March 16th, 2011
Posted by Shane Climie, Ph.D.
On March 9, 2011, the U.S. Food & Drug Administration approved Benlysta® (benlimumab) for the treatment of systemic lupus erythematosus. Benlysta is the first new drug approved for the treatment of lupus in more than 50 years: a triumph of genomic medicine. The drug was born of a partnership, dating back some 18 years, between biotech Human Genome Sciences and multinational pharma GSK. The Benlysta story is an interesting example of how molecular biology and genomic technologies can be applied to create new treatments for challenging diseases, even though the timeline extended well beyond what was anticipated by the lofty projections made in the earliest days of genomic medicine some 20 years ago.
Benlysta is a monoclonal antibody that was developed by HGS and GSK from antibodies that were provided by Cambridge Antibody Technology (which was acquired by AstraZeneca and is now part of AZ’s biologics arm, MedImmune). It acts against B-lymphocyte stimulator (BLyS), which is believed to increase the production of white cells that attack healthy tissue in lupus patients.
There are at least a couple of key breakthroughs that ultimately paid off with the approval of Benlysta.
- First, researchers at HGS – well known as a pioneer in genomic medicine – applied tremendous effort to clone and characterize many human genes in the hopes of identifying drug targets and, eventually, protein-based therapeutics. BLyS, the target of Benlysta, was identified by HGS researchers as a member of the TNF family, which at that time was well recognized as a member of a family of cytokine proteins that can cause cell death and are useful as cancer therapeutics. By looking under the spotlight provided by the earlier discovery of TNF and other cytokines, HGS was able to isolate the BLyS gene (and many others). The expression profile of BLyS and functional studies (using purified, recombinant BLyS) revealed that inhibition of this protein might be an effective treatment for conditions such as lupus, which are B-lymphocyte mediated. Genetic sleuthing had laid the foundation for an assault on lupus.
- Second, BLyS was among the first generation of protein targets that were tackled via phage display, ultimately leading to the construction of Benlysta, a human monoclonal antibody that was assembled from components that were encoded within recombinant libraries of antibody-fragments. A series of regulatory hurdles were ultimately overcome, paving the way for the approval of this drug. All told, it took about 12 years from the cloning and characterization of the BLyS gene to getting Benlysta out the regulatory door. This is an interesting example of the power of genomic technologies, broadly, and genetic engineering, in particular.
Although armed with powerful tools and solid rationale, drug discovery and development generally continues to be a lengthy and extremely windy road with numerous potholes along the way.
Do you think that current technologies are speeding up the process? Or, do they only raise further questions that might slow things down in the long run? I’m interested to see how quickly companion diagnostics and other technologies will enhance and improve the drug development process. What technologies are you watching in this space? Please share your thoughts below.