Long-term efficacy and safety of mipomersen in patients with familial hypercholesterolaemia: 2-year interim results of an open-label extension

Raul D. Santos, Paul Duell, Cara East, John R. Guyton, Patrick M. Moriarty, Wai Chin, Robert S. Mittleman

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

Aims To evaluate the efficacy and safety of extended dosing with mipomersen in patients with familial hypercholesterolaemia (HC) taking maximally tolerated lipid-lowering therapy. Methods and results A planned interim analysis of an ongoing, open-label extension trial in patients (n ≥ 141) with familial HC receiving a subcutaneous injection of 200 mg mipomersen weekly plus maximally tolerated lipid-lowering therapy for up to 104 weeks. The mean changes in low-density lipoprotein cholesterol (LDL-C) from baseline to weeks 26 (n ≥ 130), 52 (n ≥ 111), 76 (n ≥ 66), and 104 (n ≥ 53) were -28, -27, -27, and -28%; and in apolipoprotein B -29, -28, -30, and -31%, respectively. Reductions in total cholesterol, non-high-density lipoprotein-cholesterol, and lipoprotein(a) were comparable with decreases in LDL-C and apolipoprotein B levels. Mean high-density lipoprotein cholesterol increased from baseline by 7 and 6% at weeks 26 and 52, respectively. The long-term safety profile of mipomersen was similar to that reported in the associated randomized placebo-controlled Phase 3 trials. Adverse events included injection site reactions and flu-like symptoms. There was an incremental increase in the median liver fat during the initial 6-12 months that appeared to diminish with continued mipomersen exposure beyond 1 year and returned towards baseline 24 weeks after last drug dose suggestive of adaptation. The median alanine aminotransferase level showed a similar trend over time. Conclusion Long-term treatment with mipomersen for up to 104 weeks provided sustained reductions in all atherosclerotic lipoproteins measured and a safety profile consistent with prior controlled trials in these high-risk patient populations.

Original languageEnglish (US)
Pages (from-to)566-575
Number of pages10
JournalEuropean Heart Journal
Volume36
Issue number9
DOIs
StatePublished - Mar 1 2015

Fingerprint

Hyperlipoproteinemia Type II
Safety
Apolipoproteins B
LDL Cholesterol
Lipids
Lipoprotein(a)
Subcutaneous Injections
Alanine Transaminase
HDL Cholesterol
Lipoproteins
Therapeutics
Fats
Cholesterol
Placebos
mipomersen
Injections
Liver
Pharmaceutical Preparations
Population

Keywords

  • Adverse events
  • Familial hypercholesterolaemia
  • Hypercholesterolaemia
  • Lipid-lowering
  • Long-term safety

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Long-term efficacy and safety of mipomersen in patients with familial hypercholesterolaemia : 2-year interim results of an open-label extension. / Santos, Raul D.; Duell, Paul; East, Cara; Guyton, John R.; Moriarty, Patrick M.; Chin, Wai; Mittleman, Robert S.

In: European Heart Journal, Vol. 36, No. 9, 01.03.2015, p. 566-575.

Research output: Contribution to journalArticle

Santos, Raul D. ; Duell, Paul ; East, Cara ; Guyton, John R. ; Moriarty, Patrick M. ; Chin, Wai ; Mittleman, Robert S. / Long-term efficacy and safety of mipomersen in patients with familial hypercholesterolaemia : 2-year interim results of an open-label extension. In: European Heart Journal. 2015 ; Vol. 36, No. 9. pp. 566-575.
@article{43d4a0aa7b4a44d39365fc56a2d9ff60,
title = "Long-term efficacy and safety of mipomersen in patients with familial hypercholesterolaemia: 2-year interim results of an open-label extension",
abstract = "Aims To evaluate the efficacy and safety of extended dosing with mipomersen in patients with familial hypercholesterolaemia (HC) taking maximally tolerated lipid-lowering therapy. Methods and results A planned interim analysis of an ongoing, open-label extension trial in patients (n ≥ 141) with familial HC receiving a subcutaneous injection of 200 mg mipomersen weekly plus maximally tolerated lipid-lowering therapy for up to 104 weeks. The mean changes in low-density lipoprotein cholesterol (LDL-C) from baseline to weeks 26 (n ≥ 130), 52 (n ≥ 111), 76 (n ≥ 66), and 104 (n ≥ 53) were -28, -27, -27, and -28{\%}; and in apolipoprotein B -29, -28, -30, and -31{\%}, respectively. Reductions in total cholesterol, non-high-density lipoprotein-cholesterol, and lipoprotein(a) were comparable with decreases in LDL-C and apolipoprotein B levels. Mean high-density lipoprotein cholesterol increased from baseline by 7 and 6{\%} at weeks 26 and 52, respectively. The long-term safety profile of mipomersen was similar to that reported in the associated randomized placebo-controlled Phase 3 trials. Adverse events included injection site reactions and flu-like symptoms. There was an incremental increase in the median liver fat during the initial 6-12 months that appeared to diminish with continued mipomersen exposure beyond 1 year and returned towards baseline 24 weeks after last drug dose suggestive of adaptation. The median alanine aminotransferase level showed a similar trend over time. Conclusion Long-term treatment with mipomersen for up to 104 weeks provided sustained reductions in all atherosclerotic lipoproteins measured and a safety profile consistent with prior controlled trials in these high-risk patient populations.",
keywords = "Adverse events, Familial hypercholesterolaemia, Hypercholesterolaemia, Lipid-lowering, Long-term safety",
author = "Santos, {Raul D.} and Paul Duell and Cara East and Guyton, {John R.} and Moriarty, {Patrick M.} and Wai Chin and Mittleman, {Robert S.}",
year = "2015",
month = "3",
day = "1",
doi = "10.1093/eurheartj/eht549",
language = "English (US)",
volume = "36",
pages = "566--575",
journal = "European Heart Journal",
issn = "0195-668X",
publisher = "Oxford University Press",
number = "9",

