August 07, 2019
By Reuters Staff
NEW YORK (Reuters Health) - Patients with the rare genetic disorder familial chylomicronemia syndrome (FCS), who are unable to efficiently break down triglycerides in the blood, saw a dramatic decline in those levels after treatment with Ionis Pharmaceutical's volanesorsen, according to results from a phase III randomized controlled trial.
The findings, published in Thursday's New England Journal of Medicine, led to the drug's approval in the European Union but not in the United States.
Volanesorsen produced a 77% drop in mean triglyceride levels within three months among 33 volunteers at a time when the 33 placebo recipients had an 18% increase. All the volunteers were on a low-fat diet.
FCS, which is believed to affect 3,000 to 5,000 people worldwide, results in the accumulation of fat particles called chylomicrons in the blood. It produces triglyceride levels 10 to 100 times above normal.
The condition can spark severe abdominal pain due to an inflammation of the pancreas, organ and nerve damage and fatty deposits in the skin. Patients need to be on a fat-free diet and abstain from alcohol.
In the double-blind trial lasting 52 weeks, volanesorsen recipients saw a drop in mean triglyceride levels of 1,712 mg/dL, whereas placebo patients had an increase of 92.0 mg/dL (P
Fifteen of the 33 volanesorsen recipients unexpectedly developed thrombocytopenia, with platelet counts below 100,000/uL.
Two of the 15 saw their platelet levels drop below 25,000/uL, prompting an intense platelet-monitoring program. None of the placebo recipients had that problem.
Twenty of the 33 had injection-site reactions from their weekly self-administered subcutaneous injections, another adverse event not seen in any placebo patients.
Only 19 of the 33 volanesorsen recipients completed the 52-week test versus 31 of the 33 assigned to the placeb group. In the volanesorsen group, nine patients were withdrawn because of adverse events, four voluntarily withdrew, and one was withdrawn for nonadherence.
"Volanesorsen treatment effects were sustained for 6 months, at which time triglyceride levels were lower by a mean of 53% in the volanesorsen group as compared with a 25% mean increase in the placebo group," said the research team, led by Dr. Joseph Witztum of the University of California, San Diego.
The drug, to be sold by under the brand name Waylivra, seemed to work regardless of what type of genetic defect cause the patients' FSC.
Ionis and its majority-owned subsidiary, Akcea Therapeutics, paid for the study, known as APPROACH.
European approval came in May, eight months after the U.S. Food and Drug Administration rejected Ionis' new drug application for Waylivra. The companies said it is talking with regulators in the U.S. and Canada about the rejection. A spokeswoman did not respond to a question about why the FDA declined to approve the drug.
The APPROACH study was done at 40 centers in 12 countries.
N Engl J Med 2019.(c) Copyright Thomson Reuters 2019. Click For Restrictions - https://agency.reuters.com/en/copyright.html