Ionis Pharmaceuticals, Inc. announced that topline results from the Phase 2b SOLANO study in patients with hypercholesterolemia demonstrated that 60mg of ION449 (AZD8233) administered monthly achieved a statistically significant 62.3% (p<0.001) reduction in low-density lipoprotein cholesterol (LDL-C) levels after 28 weeks compared to placebo, meeting the study’s primary efficacy endpoint. ION449 was generally safe and well tolerated in this study. However, these results did not achieve pre-specified efficacy criteria and AstraZeneca has decided not to advance ION449 (AZD8233) into Phase 3 development for hypercholesterolemia. 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, M.D., executive vice president, chief clinical development officer at Ionis. “AstraZeneca continues to be a valued collaborator and we look forward to working with them to advance multiple important programs.”
SOLANO (NCT04964557) 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 (AZD8233) as compared with placebo.
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.