by: Dawn M. Ecker
Antibody related products have been a staple in the biopharmaceutical landscape for over 10 years. In preparing a chapter for a soon to be published road map for developing therapeutic monoclonal antibody products, the reality became clear that antibody related products are the cornerstone of the biopharmaceutical market. Representing over a third (35%) of all approved and currently marketed recombinant products (73 of 208), antibody products generated just over $89B of the $154B in sales of biopharmaceuticals for 2015.
Since recombinant products entered the market in 1982, 88 antibody related products have been approved over the last 34 years. If we take a closer look at the number of antibody related products approved every year, since the approval the first therapeutic monoclonal antibody Orthoclone OKT3 in 1986, the number of antibody products have steadily increased over the last few years with 2016 recording an unprecedented approval of 11 antibody products by the FDA and the EMA (see Figure 1 below). Of the 2016 approved products, seven are full length monoclonal antibodies: Anthim, Cinqair/Cinqaero, Lartruvo, Taltz, Tecentriq, Zinbryta and Zinplava, two are biosimilar antibodies: Amjevita and Flixabi, while the remaining two products are biosimilar Fc-fusion proteins: Erelzi and Benepali.
Surveying the overall recombinant biopharmaceutical pipeline, it is clear from our bioTRAK® database that antibody products continue to dominate the development pipeline. Of the over 400 products in late stage development (Phase 2 through BLA/MAA/NDA application), approximately 70% are antibody related products. The majority of these antibody products (90%) are produced in mammalian systems.
As we enter 2017, there is significant potential for another strong year for antibody product approvals. There are currently 27 products awaiting FDA or EMA approval, 14 of which are mammalian-based antibody products. Eight of the products are full length monoclonal antibodies: an anti-IL-1a Ab, avelumab, brodalumab, dupilumab, guselkumab, ocrelizumab, sarilumab and sirukumab, and five are biosimilars including an adalimumab biosimilar, a bevacizumab biosimilar, a rituximab biosimilar, and two trastuzumab biosimilars.
If we look even further back into the pipeline, there are nearly mammalian-based 260 antibody related products in development, with nearly a quarter in Phase 3. Although many of these products are still in active clinical trials, we expect that some of these products may possibly file for review and be approved before the end of 2017.
As the development and commercialization of antibody products continue to forge ahead with no slowdown in sight, antibodies will remain the cornerstone of the biopharmaceutical market for the foreseeable future.
 We consider antibody products to include full length monoclonal antibodies, antibody fragments (Fab fragments), Fc-fusion proteins, antibody-drug conjugates, and other conjugated antibody products for therapeutic or diagnostic use in humans.
 Sales data for biopharmaceuticals sold in 2016 have not yet been released. Please check back for a new blog revealing 2016 sales in April of 2017.
 Fifteen antibody products have been since withdrawn from the market.
Our article entitled: “Biopharmaceutical Manufacturing Process Validation and Quality Risk Management”, authored by Francisco C. Castello, Ph.D., Brendan Cooney and Howard L. Levine, Ph.D. of BioProcess Technology Consultants, has been chosen as a top five contribution by ISBE for 2016. The article appeared in the May/June 2016 edition of Pharmaceutical Engineering® Magazine. The piece describes process validation today as a continual, risk-based, quality-focused exercise that encompasses the entire product life cycle. If you are an ISPE member, we at BPTC hope you will consider our article when voting for the 2016 best paper award.
Pharmaceutical Engineering has established an “Article of the Year” award to recognize the contribution of authors. Articles are evaluated by a panel of volunteer reviewers according to a number of criteria, concentrating on the importance and timeliness of the subject matter and the quality of the presentation.
At the upcoming BioProcess International West Conference (Feb 27-Mar 2, 2017, San Francisco), Tom Ransohoff, Vice President and Principal Consultant at BioProcess Technology Consultants, will present a paper entitled “Challenges in Forecasting Biopharmaceutical Demand and the Value of Flexibility.” In this talk, Mr. Ransohoff will review the sources of uncertainty in forecasting demand for biopharmaceutical capacity and will describe how this uncertainty is linked to the value of flexibility in manufacturing facilities and strategy.
Frank Riske, Ph.D., Senior Consultant at BioProcess Technology Consultants will be delivering the Keynote Address entitled: Biopharmaceuticals: Past, Present & Future at the 8th Annual PEGS Europe Conference in Lisbon, Portugal. His presentation will cover the evolution of bioprocessing starting with the production of molecules such as insulin, HGH and alpha-interferon and bringing us up to today; a market dominated by monoclonal antibodies but where gene and cell therapy have become increasingly commonplace, biogenerics have made their mark and a number of new therapies are in the works.
Innovative cell and gene therapies and the resurgent interest in ADC’s (antibody drug conjugates) are emerging therapies that are creating these challenges. The roundtable discussion entitled; Outsourcing and Biomanufacturing Challenges for Emerging Therapies, at BIO 2016 focused on demands for CMO services associated with these therapies. Patti Seymour, Senior Consultant at BPTC moderated a panel consisting of Mark Angelino, bluebird bio; Chris Chen, WuXi Biologics; and Andreas Weiler, Lonza: three respected industrial strategic outsourcing thought leaders.
Topics addressed by the panel included forecasting the demand for CMO services and the associated issue of capacity planning. Within this context are the concerns about process design and control as well as regulatory framework related issues such as batch definition when evaluating centralized versus decentralized models for cell therapy. Another discussion point addressed the complexities of supply chain when managing four or more CMC programs per ADC product.
One approach to services planning suggested by the panel begins by sorting the preclinical and clinical pipelines in these therapeutic areas and identifying the short and long term technology implications and capacity needs. Everyone agreed these emerging therapies will represent a learning curve for CMO’s and embody a step-up in risk for both innovators and CMOs.
However, the panel agreed that allogeneic and autologous cell therapies, gene therapies with their associated viral vectors and delivery modes, and novel antibody-linker-toxin ADC combinations represent potent disease therapy options and have the potential to cure disease. These therapies are gaining traction and have great promise. BPTC has a number of client projects in all three areas and is witnessing rapid innovation within these emerging therapies.