Biotehc firm Rigel’s (RIGL) rheumatoid arthritis drug candidate R788 did not meet its primary endpoint in Phase IIb clinical trial, probably putting in question the company’s goal of securing a R788 partner by the first half of 2010.
In a odd twist, the main reason R788 failed the efficacy portion of the 219-patient study is because of unexplained improvement seen in the placebo group. Patients taking the placebo started showing RA symptom improvement in week six, and again after the third month of the trial.
The placebo group consistently beat out the group receiving the drug. Improvement in RA symptoms was recorded using a scale developed by the American College of Rheumatology. In three subgroups – patients seeing score improvement of at least 20 percent, 50 percent, and at least 70 percent — the placebo beat R788.
When looked at a different way in the Phase IIb trial, R788 did significantly better than the placebo group when blood tests were used to test inflammation reduction among patients.
What is confounding is that R788 did well vs. placebo in other trials. In a separate Phase II study, it showed consistent efficacy, and also managed to set aside worries about potential blood pressure side effects.
Why the big improvement among placebo-takers, other than R788 simply doesn’t work? It may never be known. Possible explanations could be a poor trial setup, problems with the scale, or poor monitoring of patients, all of which were previously on other RA drugs.
The way the drug failed the trial likely means that more trials are forthcoming. It almost certainly won’t be the last study of R788.
For one, R788 is being tested as a treatment for other conditions, including lupus and B-cell lymphoma.
But the big market for the drug clearly is RA, which affects more than 2 million Americans. In all its forms, arthritis is the leading cause of disability in the U.S, and one that affects more than half of seniors.
It would seem likely that a Phase III trial for R788 in RA will still be lined up.
What appears to have happened is Rigel executives collectively stuck out their necks in a risky trial that tried to show statistically significant efficacy in patients that did not respond to other RA drugs.
In a very strange way, the plan backfired. But that does not appear to rule out R788 as a potential RA treatment.
Mike Tarsala
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