Results from Phase 2 study demonstrate patients receiving vupanorsen experienced significant, dose-dependent reductions in triglyceride levels, ANGPTL3 and additional lipid parameters compared to placebo

Favorable safety and tolerability profile demonstrated for LICA platform-based therapy

Results from the Phase 2 study to be published in the European Heart Journal

BOSTON and CARLSBAD, Calif., Aug. 29, 2020 /PRNewswire/ -- Akcea Therapeutics, Inc. (NASDAQ: AKCA), a majority-owned affiliate of Ionis Pharmaceuticals, Inc., and Ionis Pharmaceuticals, Inc. (NASDAQ: IONS), presented data from the Phase 2 clinical trial of vupanorsen (AKCEA-ANGPTL3-LRx) in an online Late Breaking Clinical Trial Session at the ESC Congress 2020, the annual meeting for the European Society of Cardiology.

Vupanorsen is an investigational antisense therapy being developed to treat patients with certain cardiovascular diseases. In the Phase 2 study, vupanorsen met the primary endpoint of significant reductions in triglyceride (TG) levels and multiple secondary endpoints compared to placebo, with a favorable safety and tolerability profile.

"We are very encouraged by the demonstrated efficacy, safety and tolerability profile of vupanorsen," said Damien McDevitt, Ph.D., chief executive officer at Akcea. "There are millions of patients worldwide living with dyslipidemia that puts them at risk of cardiovascular events. By reducing ANGPTL3, vupanorsen has the potential to reduce the risk of cardiovascular events caused by dyslipidemia in many of these patients, thereby addressing a major area of continued unmet medical need. We look forward to working with Pfizer as they continue to advance this important clinical development program."

Vupanorsen was developed using Ionis' proprietary LIgand Conjugated Antisense (LICA) technology platform to reduce the production of angiopoietin-like 3 (ANGPTL3) protein from the liver, a key regulator of triglyceride and cholesterol metabolism.

The goal of the randomized, double-blind, placebo-controlled, dose-ranging Phase 2 study was to assess the safety and efficacy of vupanorsen. A total of 105 patients with hypertriglyceridemia (fasting plasma TG levels >150 mg/dL), type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) were randomized to three dosing cohorts in a 3:1 ratio (vupanorsen: placebo) within each cohort and treated for six months. The dosing cohorts explored different doses and dose regimens vs placebo, with patients receiving either 40 mg or 80 mg every four weeks or 20 mg every week. Participants received either vupanorsen or placebo via subcutaneous injection. Results from the Phase 2 study show:

• Statistically significant dose-dependent reductions in fasting TGs at all dose levels, with the highest mean reduction of 53% at the dose of 80 mg every four weeks (44% mean reduction compared to placebo, P