Ionis Pharmaceuticals said AstraZeneca will not advance Ionis’ experimental antisense therapy to treat hypercholesterolemia. Even though topline results from the company’s phase 2b SOLANO study met its primary endpoint, it failed to reach a pre-specified efficacy criteria AstraZeneca had set.
Photo: Eugene Schneider, executive vice president, chief clinical development officer at Ionis
Ionis said ION449 showed a statistically significant 62.3 percent reduction in low-density lipoprotein cholesterol levels after 28 weeks compared to placebo and was generally safe and well tolerated in the study.
AstraZeneca is continuing to analyze the results from the SOLANO study to determine its next steps for the program.
“While the LDL-C reductions seen in high-risk hypercholesterolemia patients on maximum statin therapy were both statistically significant and robust, these results did not meet AstraZeneca’s target product profile criteria to invest in a broad phase 3 development program,” said Eugene Schneider, executive vice president, chief clinical development officer at Ionis. He said the two companies continue to collaborate and work to advance multiple programs.
Hypercholesterolemia, or elevated LDL-C levels in the blood, is an important risk factor for cardiovascular disease, the leading cause of death worldwide. There is a significant unmet medical need for stronger LDL-C lowering therapies in secondary prevention patients with approximately 50 percent who are not meeting their treatment goals despite taking a high-intensity statin. It is estimated that one in six patients with LDL-C >100mg/dL will suffer a second major adverse cardiovascular event over approximately three years.
ION449 (AZD8233) dosed once monthly via subcutaneous administration, is an investigational medicine that uses Ionis’ advanced LIgand-Conjugated Antisense (LICA) technology platform. It is designed to reduce plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 is integrally involved in the regulation of LDL-cholesterol. Genetic studies have shown that individuals with life-long reduction of LDL-C due to reduced function of PCSK9 have substantially reduced risk of cardiovascular disease. Pharmacological inhibition of PCSK9 substantially lowers LDL-C. ION449 is designed to reduce the liver production of PCSK9 and lower the plasma level of LDL-C and thus reduce the risk of cardiovascular disease. AstraZeneca licensed ION449 from Ionis in 2015.
SOLANO was a randomized parallel, double-blind, placebo-controlled phase 2b study in 411 participants with hyperlipidemia LDL-C ≥70 mg/dL and <190mg/dL on maximum tolerated statin and/or ezetimibe. The primary objectives of this study were to assess the efficacy, safety, and tolerability of ION449 as compared with placebo.
Author: Rare Daily Staff
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