A Journey through Anti-inflammatory Drug Discovery
The presentation delivers a brief insight into the evolving principles of the inflammatory process that underpin the history and current driving force of future drug discovery for the treatment of auto immune diseases like rheumatoid arthritis (RA) to cancer, neurogenerative disease and fibrosis.
Over the last 70 years inflammatory research and auto-immune disease understanding has driven a paradigm shift in drug research and delivery from anti-symptomatic drugs like Ibuprofen to disease modifying biologicals like anti-TNFa antibodies, delivering greater efficacy and even remission to RA patients. Key historical stepping stones along the way have been the initial discovery of steroids and NSAIDs in the 1950s, then with the advent of biological drug technology in the 1990s, the development of a battery highly specific and effective anti-cytokine biologicals, which have subsequent paved the way for modern day cytokine signalling JAK enzyme inhibitors.
So, what’s the future? One can get a good view of the future vista of anti-inflammatory drugs by going back in time to the very start of the current drug discovery pipeline. Current early drug discovery projects are the source of future drugs to come on the market in the next 10 years or so. Therefore with the help of competitive intelligence database engines like Cortellis, the number of currently active projects active in early drug discovery can be visualised and fingerprinted by drug target. Not surprisingly, the majority of these projects are looking for biosimilars or improvements in existing the drugs, but interesting new targets being progressed are dominated by modulators of bromodomains, Toll receptors and in particular inflammasomes. Furthermore the discovery in 2015 that small molecules can inhibit IL-1 production by inflammasomes and that IL-1 is clinically linked to angiogenesis and lung cancer, has catalysed a massive investment in inflammasome research with new drugs just now getting into the clinic in 2019.
Prior to the drug discovery pipeline entry, basic disease research provides the innovation and fuel to generate and nurture new projects and ideas. Currently new anti-inflammatory research areas aim to pursue gaps in our current disease understanding to identify new therapeutic opportunities. For example, these research themes range from blocking auto-immune disease initiation, modulation of immune cell metabolism to enhancing resolution of inflammation and promoting a healthy gut microbiome.
Overall anti-inflammatory drugs have provided RA patients with highly effective improvements in disease therapy, yet there are still significant unmet needs in that only minority of RA patients achieve remission. Greater insight is needed into understanding the clinical heterogeneity and causes of diseases like RA and how drug management can be personalised to delivery greater therapeutic efficacy.