Cambridge Healthtech Institute’s Kent Simmons recently spoke with Dr. Janice Reichert, Executive Director of The Antibody Society, about her upcoming Keynote presentation “Trends and Challenges in the Development of Therapeutic Antibodies for Non-Oncology Indications”, to be delivered at the Emerging Indications for Therapeutic Antibodies meeting at PEGS Boston 2018.
The number of first approvals for antibody therapeutics has increased recently. Are many of these products for non-cancer indications?
The increase in first approvals in the US or European Union, which are typically key markets for antibody therapeutics, has been amazing. Despite the fact that the first antibody therapeutic was approved over 30 years ago, 45% of all first approvals for innovative antibody therapeutics were granted during 2014-2017. Although the products for cancer garner substantial attention, those for non-cancer indications comprised the majority of approvals (17 of 31 (55%) products) during the past 4 years. Notable recent first approvals include emicizumab (Hemlibra®), a bispecific antibody for hemophilia A, and ocrelizumab (Ocrevus®), an anti-CD20 antibody for relapsing forms of multiple sclerosis and primary progressive multiple sclerosis. As a reference, The Antibody Society maintains a list of antibody therapeutics granted approvals in the US or European Union, which currently includes 69 products, on their website.
What is in the clinical pipeline?
Antibody therapeutics for non-cancer indications are designed to prevent or treat a wide variety of diseases, including migraines, HIV infection, and sickle cell disease, as well as many immune-meditated disorders such as lupus. Overall, these therapeutics comprise 42% of the ~580 commercially sponsored antibody therapeutics currently in clinical studies. Most are canonical, full-length molecules that may have undergone engineering to enhance functionality. The more dramatically modified molecules include bispecific antibodies and immunoconjugates. Mixtures of antibodies are also being evaluated for non-cancer indications, primarily infectious diseases. Interestingly, antibody therapeutics for non-cancer indications are not evenly distributed among the three phases of clinical development. They currently comprise ~30% of those in Phase 1 studies, but ~50% of those that advanced to Phase 2 or Phase 3.
What are the success rates for non-cancer vs cancer indications?
The antibodies for non-cancer indications tend to have higher clinical phase transition rates and overall approval success rates. The Antibody Society recently calculated success rates for commercially sponsored antibody therapeutics that entered clinical study during the 2000-2009 and during 2005-2014. For those that entered clinical study during the 2000s, the overall rates for approval in the US or European Union were 24% and 20% for antibody therapeutics for non-cancer and cancer indications, respectively. Regarding the phase transitions, the largest difference was seen in the Phase 1 to 2 transition rates, which were 82% and 69% for antibody therapeutics for non-cancer and cancer indications, respectively. For all antibodies that entered clinical study during 2005-14, the Phase 1 to 2 transition rates were similar to those of the older molecules, which is reassuring given the larger number of non-canonical (e.g., antibody-drug conjugates, bispecific antibodies) that have entered clinical study recently. Other transition rates were slightly higher, but it should be noted that relatively few molecules in this group had advanced to late-stage clinical studies or beyond.
What is the diversity among targets for antibodies in the pipeline?
Given the diversity of indications, the substantial diversity of the targets for antibodies for non-cancer indications is not surprising. With over 240 antibodies in studies of non-cancer indications, only ~20 antigens are the targets of 3 or more of these antibodies. The antigens include amyloid, tau, complement 5, CD28, CD40, IL-6, IL-13, IL-17, IL-33, GM-CSF, HIV and influenza virus. There are thus many medically relevant antigens that are the targets of only one antibody in the clinic, which suggests that the clinical pipeline could easily be expanded. The study of more antibodies per target would increase the possibility that one (or more) might be approved in the future.
And finally, could you please give us an update on the activities of The Antibody Society?
The Society has a variety of ongoing initiatives. For example, we are engaging in substantive discussions with the World Health Organization’s International Non-proprietary Names (INNs) Expert Group regarding the definitions used to assign INNs. Prof. Andreas Plückthun has been appointed biological and publications advisor to the Expert Group and will be the Society’s representative at their upcoming meetings. In late 2017, we added the Adaptive Immune Receptor Repertoire (AIRR) Community as a section of the Society. The AIRR Community is developing recommendations for: 1) a common repository for AIRR sequence data, 2) standards for publishing and depositing AIRR sequence data, and 3) resources and guidelines for the evaluation of molecular and statistical methods for AIRR sequence data. Finally, the success rates that I mentioned were derived from data collected for our ongoing study of metrics for antibody therapeutics development. As part of this study, the Society is maintaining a carefully curated dataset of publically available information about molecular characteristics (e.g., format, target(s), isotype), development stage and indications studied for antibody therapeutics in the commercial clinical pipeline. Such comprehensive data is difficult to find in commercially available databases.
Speaker Biography:
Janice M. Reichert, Ph.D., Executive Director, The Antibody Society
Dr. Janice Reichert is an internationally-recognized expert in the development of antibody therapeutics. She is Executive Director of The Antibody Society, a non-profit association representing individuals and organizations that engage in antibody research or development. Dr. Reichert is also Founder and Editor-in-Chief of mAbs, a peer-reviewed, PubMed-indexed biomedical journal that focuses on topics relevant to antibody research and development, and Founder and Managing Director of Reichert Biotechnology Consulting LLC, a pharmaceutical business intelligence research firm. Dr. Reichert writes frequently on development trends for antibody therapeutics, including the annual ‘Antibodies to watch’ articles published in mAbs, and she has presented her research results as an invited speaker at conferences held worldwide.