Akcea Therapeutics and Ionis Pharmaceuticals rolled out successful Phase 2 study results Wednesday showing their drug candidate lowered Lp(a), short for lipoprotein(a), levels in patients with cardiovascular disease, setting up a decision for its research partner Novartis to exercise a licensing option and lead the therapy into a Phase 3 trial.
The drug, an antisense oligonucleotide called AKCEA-APO(a)-Lrx, significantly reduced Lp (a) levels, which are an independent genetic factor seen by many cardiologists as a risk factor for cardiovascular disease. Additionally, patients given the highest dosage levels achieved stronger, clinically meaningful results in lowering Lp(a) levels below a recommended risk threshold.
Through a previous research deal, Novartis will have 60 days after the companies have an end-of-Phase-2 meeting with the Food and Drug Administration to exercise a licensing option. If the Swiss pharmaceutical giant chooses to go forward, it will lead the late-stage trial and pay a $150 million milestone payment split evenly between Akcea and Ionis. A Novartis spokesperson told BioPharma Dive the company is still evaluating the data.
After initially presenting the study at the American Heart Association Scientific Sessions on Nov. 10, Akcea and Ionis rolled out the results in a Tuesday news release. They previously announced positive top line data in September.
As a hereditary risk factor for cardiovascular disease, Lp(a) cannot be well controlled through diet, exercise or cholesterol-lowering therapies.
“A drug that reduces Lp(a) could be a paradigm shift for the cardiovascular community,” Sotirios Tsimikas, Ionis vice president of global cardiovascular development, said in a Nov. 12 statement. “Physicians are looking for a tool to treat their patients who today have no pharmacological option to sustainably reduce their Lp(a) levels below 50 mg/dL, the threshold for a Lp(a)-driven cardiac event such as heart attack or stroke.”
Akcea and Ionis’ therapy could be that option, data from a Phase 2 trial suggests. The study divided roughly 270 patients with cardiovascular disease and elevated Lp(a) levels into five cohorts along with a placebo group. Generally, the data showed higher dosing and more frequent treatments led to more pronounced efficacy.
Investment bank Cowen & Co. was also impressed. In a Nov. 12 note, analyst Ritu Baral called it “excellent evidence of superior efficacy and safety” with a “relatively benign” adverse effects profile.
On the safety element, discontinuation rates were similar between active and placebo groups at 12% and 15%, respectively, with mainly mild and moderate adverse events.
Akcea and Ionis executives asserted the results clear the way for Phase 3 testing. But Novartis’ opinion on that topic will prove to be crucial.
Through a deal between the three companies in January 2017, Novartis got a stake in two cardiovascular drugs, one being AKCEA-APO(a)-Lrx. After paying $225 million upfront in cash and equity investments, Novartis also agreed to pay a total potential value in royalties, licensing fees and milestones of more than $1.6 billion.
As part of the deal, Novartis will have the option to extend its licensing deal within 60 days of an end of Phase 2 meeting with the FDA on this study. Cowen’s Baral expects that meeting to happen by the end of 2018.
If Novartis chooses to exercise the option, it will pay $75 million each to Akcea and Ionis in a milestone payment, and then lead the Phase 3 testing.
With Phase 2 data that hit all primary and secondary endpoints, Akcea and Ionis are in a stronger position now than before. It’s particularly welcome news given Akcea recently announced a 10% workforce reduction following an FDA rejection of its rare disease drug candidate Waylivra (volanesorsen).