NEJM publishes positive clinical results from Phase 2 clinical study of volanesorsen

Isis Pharmaceuticals, Inc. (NASDAQ: ISIS), the leader in RNA-targeted therapeutics, and Akcea Therapeutics, its wholly owned subsidiary, announced today that The New England Journal of Medicine (NEJM) has published positive clinical results from a Phase 2 clinical study evaluating volanesorsen (formerly ISIS-APOCIII_Rx) in patients with very high to severely high triglycerides. This publication follows the December 2014 publication in the NEJM of the positive Phase 2 results from a clinical study of volanesorsen in patients with familial chylomicronemia syndrome (FCS). Volanesorsen is part of Isis' lipid franchise, which is being developed and commercialized by Akcea Therapeutics.

"These publications emphasize the significant interest from the medical community in the therapeutic potential of antisense drugs, such as volanesorsen, to substantially affect novel cardiometabolic targets, like apoC-III," said Sekar Kathiresan, director of preventive cardiology at Massachusetts General Hospital and researcher in medical and population genetics at the Broad Institute of Massachusetts Institute of Technology and Harvard University. "These and other findings from the medical and scientific communities are confirming the importance of apoC-III and triglycerides as risk factors for cardiovascular and metabolic disease. The recent results with volanesorsen indicate that an RNA-targeted antisense approach is proving to be an ideal way to target these risk factors."

"We have consistently demonstrated significant reductions in apoC-III and triglycerides in patients treated with volanesoren. We have also reported significant improvements in glucose parameters in patients with high triglycerides and type 2 diabetes treated with volanesorsen. These data highlight the potential therapeutic value that volanesorsen can bring to patients with serious cardiometabolic lipid disorders. Akcea is building a world class team focused on the development and commercialization of drugs to treat rare lipid disorders. Preparations for global commercialization of volanesorsen are underway," said Paula Soteropoulos, president and chief executive officer of Akcea Therapeutics. "Volanesorsen is the most advanced drug in Akcea's portfolio of lipid drugs. Together with ISIS-APOCIII-L_Rx, our more potent LICA follow on drug for patients with severely high triglycerides, and the other drugs in our pipeline, we have the opportunity to provide complementary therapeutic solutions to physicians treating patients with lipid disorders."

"We continue to see growing interest in the therapeutic potential of our antisense drugs to specifically affect important, genetically validated targets, like apoC-III and Lp(a), that are often not approachable with other therapeutic modalities," said Richard Geary, Ph.D., senior vice president of development at Isis Pharmaceuticals. "The publication of four manuscripts in the last few months in either The New England Journal of Medicine (3 papers) or The Lancet (one paper), represents substantial recognition from the medical community of our technology and its broad applicability to address newly identified targets."

The paper, titled "Antisense Inhibition of APOC3 in Patients with Hypertriglyceridemia" (Gaudet et al, N Engl J Med 2015: published online July 29), reported data from the Phase 2 study of volanesorsen, a double-blind, randomized, placebo-controlled 13-week study designed to assess the safety and activity of volanesorsen in patients as a monotherapy and as an add-on to fibrates. Patients treated with volanesorsen achieved mean reductions of up to 80 percent in apoC-III and up to 71 percent in triglycerides and average increases of up to 46 percent in HDL-C. The efficacy, safety and tolerability of volanesorsen in patients with very high to severely high triglycerides to date support continued development.