Date: 2015-11-10
Type of information: Presentation of results at a congress
phase:
Announcement: presentation of results at the 2015 American Heart Association's (AHA) Scientific Sessions in Orlando, Florida
Company: Aegerion Pharmaceuticals (USA - MA)
Product: lomitapide
Action
mechanism: protein inhibitor/microsomal triglyceride transfer protein (MTP) inhibitor. Lomitapide is a small molecule, microsomal triglyceride transfer protein inhibitor, or MTP-I. HoFH is a rare genetic disorder inherited from both parents, and characterised by significantly elevated low density lipoprotein cholesterol (LDL-C) levels. HoFH patients have LDL receptors that are either non-functional or are defective in their functioning. Patients diagnosed with HoFH typically have as much as three to six times the normal amount of LDL-C while on a variety of lipid-lowering drug treatments, putting them at risk for a major cardiovascular event. Most other drug treatments such as statins work by increasing the number of LDL-receptors and if these are defective or negative, the drugs that work by these mechanisms typically have limited effectiveness in HoFH patients. Inhibition of MTP reduces lipoprotein secretion and circulating concentrations of lipoprotein-borne lipids including cholesterol and triglycerides.
Disease: homozygous familial hypercholesterolemia
Therapeutic area: Rare diseases - Genetic diseases - Metabolic diseases
Country: USA
Trial
details: LOWER (Lomitapide Observational Worldwide Evaluation Registry) is a multicentre, long-term, prospective, observational cohort study (exposure registry), designed to evaluate the long term safety and effectiveness of lomitapide. (NCT02135705)
Latest
news: * On November 10, 2015, Aegerion Pharmaceuticals presented detailed one-year data from the Lomitapide Observational Worldwide Evaluation Registry (LOWER) study, which showed safety and efficacy results consistent with those observed in the pivotal study of lomitapide in adult patients with homozygous familial hypercholesterolemia (HoFH). There were no new safety signals. Lomitapide, marketed as Juxtapid® capsules in the U.S., is a microsomal triglyceride transfer protein inhibitor indicated in the U.S. as an adjunct to a low-fat diet and other lipid lowering treatments, including apheresis where available, to reduce low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), apolipoprotein B (apo B) and non-high-density lipoprotein cholesterol (non-HDL-C) in adult patients with HoFH. Lomitapide is also approved, with a comparable indication, under the brand name LOJUXTA® in the European Union.
LOWER is a global, long-term, prospective, observational registry of the long-term safety and effectiveness of lomitapide in clinical practice. These and future data from LOWER will provide further information about the long-term safety and effectiveness of lomitapide in a real world setting. At least 300 patients treated with lomitapide in a commercial setting will be followed for a minimum of 10 years. These data were presented in a poster entitled "Lomitapide Observational Worldwide Evaluation Registry (LOWER): One-Year Data" at the 2015 American Heart Association's (AHA) Scientific Sessions in Orlando, Florida. As of March 1, 2015, 84 patients with mean age 55.4 (SD 11.5) years, were enrolled in LOWER; 6 (7%) have since discontinued. Exposure duration was up to 26 months, with 60% of patients receiving the drug for ? 12 months. Lomitapide dose ranged from 5 to 40 mg; dose increased over time to a median of 13.0 mg (mean 14.4 mg) after 2 years' exposure. Mean LDL-C at baseline was 216.3 (SD 76.9) mg/dL which decreased by 42% at Month 4 and was maintained throughout the reporting period. Fifty-one (61%) and 30 (36%) patients, respectively, achieved an LDL-C value < 100 mg/dL or <70 mg/dL, at least once while receiving lomitapide. Events of special interest (ESI) include: 1 major adverse cardiovascular event (MACE) resulting in death; 11 hepatic events; and 6 gastrointestinal events. No tumors, pregnancies, or coagulopathy events were reported. Elevated aminotransferase levels ?3x upper limit of normal (ULN) were observed in 16 patients (20%); 4 of these patients experienced elevations of ?5x - <10x ULN. No cases of Hy's Law were recorded. Diarrhea was the most common adverse event (AE), experienced by 24% of patients, and was the only AE reported by > 10% of patients. Serious AEs occurred in 6 (7%) patients. Eight (10%) patients discontinued lomitapide because of an AE.
Data from this first LOWER annual report also indicate that in the US, prescribers are not consistently following liver monitoring guidelines outlined in the prescribing information for Juxtapid or administering pregnancy tests prior to initiating treatment with Juxtapid®.
