After Stumbling with Waylivra, Akcea Therapeutics' Lipid Drug Shows Promise

Heart

Akcea Therapeutics, based in Cambridge, Massachusetts, and Ionis Pharmaceuticals, headquartered in Carlsbad, California, released positive topline data from a Phase II trial of AKCEA-APO(a)-LRx in cardiovascular disease and lipoprotein(a).

The Phase II trial was designed to evaluate the safety and tolerability of the compound and to help choose dose information for the planned Phase III trial that will look at cardiovascular outcomes. The Phase II trial evaluated 286 patients with established cardiovascular disease and high Lp(a), which is three times the upper limit of normal. All patients were treated for at least six months. Some patients were treated up to 12 months.

The drug showed significant dose-dependent decreases of Lp(a) compared to placebo. The most common side effects were reactions at the injection site and were mostly mild and only occurred in a minority of patients. Elevated Lp(a) is a hereditary risk favor for cardiovascular disease that can’t be controlled well with diet and exercise, or with existing cholesterol medications.

“These data represent an important step forward for patients who have significant risk of premature death from cardiovascular disease due to their high levels of Lp(a),” said Paula Soteropoulos, chief executive officer of Akcea, in a statement. “In this large Phase II study AKCEA-APO(a)-LRx, robustly lowered Lp(a) with a favorable safety and tolerability profile. In addition, the data from this study support the potential to treat patients with convenient, low volume monthly doses. These results are also encouraging as we continue to develop our LICA pipeline.”

The drug is being developed as a strategic collaboration between Akcea and Novartis. If Novartis exercises an option to license the drug after the successful completion of an end of Phase II meeting with the U.S. Food and Drug Administration (FDA), Novartis will pay Akcea a $150 million milestone payment, half of which will go to Ionis.

If Novartis does exercise the option, it will be responsible for all future development of the drug, including a global Phase III cardiovascular outcomes trial. And if the drug is approved, Novartis will handle worldwide commercialization activities.

Akcea keeps the right to co-commercialize any successful drug via its specialty sales force.

This is good news after Akcea was shocked by an FDA rejection of its Waylivra (volanesorsen) for a rare lipid disorder, familial chylomicronemia syndrome (FCS) on August 28. It was particularly surprising, given that in May an FDA advisory committee recommended the drug with a vote of 12 to 8. The FDA typically follows advisory committee recommendations, although they are not obligated to. That was one aspect of the drug’s rejection that was surprising; the other was the company did not publicly disclose the reasons why the drug was rejected.

At the time, Soteropoulos stated, “We are extremely disappointed with the FDA’s decision. FCS is an ultra-rare and debilitating disease. Our disappointment extends to the patient and physician community who currently do not have a treatment available to them. We continue to feel strongly that Waylivra demonstrates a favorable benefit/risk profile in people with FCS as we reflected in the positive outcome from our Advisory Committee hearing in May.”

Not long after, a patient advocacy group, the FCS Foundation, spoke up, demanding the FDA reconsider its decision. In a statement to BioSpace, the foundation said, “This FDA decision leaves FCS patients with no clinical treatment for the disease. … Despite the FDA having a department that is committed to understanding the impact and burden of rare diseases, it appears they have not taken the patient experience or testimony into consideration in their decision to not approve Waylivra.”

And only a day or two later, the company indicated it planned to cut around 10 percent of its workforce as a result of the rejection.

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