Isis Pharmaceuticals has opted to throw in the towel on its rheumatoid arthritis program for ISIS-CRPRx after a Phase II study failed to produce a statistically significant improvement over a placebo. But the biotech ($ISIS) says it will continue to plug away at studies of the antisense treatment for other diseases, including a mid-stage trial for atrial fibrillation due to read out next year.
Investigators say that ISIS-CRPRx cut levels of the inflammatory C-reactive protein by up to 67% for the high dose, but they said the trial was done in by an unexpectedly high placebo response, which compared the signs and symptoms of the disease. Isis recruited 51 patients for the study and provided three doses ranging from 100 mg to 400 mg.
The Phase II pratfall closely follows a hit for the company's diabetes drug APOCIIIRx. Just weeks ago Isis reported that after 13 weeks of weekly injections of ISIS-APOCIIIRx--designed to hit the "off" switch on a gene that produces the apolipoprotein C-III protein, involved in triglyceride regulation--there was a 72% plunge in fatty particles and a 40% spike in HDL, or good cholesterol, along with improved insulin sensitivity among the 11 patients with Type 2 diabetes in the study. And near the start of this year Isis and its partner Genzyme won an approval for Kynamro for rare cases of homozygous familial hypercholesterolemia.
"CRP is strongly associated with the presence and severity of many diseases, including numerous inflammatory and cardiovascular diseases," said Richard Geary, senior vice president of development at Isis. "In this study, by treating patients with chronically elevated CRP with ISIS-CRPRx, we hoped to accomplish three things: to confirm in patients the substantial CRP-lowering activity we observed in our earlier clinical studies, to gain additional experience with the drug before testing it in more severe indications, and to evaluate whether lowering CRP correlates with an improvement in RA symptoms. The study accomplished its goals. We are pleased with the consistency of CRP lowering across all of our clinical studies, but we are disappointed that we did not see a greater impact on RA symptoms in these patients. While we do not plan to further develop ISIS-CRPRx for RA, we do plan to continue to evaluate ISIS-CRPRx to treat other diseases."
- here's the press release