Ionis Pharmaceuticals, Inc. (NASDAQ: IONS) today announced that pelacarsen, formerly known as AKCEA-APO (a)-LRx, and licensed by Novartis (NYSE: NVS) for exclusive worldwide development and commercialization, continues to advance in the clinic as the potential first-in-class treatment for lipoprotein (a) or Lp(a)-driven cardiovascular disease.

The Novartis pivotal Phase 3 cardiovascular outcomes study of pelacarsen, Lp(a) HORIZON (NCT04023552), has reached 50% enrollment with a target goal of 7,680 trial participants.

Pelacarsen is an investigational antisense medicine that uses Ionis' proprietary Ligand Conjugated Antisense (LICA) technology platform. It is designed to inhibit the production of apolipoprotein(a) in the liver to target elevated Lp(a) levels, an independent genetic risk factor for cardiovascular diseases (CVD), that are determined at birth and cannot be controlled with diet or exercise. High Lp(a) levels are associated with significant risk of cardiovascular disease, including heart attacks and strokes. There are no approved pharmacological therapies to effectively lower Lp(a).

'We are pleased by Novartis progress in advancing the Lp(a) HORIZON study and enrolling nearly 4,000 study participants around the world. Pelacarsen represents a potential first-in-class treatment to address a significant unmet need with the potential to become the new standard of care for Lp(a)-driven cardiovascular disease,' said Sotirios 'Sam' Tsimikas, M.D., senior vice president, clinical development and cardiovascular franchise leader at Ionis, who specializes in Lp(a). 'Ionis' vision is that pelacarsen emerges as an effective therapy to improve cardiovascular outcomes through normalizing Lp(a) levels, as there are an estimated eight million people globally living with elevated Lp(a) and cardiovascular disease.'

Data from a Phase 2 study published in the New England Journal of Medicine showed pelacarsen provided potent dose-dependent reductions of Lp(a) compared to placebo, with a favorable safety and tolerability profile in patients who had elevated Lp(a) levels and established CVD. These data support the potential of antisense-mediated reduction of Lp(a) with pelacarsen.

Ionis earned a $25 million milestone payment from Novartis for achieving 50% enrollment in the pivotal Phase 3 study. In 2017, Novartis entered a collaboration agreement with Ionis for pelacarsen. In February 2019, Novartis exercised an option to license the rights to develop and commercialize pelacarsen for targeted cardiovascular therapy for $150 million. Under the terms of the agreement, Novartis is exclusively responsible for worldwide development and commercialization of pelacarsen and Ionis is eligible to receive up to $675 million in regulatory and sales milestones. Ionis is also eligible to receive tiered royalties in the mid-teens to low 20% range on net sales of pelacarsen.

About Lp(a) HORIZON

Lp(a) HORIZON is a pivotal, global multicenter, double-blind, placebo-controlled pivotal Phase 3 study conducted by Novartis. The trial is designed to support an indication for the reduction of cardiovascular risk in patients with established CVD and elevated Lp(a) with 80 mg of pelacarsen administered monthly via subcutaneous administration. The study has a targeted enrollment of 7,680 participants. The estimated study completion date is in 2024.

The primary objectives of the trial are to demonstrate superiority compared to placebo in reducing the risk of expanded MACE (major adverse cardiac events such as cardiovascular death, non-fatal myocardial infarction, non-fatal stroke and urgent coronary re-vascularization requiring hospitalization) in the overall study population with established CVD and Lp (a) 70 mg/dL, and in the population with Lp(a) 90 mg/dL.

About pelacarsen

Pelacarsen, licensed by Novartis for exclusive worldwide development and commercialization, is an investigational antisense medicine designed to reduce apolipoprotein(a) production in the liver to offer a direct approach for reducing circulating lipoprotein(a), or Lp(a), an atherogenic, pro-inflammatory and thrombogenic lipoprotein that induces additional cardiovascular risk independent of LDL-cholesterol, in patients already treated with LDL-C-lowering therapies (such as statins or PCSK9 inhibitors). Elevated Lp(a) is recognized as an independent, genetic cause of coronary artery disease, heart attack, stroke and peripheral arterial disease. Currently, there is no effective drug therapy to specifically and robustly lower elevated levels of Lp(a). Lp(a) levels are determined at birth and, therefore, lifestyle modification, including diet and exercise, does not impact Lp(a) levels. Even patients with LDL-C lowered to target levels (

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