Akcea Therapeutics reported topline data showing that all doses of its hyperlipoproteinemia candidate lowered lipoprotein(a) levels in a phase 2 study involving 286 patients with cardiovascular disease. If all goes well at the end-of-phase-2 meeting with the FDA, its partner Novartis could license the drug, triggering a $150 million payout for Akcea and Ionis.
The drug, known as AKCEA-APO(a)-LRx, was one of four programs Ionis offloaded when it spun out Akcea in 2015. It is based on Ionis’ ligand-conjugated antisense technology, a platform Ionis says could be used to create drugs that would require lower and less frequent doses than non-LICA antisense medicines.
Ionis tied up with Novartis in January 2017 on two drugs: AKCEA-APO(a)-LRx and AKCEA-APOCIII-LRx, which is being developed for hypertriglyceridemia. The Swiss pharma forked over $75 million upfront, with a potential $1 billion in biobucks to come. If Novartis picks up AKCEA-APO(a)-LRx, it will be responsible for the drug’s phase 3 development and commercialization, while Akcea and Ionis will split the $150 million.
The randomized, double-blind, placebo-controlled study tested a range of doses of AKCEA-APO(a)-LRx in patients with established cardiovascular disease and lipoprotein(a), or Lp(a), levels that, at baseline, were more than three times the upper limit of normal. Lp(a) is a type of soluble protein that binds with lipids to transport them in the blood and has emerged as an independent risk factor for developing vascular disease. It cannot be controlled with diet, exercise or cholesterol-lowering drugs.
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All of the patients in the phase 2 study were treated for at least six months. All doses of AKCEA-APO(a)-LRx resulted in statistically significant reductions in Lp(a) levels compared to placebo. Most patients in the treatment group ended up with Lp(a) levels below the threshold of risk for cardiovascular events.
“Recent data have shown that patients are particularly at risk when their Lp(a) levels go over 50 mg/dL. The data from this study are very encouraging as they show that AKCEA-APO(a)-LRx consistently reduced Lp(a) levels below this risk threshold,” said Sotirios Tsimikas, M.D., VP of global cardiovascular development at Ionis Pharmaceuticals and a professor of medicine and director of vascular medicine at the University of California, San Diego, in the statement. “There are currently no treatment options available to patients that specifically target Lp(a). The introduction of a safe and effective therapeutic would represent a major advance in patient care.”
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The news comes just one month after the FDA rejected Akcea’s volanesorsen, an antisense drug for familial chylomicronemia syndrome. While CEO Paula Soteropoulos said Akcea would “continue to work with the FDA to confirm the path forward,” the company did not specify why the agency nixed the drug, nor did it say how it would move forward with its submission. Shortly thereafter, the company laid off 10% of its workforce.