Homozygous familial hypercholesterolemia is a rare genetic condition that is often characterized by an increased risk of premature cardiovascular (CV) events and cardiac death. Lomitapide decreases low-density lipoprotein cholesterol (LDL-C) levels, but there is little research of the effects on LDL-C goals and CV events.
Homozygous familial hypercholesterolemia (HoFH) is a rare genetic condition that is often characterized by an increased risk of premature cardiovascular (CV) events and cardiac death. Lomitapide decreases low-density lipoprotein cholesterol (LDL-C) levels, but there is little research of the effects on LDL-C goals and CV events.
In a recent study in Orphanet Journal of Rare Diseases, researchers collected data during the first 26 weeks of the lomitapide pivotal phase 3 study (NCT00730236) in order to assess the achievements of European Atherosclerosis Society (EAS) LDL-C targets. Additionally, data of major adverse CV events (MACE) rates were collected from other cohorts of patients with HoFH—treated with mipomersen and evolocumab—in order to compare event rates.
“Lomitapide is an oral microsomal triglyceride transfer protein inhibitor that reduces the assembly of lipoproteins containing apolipoprotein B in the intestine and liver, and therefore does not require functioning LDL-receptors to lower LDL-C levels,” explained the researchers. “Lomitapide was approved as adjunctive therapy in adult patients with HoFH following a small open-label single-arm phase 3 study.”
In total, 29 patients were included in the study. During the first 26 weeks, the researchers found that 15 (51%) reached LDL-C targets of 100 mg/dL and 8 (28%) reached 70 mg/dL, at least once. Also, 14 (74%) and 11 (58%) of the 19 patients who remained for the extension study after week 126 reached LDL-C targets of 100 mg/dL and 70 mg/dL at least once during the study period.
Furthermore, only 2 MACE were reported in the lomitapide trials: a cardiac death and a coronary artery bypass graft. Overall the MACE rates were 21.7, 9.5 and 1.8 per 1000 patient-months respectively in cohorts of patients with HoFH pre- and postmipomersen, and receiving evolocumab, according to the researchers. On treatment, the LDL-C levels were 166 mg/dL for lomitapide, 331 mg/dL for mipomersen, and 286 mg/dL for evoloccumab.
“There were fewer major CV events per 1000 patient months of treatment in patients taking lomitapide, mipomersen, or evolocumab than reported in the mipomersen cohort prior to starting mipomersen,” the study concluded. “These results support the hypothesis that novel lipid-lowering therapies may reduce CV events in HoFH patients by lowering LDL-C further.”
The study was limited because the MACE rate comparison included in the lomitapide studies were open-label and did not include a control group that was receiving a placebo. Also, the mipomersen and evolocumab studies did not include placebos of sufficient duration in order to evaluate the CV event rates.
The researchers emphasized that these results reveal that lomitapide and other novel lipid-lowering therapy may lead to improvements in the prognosis of patients with HoFH.
Blom DJ, Cuchel M, Ager M, Phillips H. Target achievement and cardiovascular event rates with lomitapide in homozygous familial hypercholesterolaemia. Orphanet J Rare Dis. 2018;13:96. doi: 10.1186/s13023-018-0841-3.