Assessment of efficacy and safety of volanesorsen for treatment of metabolic complications in patients with familial partial lipodystrophy: Results of the BROADEN study

Background: Volanesorsen, an antisense oligonucleotide, is designed to inhibit hepatic apolipopro-tein C-III synthesis and reduce plasma apolipoprotein C-III and triglyceride concentrations. Objective: The present study assessed efficacy and safety of volanesorsen in patients with familial partial lipodystrophy (FPLD) and concomitant hypertriglyceridemia and diabetes.Methods: BROADEN was a randomized, placebo-controlled, phase 2/3, 52-week study with open -label extension and post-treatment follow-up periods. Patients received weekly subcutaneous volane-sorsen 300 mg or placebo. The primary endpoint was percent change from baseline in fasting triglyc-erides at 3 months. Secondary endpoints included relative percent change in hepatic fat fraction (HFF), visceral adiposity, and glycated hemoglobin levels. Results: Forty patients (11 men, 29 women) were enrolled, majority of whom were aged < 65 years (mean, 47 years) and White. Least squares mean (LSM) percent change in triglycerides from baseline to 3 months was -88% (95% CI, -134 to -43) in the volanesorsen group versus -22% (95% CI, -61 to 18) in the placebo group, with a difference in LSM of -67% (95% CI, -104 to -30; P = 0.0009). Volanesorsen induced a significant LSM relative reduction in HFF of 53% at month 12 versus placebo (observed mean [SD]: 9.7 [7.65] vs. 18.0 [8.89]; P = 0.0039). No statistically significant changes were noted in body volume measurements (fat, liver, spleen, visceral/subcutaneous adipose tissue) or gly-cated hemoglobin. Serious adverse events in patients assigned to volanesorsen included 1 case each of sarcoidosis, anaphylactic reaction, and systemic inflammatory response syndrome.Conclusion: In BROADEN, volanesorsen significantly reduced serum triglyceride levels and hepatic steatosis in patients with FPLD.(c) 2022 Published by Elsevier Inc. on behalf of National Lipid Association.

Automated summary

The study evaluated the efficacy and safety of volanesorsen in patients with FPLD. The results showed that volanesorsen significantly reduced serum triglyceride levels and hepatic steatosis, but had no significant effects on body volume and glycated hemoglobin levels.