Isis Pharmaceuticals Reports Data From a Phase 2 Study of Isis-CRP Rx in Patients with Rheumatoid Arthritis

Isis Pharmaceuticals, Inc. has announced that patients treated with ISIS-CRPRx achieved rapid, dose-dependent mean reductions of up to 67% in C-reactive protein (CRP) in a Phase II study in patients with rheumatoid arthritis (RA). 

Patients treated with ISIS-CRPRx showed improvements in signs and symptoms of RA; however, these improvements were not statistically significant when compared with those observed in patients in the placebo group, which demonstrated a higher than expected response in both symptom score and CRP reduction. A Phase II study of ISIS-CRPRx in patients with atrial fibrillation is currently ongoing with data anticipated in the first half of 2014.

"CRP is strongly associated with the presence and severity of many diseases, including numerous inflammatory and cardiovascular diseases. 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," said Richard Geary, PhD, senior vice president of development at Isis. "Although we do not plan to further develop ISIS-CRPRx for RA, we do plan to continue to evaluate ISIS-CRPRx to treat other diseases."

The Phase II study was a randomized, placebo-controlled, multiple-dose study in patients with RA who had chronically elevated CRP. In this study, 51 patients received 100 mg, 200 mg or 400 mg dose of ISIS-CRPRx or placebo for 12 weeks. Patients in the study treated with ISIS-CRPRx achieved substantial, dose-dependent reductions in CRP early in treatment that were prolonged through the treatment process. Patients also experienced improvements in the signs and symptoms of RA, as measured by ACR20 and ACR50 scores. These improvements correlated with reductions in CRP, but were not sufficiently greater than improvements observed in the placebo groups to justify further development of ISIS-CRPRx for RA.