Dive Brief:
- 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.
Dive Insight:
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).