TY - JOUR
T1 - Assessment of efficacy and safety of volanesorsen for treatment of metabolic complications in patients with familial partial lipodystrophy
T2 - Results of the BROADEN study: Volanesorsen in FPLD; The BROADEN Study
AU - Oral, Elif A.
AU - Garg, Abhimanyu
AU - Tami, Joseph
AU - Huang, Eric A.
AU - O'Dea, Louis St L.
AU - Schmidt, Hartmut
AU - Tiulpakov, Anatoly
AU - Mertens, Ann
AU - Alexander, Veronica J.
AU - Watts, Lynnetta
AU - Hurh, Eunju
AU - Witztum, Joseph L.
AU - Geary, Richard S.
AU - Tsimikas, Sotirios
N1 - Funding Information:
This work was supported by Ionis Pharmaceuticals and Akcea Therapeutics. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Publisher Copyright:
© 2022
PY - 2022/11/1
Y1 - 2022/11/1
N2 - Background: Volanesorsen, an antisense oligonucleotide, is designed to inhibit hepatic apolipoprotein 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 volanesorsen 300 mg or placebo. The primary endpoint was percent change from baseline in fasting triglycerides 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 glycated 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.
AB - Background: Volanesorsen, an antisense oligonucleotide, is designed to inhibit hepatic apolipoprotein 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 volanesorsen 300 mg or placebo. The primary endpoint was percent change from baseline in fasting triglycerides 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 glycated 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.
KW - BROADEN
KW - Diabetes mellitus
KW - Familial partial lipodystrophy
KW - Hypertriglyceridemia
KW - Triglyceride
KW - Volanesorsen
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U2 - 10.1016/j.jacl.2022.08.008
DO - 10.1016/j.jacl.2022.08.008
M3 - Article
C2 - 36402670
AN - SCOPUS:85139341475
SN - 1933-2874
VL - 16
SP - 833
EP - 849
JO - Journal of Clinical Lipidology
JF - Journal of Clinical Lipidology
IS - 6
ER -