Isis Pharmaceuticals announced the results from a phase I clinical trial in which ISIS-CRPRx produced statistical reductions in C-reactive protein (CRP) in the cohort with elevated CRP. ISIS-CRPRx was well tolerated at doses up to 600 mg/week. Isis plans to evaluate ISIS-CRPRx in phase II studies in indications that could provide early proof-of-concept in diseases with elevated CRP. Isis plans to initially evaluate ISIS-CRPRx in multiple myeloma and rheumatoid arthritis, and then move to cardiovascular and other diseases.
The phase I study was a blinded, randomized, placebo-controlled, dose-escalation study designed to assess the safety and pharmacokinetic profile of ISIS-CRPRx as well as to assess the initial effects of the drug on baseline CRP levels. ISIS-CRPRx was evaluated in single and multiple doses ranging from 50 mg per week to 600 mg per week in 80 healthy volunteers. In all but one cohort, Isis enrolled subjects who had normal CRP levels. In the 600 mg per week multi-dose cohort, Isis enrolled eight subjects with elevated levels of CRP. The subjects in this cohort had an average CRP level at baseline of approximately 3.0 mg/L.
After only three weeks of dosing, the six subjects who received ISIS-CRPRx had an average CRP level of 0.76 mg/L, which is within the normal range of CRP and represents an average reduction of greater than 70% compared to placebo. Subjects receiving placebo remained elevated above 3.0 mg/L. In all subjects receiving the drug, it was well tolerated with no serious adverse events.