ISIS-APOCIIIRx: Phase II data

Data from 26 patients with high to severely high triglyceride levels on stable doses of fibrates in cohort 1 of a double-blind Phase II trial showed that once-weekly 200 and 300 mg subcutaneous doses of ISIS-APOCIIIRx each met the co-primary endpoints of reducing APOCIII and triglyceride levels from baseline to week 13 vs. placebo. Specifically, ISIS-APOCIIIRx reduced APOCIII levels by 59.4% at the 200 mg dose and by 70% at the 300 mg dose vs. 2.2% for placebo (p<0.0001 for both). ISIS-APOCIIIRx reduced triglyceride levels by 49.7% at the 200 mg dose (p=0.03) and by 63.9% at the 300 mg dose (p=0.003) vs. 7.7% for placebo. Additionally, 5 of 8 patients in the 200 mg ISIS-APOCIIIRx arm and 7 of 10 patients in the 300 mg ISIS-APOCIIIRx arm achieved triglyceride levels of <150 mg/dL at week 13 vs. 0 of 8 patients receiving placebo. Mean baseline fasting triglyceride levels were 457 mg/dL for placebo patients, 282 mg/dL for patients receiving low-dose ISIS-APOCIIIRx and 384 mg/dL for patients receiving high-dose ISIS-APOCIIIRx.

Furthermore, ISIS-APOCIIIRx significantly reduced APOCIII-associated VLDL particles from baseline to week 13 by 65.9% in the 200 mg arm (p=0.0006) and by 77.4% in the 300 mg arm (p=0.0003) vs. an increase of 8.4% for placebo. ISIS-APOCIIIRx also significantly increased HDL-C from baseline to week 13 by 47.4% in the 200 mg arm (p=0.02) and by 51.8% in the 300 mg arm (p=0.008) vs. 5.9% for placebo. Isis said there was no significant increase in LDL-C or non-HDL-C vs. placebo. ISIS-APOCIIIRx was well tolerated with injection-site reactions, including erythema, reported as the most common adverse events. There were no flu-like symptoms, no elevations of liver enzymes >3 times the upper limit of normal, no abnormalities in renal function and no clinically meaningful changes in other laboratory values reported. ...