CAMBRIDGE, Mass., Nov. 10, 2015 (GLOBE NEWSWIRE) -- Aegerion Pharmaceuticals, Inc. (NASDAQ:AEGR), a biopharmaceutical company dedicated to the development and commercialization of innovative therapies for patients with debilitating rare diseases, today presented detailed one-year data from the Company’s 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.
Mark Sumeray, MD, Chief Medical Officer of Aegerion commented, “These new lomitapide data continue to show consistent and clinically meaningful efficacy in patients diagnosed with HoFH. In addition, the safety and tolerability of lomitapide appears consistent with the Phase 3 study that was the basis for JUXTAPID approval from the US Food and Drug Administration and other approvals of lomitapide globally.”
About the One-Year LOWER Data
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.
About HoFH
HoFH is a serious, rare genetic disease inherited from both parents that impairs the function of the receptor responsible for removing low-density lipoprotein cholesterol (LDL-C or "bad" cholesterol) from the body. A loss of LDL receptor function results in extreme elevation of blood cholesterol levels. HoFH patients often develop premature and progressive atherosclerosis, a narrowing or blocking of the arteries.
About Lomitapide
Lomitapide, marketed as JUXTAPID® in the U.S., and LOJUXTA® in the EU, is a microsomal triglyceride transfer protein (MTP) inhibitor that works independently of LDL receptor functionality. JUXTAPID is indicated in the United States as an adjunct to a low-fat diet and other lipid-lowering treatments, including LDL 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 patients with homozygous familial hypercholesterolemia (HoFH). The safety and effectiveness of lomitapide have not been established in patients with hypercholesterolemia who do not have HoFH. The effect of lomitapide on cardiovascular morbidity and mortality has not been determined.
Important Safety Information, including BOXED WARNING which states: WARNING: RISK OF HEPATOTOXICITY
JUXTAPID can cause elevations in transaminases. In the JUXTAPID clinical trial, 10 (34%) of the 29 patients treated with JUXTAPID had at least one elevation in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3x upper limit of normal (ULN). There were no concomitant clinically meaningful elevations of total bilirubin, international normalized ratio (INR), or alkaline phosphatase.
JUXTAPID also increases hepatic fat, with or without concomitant increases in transaminases. The median absolute increase in hepatic fat was 6% after both 26 and 78 weeks of treatment, from 1% at baseline, measured by magnetic resonance spectroscopy. Hepatic steatosis associated with JUXTAPID treatment may be a risk factor for progressive liver disease, including steatohepatitis and cirrhosis.
Measure ALT, AST, alkaline phosphatase, and total bilirubin before initiating treatment and then ALT and AST regularly as recommended. During treatment, adjust the dose of JUXTAPID if the ALT or AST are ≥3x ULN. Discontinue JUXTAPID for clinically significant liver toxicity.
Because of the risk of hepatotoxicity, JUXTAPID is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the JUXTAPID REMS PROGRAM.
CONTRAINDICATIONS
- Pregnancy
- Concomitant administration of moderate or strong CYP3A4 inhibitors
- Moderate or severe hepatic impairment or active liver disease including unexplained persistent elevations of serum transaminases
WARNINGS AND PRECAUTIONS
JUXTAPID can cause elevations in transaminases and hepatic steatosis. Although cases of hepatic failure have not been reported, there is concern that JUXTAPID could induce steatohepatitis, which can progress to cirrhosis over several years. Modify the dose of JUXTAPID if elevations of transaminases are observed and discontinue JUXTAPID for persistent or clinically significant elevations. If transaminase elevations are accompanied by clinical symptoms of liver injury, such as nausea, vomiting, abdominal pain, fever, jaundice, lethargy, flu-like-symptoms, increases in bilirubin ≥2x ULN, or active liver disease, discontinue treatment with JUXTAPID and identify the probable cause. Use JUXTAPID with caution when co-administered with agents known to be hepatotoxic. Alcohol may increase levels of hepatic fat and induce or exacerbate liver injury.
Measure ALT, AST, alkaline phosphatase, and total bilirubin before initiating treatment. During the first year, measure liver-related tests (ALT and AST, at a minimum) prior to each increase in dose or monthly, whichever occurs first. After the first year, do these tests at least every 3 months and before any increase in dose.
Females of reproductive potential should have a negative pregnancy test before starting JUXTAPID and should use effective contraception during therapy with JUXTAPID.
Given its mechanism of action in the small intestine, JUXTAPID may reduce the absorption of fat-soluble nutrients. Patients treated with JUXTAPID should take daily supplements that contain 400 international units vitamin E and at least 200 mg linoleic acid, 210 mg alpha-linolenic acid (ALA), 110 mg eicosapentaenoic acid (EPA), and 80 mg docosahexaenoic acid (DHA).
Gastrointestinal adverse reactions are common and may lead to treatment discontinuation. To reduce the risk of gastrointestinal adverse reactions, patients should adhere to a low-fat diet supplying less than 20% of energy from fat and the dosage of JUXTAPID should be increased gradually.
Combination with CYP3A4 inhibitors increases exposure to lomitapide. Strong and moderate CYP3A4 inhibitors should not be used with JUXTAPID. JUXTAPID dosage should not exceed 30 mg daily when used concomitantly with weak CYP3A4 inhibitors.
Due to risk of myopathy associated with simvastatin or lovastatin, doses of these agents should be limited when co-administered with JUXTAPID.
JUXTAPID increases the plasma concentrations of warfarin. Increases or decreases in the dose of JUXTAPID may lead to supra- or subtherapeutic anticoagulation, respectively. Patients taking warfarin should undergo regular monitoring of the INR, especially after any changes in JUXTAPID dosage.
Avoid use of JUXTAPID in patients with rare hereditary disorders of galactose intolerance.
ADVERSE REACTIONS
The most common adverse reactions were gastrointestinal, reported by 27 (93%) of 29 patients. Adverse reactions reported by ≥8 (28%) or more patients in the HoFH clinical trial included diarrhea, nausea, vomiting, dyspepsia and abdominal pain. Other common adverse reactions, reported by 5 to 7 (17-24%) patients, included weight loss, abdominal discomfort, abdominal distension, constipation, flatulence, increased ALT, chest pain, influenza, nasopharyngitis, and fatigue.
About Aegerion Pharmaceuticals, Inc.
Aegerion Pharmaceuticals is a biopharmaceutical company dedicated to the development and commercialization of innovative therapies for patients with debilitating rare diseases. For more information about the company, please visit www.aegerion.com.