antibody-drug Conjugates in the Treatment of Cancer

Two decades ago, antibody-drug conjugates or ADCs were hailed as a major breakthrough, especially in the area of oncology therapeutics.

The concept of delivering a potent drug payload directly to the site of the tumor for maximum effect with minimal damage caused to non-cancerous cells was viewed as, if not the Holy Grail of cancer treatment, at least a significant advance towards precision medicine.

The concept has, however, proved difficult to translate into clinical success.

The first ADC reached the market in 2000, but to date, the United States Food and drug Administration (FDA) has approved only four ADC therapeutics.

The two most recent were granted approval in 2017, and could mark the start of a new era in which ADCs begin to realize their full potential.

Drug approval
The two drugs approved most recently by the FDA are inotuzumab ozogamicin (Besponsa?; Pfizer) and gemtuzumab ozogamicin (Mylotarg?; Pfizer). Mylotarg, the very first marketed ADC, was originally approved in 2000 for treatment of CD33-positive acute myeloid leukemia (AML).

However, treatment-related toxicity concerns led to its withdrawal from the market in 2010, but it has now been re-approved with a lower recommended dose and altered dosing schedule.

Besponsa was approved for treatment of relapsed/refractory acute lymphoblastic leukemia (ALL).[1,2] They join brentuximab vedotin (Adcetris?; Seattle Genetics), an anti-CD30 monomethyl auristatin E (MMAE) conjugate approved in 2011 to treat relapsed/refractory Hodgkin lymphoma and systemic anaplastic large cell lymphoma, and ado-trastuzumab emtansine (Kadcyla?; Genentech/Roche), an anti-HER2 DM1 conjugate approved in 2013 to treat HER2+ metastatic breast cancer. Kadcyla is currently the only FDA-approved ADC for the treatment of solid tumors.

In the first of a two-part article published in ADC Review | Journal of Antibody-drug Conjugates, David Rabuka, Ph.D (Catalent Pharma Solutions) and Penelope Drake, Ph.D (Catalent Pharma Solutions) review the development of Antibody-drug Conjugates.

[Click here] to read the full article.


Last Editorial Review: August 29, 2018

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