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|Isis Reports Phase 2 Data on ISIS-APOCIII Rx Showing Significant Reductions of ApoC-III and Triglycerides in Patients With High Triglycerides Taking Fibrates|
The Phase 2 study of ISIS-APOCIIIRx was a double-blind, randomized, placebo-controlled 13-week study designed to assess the safety and activity of ISIS-APOCIIIRx. The portion of the study reported today was conducted in patients with high to severely elevated triglyceride levels (between 225 and 2,000 mg/dL) on stable doses of fibrates.
Table 1: ISIS-APOCIIIRx Produced Statistically Significant Reductions of Triglycerides, ApoC-III and ApoC-III Associated VLDL in a Phase 2 Study in Patients With High Triglyceride Levels Treated With Stable Doses of Fibrates. Mean % Changes From Baseline at Primary Endpoint.
P value = vs. placebo + fibrate.
After 13 weeks of dosing, robust and prolonged, statistically significant mean percent reductions from baseline in apoC-III, triglycerides and VLDL-associated apoC-III particles were observed in both dose cohorts. Furthermore, patients treated with ISIS-APOCIIIRx demonstrated a rapid, prolonged and statistically significant mean percent increase from baseline in HDL-C in both dose cohorts with no statistically significant increase in low-density lipoprotein cholesterol (LDL-C) or non-HDL-C. The effects of ISIS-APOCIIIRx observed on these lipid parameters were in addition to those achieved with each patient's existing therapeutic regimen of fibrates.
"Patients with very high levels of triglycerides are at significant risk for cardiovascular disease, diabetes, pancreatitis and other complications. For these patients, there are very limited treatment options. Fibrates have been shown to reduce triglycerides; however fibrate therapy is not always effective nor widely used by these patients," said
In this study, 26 patients received either 200 mg or 300 mg dose of ISIS-APOCIIIRx, or placebo via weekly subcutaneous injections. All patients were on stable doses of fibrates with average baseline levels of fasting triglycerides between 282 mg/dL and 457 mg/dL. The three groups of patients were reasonably well balanced in baseline characteristic.
In this study ISIS-APOCIIIRx was found to be generally safe and well tolerated. The most common adverse event (AE) was injection site reactions, which were infrequent and consisted of mild erythema that typically resolved within one to two days. There were no flu-like symptoms, no elevations of liver enzymes greater than three times upper limit of normal, no abnormalities in renal function and no clinically meaningful changes in other laboratory values. There was one patient who, four days after treatment, experienced a transient episode of a rash, low-grade fever, chills and headache, which resolved completely. This event was reported by the investigator as related to treatment, and classified as a serum sickness-like reaction (a serious AE). Subsequent detailed investigations demonstrated that it was not serum sickness.
"We are very encouraged by the two sets of positive data we have reported this summer demonstrating that treatment with ISIS-APOCIIIRx produced highly statistically significant and clinically meaningful reductions in apoC-III and triglycerides, and increases in HDL-C in patients with high triglycerides. In addition, the positive effect of ISIS-APOCIIIRx treatment on lipid parameters, improvements in glucose control and trends toward improvements in insulin sensitivity, suggest that ISIS-APOCIIIRx could have a broad therapeutic profile in addition to triglyceride lowering for patients with severely high triglycerides. We are also pleased with the data reported today. They demonstrate that ISIS-APOCIIIRx is additive to fibrates with robust reductions of apoC-III and triglycerides," said
ISIS-APOCIIIRx is an antisense drug intended to treat patients with severely high triglycerides either as a single agent or in combination with other triglyceride-lowering agents. ISIS-APOCIIIRx targets apoC-III, a gene produced in the liver that plays a central role in the regulation of serum triglycerides. Humans who do not produce apoC-III have lower levels of triglycerides and lower instances of cardiovascular disease. In clinical studies, patients with lower levels of apoC-III and triglycerides exhibit lower cardiovascular event rates. Humans with elevated levels of apoC-III have increased dyslipidemia associated with multiple metabolic abnormalities, such as insulin resistance and/or metabolic syndrome. In addition, the prevalence of type 2 diabetes is increased in patients with elevated triglycerides.
ISIS PHARMACEUTICALS' FORWARD-LOOKING STATEMENT
Isis Pharmaceuticals® is a registered trademark of
D. Wade Walke, Ph.D., Executive Director, Corporate Communications and Investor Relations, 760-603-2741, or Amy Blackley, Ph.D. , Associate Director, Corporate Communications, 760-603-2772