Seven novel antibody therapeutics (begelomab, bezlotoxumab, brodalumab, ixekizumab, obiltoxaximab, sarilumab, reslizumab) are undergoing regulatory review as of December 2015, and thus may gain their first approvals in 2016. Commercial late-stage antibody therapeutics development has exceeded expectations by increasing from 39 candidates in Phase 3 studies as of late 2014 to over 50 as of late 2015. Of these candidates, transitions to regulatory review by the end of 2016 are projected for 8 (atezolizumab, benralizumab, bimagrumab, durvalumab, inotuzumab ozogamicin, lebrikizumab, ocrelizumab, tremelimumab). Other “antibodies to watch” include 15 candidates (bavituximab, bococizumab, dupilumab, fasinumab, fulranumab, gevokizumab, guselkumab, ibalizumab, LY2951742, onartuzumab, REGN2222, roledumab, romosozumab, sirukumab, Xilonix) undergoing evaluation in Phase 3 studies that have estimated primary completion dates in 2016. As evidenced by these therapeutics, the biopharmaceutical industry has a highly active late-stage clinical pipeline that may deliver numerous new products to the global market in the near future.
2015: An extraordinary year for first marketing approvals of antibody therapeutics
The number of novel antibody therapeutics that received a first marketing approval in 2015 exceeded expectations, with 8 (alirocumab (Praluent®), elotuzumab (Empliciti®), evolocumab (Repatha®), daratumumab (Darzalex®), dinutuximab (Unituxin®), idarucizumab (Praxbind®), mepolizumab (Nucala®), necitumumab (Portrazza)) granted their first approval as of late December. A total of 9 antibody therapeutics were granted a first US approval in 2015, including all 8 antibodies noted above as well as secukinumab (Cosentyx®), which received a first approval in Japan in 2014. In the European Union, the European Commission also granted marketing approvals to 9 antibody therapeutics in 2015, including 5 antibodies noted above ((alirocumab (Praluent®), evolocumab (Repatha®), dinutuximab (Unituxin®), idarucizumab (Praxbind®), mepolizumab (Nucala®)) and 4 products that had been previously approved in another country. A table of therapeutic monoclonal antibodies approved or in review in the European Union or the United States can be found in the Members Only section of The Antibody Society’s website.
AIRR Community: “Look Ma, In the News Again!”
Another example of the critical importance of data sharing in immune profiling and the need for data standards in the recent editorial “No Sample Left Behind” in Nature Biotechnology, 33(10). Explicit mention of the AIRR Community May Meeting (through a link to PDF of the schedule) means that not only do people think this is important, but the AIRR Community is starting to see some recognition.
I love this quote from the article: “For the moment, however, cross-insitutional efforts remain the exception rather than the rule. For immune profiling research to truly fulfill its potential, now is the time for the community to come together and agree on standardized sample collection and storage and the benefits of pooling data. We must open up the freezers and unlock the data. No sample should be left behind.“
AIRR Community efforts mentioned in Nature
The Nature article “The Cell Menagerie: Human Immune Profiling” by Marissa Fessenden (Nature V. 525, Sep 17, 2015) discusses the importance of vaccines and understanding the immune response. A large number of the groups mentioned in the article are key players in the AIRR Community, including G. Georgiou (UT Austin), Steve Kleinstein (Yale), Lindsay Cowell (UT Southwestern Medical School), and Jamie Scott (Simon Fraser University). An unintended shout out to the AIRR Community’s work!
Report from the First AIRR Community Meeting (May 29 – June 1, 2015)
Final Report: Community Meeting I – Analysis, Management and Sharing of Antigen Receptor Repertoire (AIRR) Sequence Data 29 May – 1 June 2015 Simon Fraser University, Vancouver, BC, Canada This first meeting of the AIRR Research Community brought together experts in the production and analysis of antigen receptor repertoire (or adaptive-immune receptor repertoire; AIRR) data with ethicists, data-security personnel, IP and legal experts, and representatives from funding agencies, to discuss the challenges involved with sharing and comparing this new and expanding type of data. About 70 people attended the meeting, which was organized as a series of workshops addressing topics such as data production quality control, data analysis and integration, and the legal, ethical and IP considerations in sharing AIRR sequence data.
This Community Meeting was motivated by the fact that many academic labs, biomedical research institutions, and pharmaceutical companies are applying next-generation sequencing (NGS) technology to understand adaptive-immune receptor (antibody/B-cell & T-cell repertoires) repertoires. Given NGS technology, it is now possible to sequence millions of molecules from an AIRR, as a means of describing this aspect of the immune response in great detail. These data are now critical for studies of autoimmune diseases, development of vaccines, therapeutic antibodies and cancer immunotherapies, for monitoring clinical trials, and for other developments in immunological research and patient care. However, storing and analyzing these data have become rapidly escalating challenges. The value of AIRR data will increase substantially if researchers can share and compare data among studies and institutions; but at present a common database format and common platforms do not exist for sharing these data. Beyond these bioinformatics challenges, IP, ethics and legal challenges thwart our ability to share and compare AIRR data.
The main outcome of this first Community Meeting was the consensus opinion that sharing AIRR data is essential to the development of this field, and that the community should commit to developing a common repository for AIRR data. To that end, we have formed Working Groups focused on: (1) determining a minimal set of metadata and associated data to include when publishing AIRR data or submitting them to a common database, (2) developing common biologic and bionformatic standards for validating approaches and protocols common to the AIRR Community (3) developing platforms for facilitating sharing of AIRR data, and (4) producing a white paper explaining the goals of the AIRR community. The overall goal coming out of the meeting was to continue to self-organize the community involved in producing and analyzing AIRRs. This AIRR-1 Community Meeting was supported by CIHR, NIH, GenMab, The Antibody Society, CHAVI, the IRMACS Centre, and Simon Fraser University.
