Lipid-efficacy RCT · Lancet 2013
Lomitapide phase 3 HoFH trial
Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study.
The bottom line
In patients with homozygous familial hypercholesterolaemia, lomitapide added to existing lipid-lowering therapy substantially lowered LDL cholesterol with durable effect through 78 weeks, though gastrointestinal side effects and reversible liver enzyme elevations were common.
Primary lipid endpoint metUS status: US-approved
At a glance
- Medicine
- Lomitapide, dose escalated from 5 mg to a maximum of 60 mg a day (median dose 40 mg a day), with current lipid lowering therapy maintained
- Compared with
- None (single-arm, baseline comparison)
- People
- 29
- Who took part
- Men and women aged 18 years or older with homozygous familial hypercholesterolaemia, recruited from 11 centres in four countries (USA, Canada, South Africa, and Italy)
- Design
- single-arm, open-label, phase 3 study
- Follow-up
- 26 weeks (efficacy phase); 78 weeks (full study, safety assessment)
- Main question
- Mean percent change in levels of LDL cholesterol from baseline to week 26
Main result
LDL cholesterol was reduced by 50% (95% CI -62 to -39) from baseline (mean 8·7 mmol/L [SD 2·9]) to week 26 (4·3 mmol/L [2·5]); p<0·0001
Effect on LDL cholesterol
Reduced by 50% (95% CI -62 to -39) at week 26; remained reduced by 44% (95% CI -57 to -31) at week 56 and 38% (-52 to -24) at week 78
Other results
Levels of LDL cholesterol were lower than 2·6 mmol/L in eight patients at 26 weeks
Safety
Gastrointestinal symptoms were the most common adverse event. Four patients had aminotransaminase levels of more than five times the upper limit of normal, which resolved after dose reduction or temporary interruption of lomitapide. No patient permanently discontinued treatment because of liver abnormalities.
In the trial's own words
“LDL cholesterol was reduced by 50% (95% CI -62 to -39) from baseline (mean 8·7 mmol/L [SD 2·9]) to week 26 (4·3 mmol/L [2·5]); p<0·0001). Levels of LDL cholesterol were lower than 2·6 mmol/L in eight patients at 26 weeks. Concentrations of LDL cholesterol remained reduced by 44% (95% CI -57 to -31; p<0·0001) at week 56 and 38% (-52 to -24; p<0·0001) at week 78.”
Quoted from the abstract of Lancet 2013, checked word for word against PubMed. PubMed 23122768 · Full paper (DOI)
How this medicine works, where it stands and what it costs: Lomitapide (Juxtapid)
Common questions
What did the Lomitapide phase 3 HoFH trial find?
In patients with homozygous familial hypercholesterolaemia, lomitapide added to existing lipid-lowering therapy substantially lowered LDL cholesterol with durable effect through 78 weeks, though gastrointestinal side effects and reversible liver enzyme elevations were common.
Who was in Lomitapide phase 3 HoFH?
29 people. Men and women aged 18 years or older with homozygous familial hypercholesterolaemia, recruited from 11 centres in four countries (USA, Canada, South Africa, and Italy).
What was Lomitapide phase 3 HoFH's main result?
LDL cholesterol was reduced by 50% (95% CI -62 to -39) from baseline (mean 8·7 mmol/L [SD 2·9]) to week 26 (4·3 mmol/L [2·5]); p<0·0001
How much did LDL cholesterol change in Lomitapide phase 3 HoFH?
Reduced by 50% (95% CI -62 to -39) at week 26; remained reduced by 44% (95% CI -57 to -31) at week 56 and 38% (-52 to -24) at week 78
Related trials
- APPROACH (2019)In patients with familial chylomicronemia syndrome, volanesorsen substantially lowered triglyceride and apolipoprotein C-III levels compared with placebo but caused frequent injection-site reactions and thrombocytopenia.
- ELIPSE HoFH (2020)In patients with homozygous familial hypercholesterolemia already on maximal lipid-lowering therapy, adding evinacumab markedly lowered LDL cholesterol compared with placebo, with similar adverse event rates.
- Evinacumab refractory HC (2020)In patients with refractory hypercholesterolemia despite maximal lipid-lowering therapy, evinacumab substantially and significantly lowered LDL cholesterol compared with placebo, with serious adverse events occurring at variable rates across dose groups.
- ARCHES-2 (2024)In adults with mixed hyperlipidemia, zodasiran (an RNAi therapy against ANGPTL3) produced significant, dose-dependent reductions in triglycerides and improvements in non-HDL-C, ApoB, and LDL-C compared with placebo, with a signal of transient HbA1c elevation in diabetic patients at the highest dose.
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