IS THE LOWLY TABLET IN FOR A COMEBACK FOR RHEUMATOID ARTHRITIS?
It was interesting to read that in August, Pipex Pharmaceuticals, Inc. acquired an oral, once-daily medication which company officials hope will be an effective treatment for rheumatoid arthritis.
Actually, this is more than interesting - it is downright exciting. Exciting because many patients do not like to have to come into the office for 2 to 3 hours of an intravenous infusion. Exciting because many patients are tired of injecting themselves weekly, or even twice-monthly. Exciting because this is a "biologic" agent without the costly accoutrements of the biologics as we know them today: the complicated and expensive injection "pen" we see with Humira and Enbrel; the infusion equipment needed for Remicade, Rituxan and Orencia.
How the new tablet might work
Oral dnaJP1, as this new drug is currently called, was developed using computer-aided drug design techniques. It is a short synthetic peptide derived from a heat shock protein dnaJ.
Heat shock proteins and dnaJ are produced when cells are under stress, such as in cases of the inflammatory/autoimmune disease, rheumatoid arthritis.
The mechanism of action of dnaJP1 depends on causing T-cell function to produce less inflammation and more regulation from the immune system. So, the inflammation due to the disease rheumatoid arthritis is inhibited.
What the studies show so far
Oral dnaJP1 is considered a new chemical entity. Recently, a Phase II clinical trial involving 160 rheumatoid arthritis patients was completed. A sense of the confidence being shown in this drug might be construed from the fact that this trial was supported by a $5 million dollar grant from the National Institutes of Health.
This study did find a progressive improvement in those patients taking dnaJP1; and by the end of the study more patients succeeded on dnaJP1 compared to those taking placebo. Improvement continued even after patients stopped taking dnaJP1. In addition, oral dnaJP1 resulted in an 80% reduction in the production of tumor necrosis factor (TNF) by T-cells in the laboratory. Remember, that Enbrel, Humira and Remicade are effective mostly due to their TNF-reducing effects.
Other studies using animals with an arthritis similar to rheumatoid arthritis showed that in combination with Enbrel dnaJP1 showed a significant reduction in arthritis.
Although it is certainly too early in the research life of oral dnaJP1 to make any written-in-stone conclusions, because it is an oral drug which might indeed have prolonged benefit in the treatment of rheumatoid arthritis it may eventually be found to have an advantage over the other biologics now available. The initial sense is that oral dnaJP1 may have less toxicity compared to the injectable biologics. (Recall the recent concerns regarding fatal fungus infections in rheumatoid arthritis patients using Enbrel, Humira and Remicade; and the even more recent concerns regarding PML in rheumatoid arthritis patients on Rituxan.) It could prove to be a force to reckon with in combination with the currently available TNF-inhibiting biologics, as shown by the initial animal data. Finally, the staying power of dnaJP1 after a patient ceases taking the drug, may indicate that beneficial "remodeling" of the immune system has resulted from a course of dnaJP1.