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| Biotech
Tracker: Chemokine Inhibition For Rheumatoid Arthritis Looks Promising |
August 08, 2003 Tak, Haringman, and colleagues from the University of Amsterdam (The Netherlands) investigators published a compelling phase Ib investigation in the August edition of Annals of the Rheumatic Diseases. The study, sponsored by Pfizer (NYSE: PFE), has shown that inhibiting specific chemokine receptors (in this case, CCR1) can result in clinically relevant biological effects in patients with active rheumatoid arthritis (RA). The paper significantly advances the anti-CCR1 literature as it pertains to the potential management of chronic autoinflammatory conditions. It also suggests that Pfizer is significantly ahead of Schering-Plough (NYSE: SGP), Millennium (NASDAQ: MLNM), Takeda, and other companies interested in developing chemokine inhibitors as anti-inflammatory drugs.
Chemokines, which are similar in structure and molecular action to cytokines like IL-2 and TNFa, regulate cell migration and inflammation. While the promise of these molecules as drug targets is well known, this is the first important report of a human clinical trial using a chemokine inhibitor to treat a chronic, autoinflammatory condition.
The investigation was a 16- active RA patient, randomized, double blind, placebo controlled, clinical trial that assessed the effects of an oral CCR1 blocker. For 14 days, 12 subjects received the drug and 4 received placebo. All patients completed the investigational protocol. Anti-inflammatory advantages at the biological and surrogate marker level that have the potential to translate into clinical advantages were:
reductions in the number of several inflammatory cell lineages in the synovium (the lubricant secreted by, and maintained between, connective tissue such as bone, bursa, or tendon sheaths)
macrophages (p=0.016)
intimal macrophages (p=0.026)
CCR1+cells (p=0.049)
significant decreases in:
overall cellularity
intimal lining layer cellularity
CD4+ T cells
CD8+ T cells.
Cells lacking CCR1 were unaffected. Trends observed toward therapeutic effect were observed for CCR1-blocker, but not placebo, recipients. Adverse effects were not reported.
In spite of the biotech industry’s success with developing new therapies for RA, none cures the condition. Developing orally available small molecules remains attractive. The stage is now set for larger, rigorously controlled investigation of this and other chemokine inhibitors.
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