}

TY - JOUR

T1 - Long-term efficacy and safety of mipomersen in patients with familial hypercholesterolaemia

T2 - 2-year interim results of an open-label extension

AU - Santos, Raul D.

AU - Duell, Paul

AU - East, Cara

AU - Guyton, John R.

AU - Moriarty, Patrick M.

AU - Chin, Wai

AU - Mittleman, Robert S.

PY - 2015/3/1

Y1 - 2015/3/1

N2 - Aims To evaluate the efficacy and safety of extended dosing with mipomersen in patients with familial hypercholesterolaemia (HC) taking maximally tolerated lipid-lowering therapy. Methods and results A planned interim analysis of an ongoing, open-label extension trial in patients (n ≥ 141) with familial HC receiving a subcutaneous injection of 200 mg mipomersen weekly plus maximally tolerated lipid-lowering therapy for up to 104 weeks. The mean changes in low-density lipoprotein cholesterol (LDL-C) from baseline to weeks 26 (n ≥ 130), 52 (n ≥ 111), 76 (n ≥ 66), and 104 (n ≥ 53) were -28, -27, -27, and -28%; and in apolipoprotein B -29, -28, -30, and -31%, respectively. Reductions in total cholesterol, non-high-density lipoprotein-cholesterol, and lipoprotein(a) were comparable with decreases in LDL-C and apolipoprotein B levels. Mean high-density lipoprotein cholesterol increased from baseline by 7 and 6% at weeks 26 and 52, respectively. The long-term safety profile of mipomersen was similar to that reported in the associated randomized placebo-controlled Phase 3 trials. Adverse events included injection site reactions and flu-like symptoms. There was an incremental increase in the median liver fat during the initial 6-12 months that appeared to diminish with continued mipomersen exposure beyond 1 year and returned towards baseline 24 weeks after last drug dose suggestive of adaptation. The median alanine aminotransferase level showed a similar trend over time. Conclusion Long-term treatment with mipomersen for up to 104 weeks provided sustained reductions in all atherosclerotic lipoproteins measured and a safety profile consistent with prior controlled trials in these high-risk patient populations.

AB - Aims To evaluate the efficacy and safety of extended dosing with mipomersen in patients with familial hypercholesterolaemia (HC) taking maximally tolerated lipid-lowering therapy. Methods and results A planned interim analysis of an ongoing, open-label extension trial in patients (n ≥ 141) with familial HC receiving a subcutaneous injection of 200 mg mipomersen weekly plus maximally tolerated lipid-lowering therapy for up to 104 weeks. The mean changes in low-density lipoprotein cholesterol (LDL-C) from baseline to weeks 26 (n ≥ 130), 52 (n ≥ 111), 76 (n ≥ 66), and 104 (n ≥ 53) were -28, -27, -27, and -28%; and in apolipoprotein B -29, -28, -30, and -31%, respectively. Reductions in total cholesterol, non-high-density lipoprotein-cholesterol, and lipoprotein(a) were comparable with decreases in LDL-C and apolipoprotein B levels. Mean high-density lipoprotein cholesterol increased from baseline by 7 and 6% at weeks 26 and 52, respectively. The long-term safety profile of mipomersen was similar to that reported in the associated randomized placebo-controlled Phase 3 trials. Adverse events included injection site reactions and flu-like symptoms. There was an incremental increase in the median liver fat during the initial 6-12 months that appeared to diminish with continued mipomersen exposure beyond 1 year and returned towards baseline 24 weeks after last drug dose suggestive of adaptation. The median alanine aminotransferase level showed a similar trend over time. Conclusion Long-term treatment with mipomersen for up to 104 weeks provided sustained reductions in all atherosclerotic lipoproteins measured and a safety profile consistent with prior controlled trials in these high-risk patient populations.

KW - Adverse events

KW - Familial hypercholesterolaemia

KW - Hypercholesterolaemia

KW - Lipid-lowering

KW - Long-term safety

UR - http://www.scopus.com/inward/record.url?scp=84924415690&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84924415690&partnerID=8YFLogxK

U2 - 10.1093/eurheartj/eht549

DO - 10.1093/eurheartj/eht549

M3 - Article

C2 - 24366918

AN - SCOPUS:84924415690

VL - 36

SP - 566

EP - 575

JO - European Heart Journal

JF - European Heart Journal

SN - 0195-668X

IS - 9

ER -