Delhi: Patients with familial chylomicronemia syndrome when given volanesorsen, reduced the levels of triglycerides to less than 750 mg/dL in 77% of the patients, according to a recently published study in The New England Journal of Medicine.
Familial chylomicronemia syndrome (FCS) is a rare genetic disease characterized by the accumulation of chylomicrons in the blood and recurrent episodes of pancreatitis. It is caused by the impaired functioning of the enzyme lipoprotein lipase (LPL), which is responsible for breaking down chylomicrons in the blood. This leads to an increase in the levels of triglyceride.
Normal triglyceride levels are <150 mg/dL (or 1.7 mmol/L). But in FCS patients it rises up to 10 times than this level even with a low-fat diet or medication.
There are no effective therapies for the treatment of this condition. In an open-label study involving three FCS patients, antisense-mediated inhibition of hepatic APOC3 mRNA with volanesorsen led to decreased plasma apolipoprotein C-III and triglyceride levels.
Joseph L. Witztum, professor of medicine in the division of endocrinology and metabolism at the University of California San Diego School of Medicine, and colleagues conducted a phase 3, double-blind, randomized 52-week trial to evaluate the safety and effectiveness of volanesorsen in 66 patients with familial chylomicronemia syndrome.
Patients were randomly assigned to receive volanesorsen or placebo in the ratio of 1:1. Treatment was administered for 52 weeks. The primary endpoint was the percentage change in fasting triglyceride levels from baseline to 3 months.
Key findings include:
- Patients receiving volanesorsen had a decrease in mean plasma apolipoprotein C-III levels from baseline of 25.7 mg per deciliter, corresponding to an 84% decrease at 3 months, whereas patients receiving placebo had an increase in mean plasma apolipoprotein C-III levels from baseline of 1.9 mg per deciliter, corresponding to a 6.1% increase.
- Patients receiving volanesorsen had a 77% decrease in mean triglyceride levels, corresponding to a mean decrease of 1712 mg per deciliter (19.3 mmol per liter) (95% confidence interval [CI], 1330 to 2094 mg per deciliter [15.0 to 23.6 mmol per liter]), whereas patients receiving placebo had an 18% increase in mean triglyceride levels, corresponding to an increase of 92.0 mg per deciliter (1.0 mmol per liter) (95% CI, −301.0 to 486 mg per deciliter [–3.4 to 5.5 mmol per liter]) (P<0.001).
- At 3 months, 77% of the patients in the volanesorsen group, as compared with 10% of patients in the placebo group, had triglyceride levels of less than 750 mg per deciliter (8.5 mmol per liter).
- A total of 20 of 33 patients who received volanesorsen had injection-site reactions, whereas none of the patients who received placebo had such reactions.
- No patients in the placebo group had platelet counts below 100,000 per microliter, whereas 15 of 33 patients in the volanesorsen group had such levels, including 2 who had levels below 25,000 per microliter.
- No patient had platelet counts below 50,000 per microliter after enhanced platelet-monitoring began.
To sum up the findings volanesorsen lowered triglyceride levels to less than 750 mg per deciliter in 77% of patients with familial chylomicronemia syndrome.
To read the complete study log on to DOI: 10.1056/NEJMoa1715944