Akcea Therapeutics, a subsidiary of Ionis Pharmaceuticals, has announced the initiation of a phase 2b dose-ranging study of AKCEA-APO(a)-LRx in patients with hyperlipoproteinemia(a) and established cardiovascular disease. The goal of the study is to determine the dose level and frequency for use of AKCEA-APO(a)-LRx in a planned phase 3 cardiovascular outcome study.
AKCEA-APO(a)-LRx is part of Akcea's strategic collaboration with Novartis to develop and commercialize drugs to treat patients who are at high cardiovascular risk due to inadequately treated lipid disorders. AKCEA-APO(a)-LRx inhibits the production of apolipoprotein(a), or Apo(a) protein, thereby reducing lipoprotein(a), or Lp(a). Apo(a) is a very atherogenic and thrombogenic form of low-density lipoprotein (LDL). Elevated Lp(a) is recognized as an independent, genetic cause of coronary artery disease, heart attack, stroke and peripheral arterial disease. AKCEA-APO(a)-LRx is an antisense drug that uses Ionis' advanced LIgand Conjugated Antisense, or LICA technology. The enhancements offered by Ionis' LICA technology can potentially provide greater patient convenience by allowing for significantly lower doses and less frequent administration as compared to non-LICA drugs.
"There is currently no effective drug therapy to specifically and robustly lower elevated levels of Lp(a), which is recognized as an independent, genetic cause of cardiovascular disease. We believe addressing elevated Lp(a) is the next important horizon in lipid-focused therapy and, through our collaboration and option agreement with Novartis, we plan to develop AKCEA-APO(a)-LRx to treat patients with established cardiovascular disease in whom elevated Lp(a) plays a causal role in their disease," said Paula Soteropoulos, chief executive officer at Akcea Therapeutics. "Following the achievement of specified development milestones and prior to the initiation of a phase 3 study, Novartis will be able to exercise its option to license the drug. Upon licensing, Novartis will be responsible for worldwide development and commercialization of AKCEA-APO(a)-LRx."
The randomized, double-blind, placebo-controlled, dose-ranging phase 2b study will evaluate the safety and efficacy of different doses of AKCEA-APO(a)-LRx in approximately 270 patients with hyperlipoproteinemia(a) and established cardiovascular disease. Akcea plans to report top-line data from this study in the middle of 2018.
In January 2017, Ionis and Akcea initiated a strategic collaboration and option agreement with Novartis to develop and commercialize AKCEA-APO(a)-LRx and AKCEA-APOCIII-LRx. This collaboration can accelerate Akcea's ability to deliver these potential therapies to the large populations of patients who have high cardiovascular risk due to inadequately treated lipid disorders. Ionis and Akcea have received a $75 million upfront option payment and a $100 million equity investment in Ionis. Novartis has also agreed to purchase an additional $50 million in Akcea equity. For each drug, upon option exercise, Novartis will pay Ionis and Akcea a $150 million license fee, will initiate a global phase 3 cardiovascular outcome study in high-risk patients and will be responsible for worldwide development and commercialization activities, if approved. Akcea plans to co-commercialize any licensed drug commercialized by Novartis through its specialty sales force focused on lipid specialists on terms and conditions to be agreed with Novartis.