Atherosclerosis · 2025
Effect of olezarsen on lipoprotein-associated ApoC-III levels in patients with familial chylomicronemia syndrome.
Клиническое исследование III фазыСтатьяРандомизированное исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Yang Xiaohong, Alexander Veronica J, Xia Shuting, Tsimikas Sotirios
Аннотация
BACKGROUND: Apolipoprotein C-III (apoC-III) is transported on chylomicrons, very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL) and lipoprotein(a) [Lp(a)]. Olezarsen, a hepatic-targeted antisense oligonucleotide targeting APOC3 mRNA, lowers apoC-III and triglycerides and reduces pancreatitis events. This study evaluated the reduction of apoC-III in specific lipoprotein pools after treatment with olezarsen.
METHODS: Participants with familial chylomicronemia syndrome (FCS) in the Balance study received olezarsen 80 mg (n = 22), 50 mg (n = 21), or placebo (n = 23). Triglycerides, apoC-III, and lipoprotein-associated apoC-III was measured at baseline and days 85, 169, 253, and 365 using chemiluminescent ELISAs. Lipoprotein-associated apoC-III levels were measured in 4 lipoprotein pools, apoC-III-total apoB (apoB-48+apoB-100), apoC-III-apoA-I (HDL), apoC-III-apoB-100 (VLDL + LDL), and apoC-III-apo(a) (Lp(a)). The placebo-adjusted average percent changes from baseline to day 365 were calculated.
RESULTS: The average percent changes from baseline to day 365 in apoC-III were -61.9 % and -74.7 % and for triglycerides -37.8 % and -55.7 % with olezarsen 50 mg and olezarsen 80 mg, respectively. The corresponding olezarsen-placebo average differences (95 % CI) in apoC-III-total apoB levels were -47.1 % (-64.1, -32.6) and -65.8 % (-81.5, -49.8), respectively and apoC-III-apoA-I by -53.6 % (-79.3, -29.4) and -76.1 % (-104.1, -55.4), respectively (p<0.001 for all). ApoC-III-apoB-100 was reduced by -12.5 % (-28.1, 2.1) (p = 0.0768) and -29.9 % (-46.1, -16.0) (p = 0.0006) and apoC-III-apo(a) by -15.7 % (-47.5, 10.6) (p = 0.18) and -39.1 % (-70.2, -16.1) (p = 0.0024), with olezarsen 50 mg and olezarsen 80 mg respectively.
CONCLUSIONS: In adults with FCS, olezarsen significantly lowers apoC-III in all major lipoprotein pools, particularly in total apoB and apoA-I. Tracking changes in apoC-III among various lipoprotein pools elucidates the action of olezarsen on apoC-III and may inform future studies of pancreatitis and cardiovascular risk with apoC-III-targeted therapies.
METHODS: Participants with familial chylomicronemia syndrome (FCS) in the Balance study received olezarsen 80 mg (n = 22), 50 mg (n = 21), or placebo (n = 23). Triglycerides, apoC-III, and lipoprotein-associated apoC-III was measured at baseline and days 85, 169, 253, and 365 using chemiluminescent ELISAs. Lipoprotein-associated apoC-III levels were measured in 4 lipoprotein pools, apoC-III-total apoB (apoB-48+apoB-100), apoC-III-apoA-I (HDL), apoC-III-apoB-100 (VLDL + LDL), and apoC-III-apo(a) (Lp(a)). The placebo-adjusted average percent changes from baseline to day 365 were calculated.
RESULTS: The average percent changes from baseline to day 365 in apoC-III were -61.9 % and -74.7 % and for triglycerides -37.8 % and -55.7 % with olezarsen 50 mg and olezarsen 80 mg, respectively. The corresponding olezarsen-placebo average differences (95 % CI) in apoC-III-total apoB levels were -47.1 % (-64.1, -32.6) and -65.8 % (-81.5, -49.8), respectively and apoC-III-apoA-I by -53.6 % (-79.3, -29.4) and -76.1 % (-104.1, -55.4), respectively (p<0.001 for all). ApoC-III-apoB-100 was reduced by -12.5 % (-28.1, 2.1) (p = 0.0768) and -29.9 % (-46.1, -16.0) (p = 0.0006) and apoC-III-apo(a) by -15.7 % (-47.5, 10.6) (p = 0.18) and -39.1 % (-70.2, -16.1) (p = 0.0024), with olezarsen 50 mg and olezarsen 80 mg respectively.
CONCLUSIONS: In adults with FCS, olezarsen significantly lowers apoC-III in all major lipoprotein pools, particularly in total apoB and apoA-I. Tracking changes in apoC-III among various lipoprotein pools elucidates the action of olezarsen on apoC-III and may inform future studies of pancreatitis and cardiovascular risk with apoC-III-targeted therapies.