European Commission authorisation comes approximately two months after positive CHMP opinion
Aegerion Pharmaceuticals, Inc. (NASDAQ: AEGR), a biopharmaceutical company dedicated to the development and commercialisation of novel, life-altering therapies for patients with debilitating, often fatal, rare diseases, announced today that the European Commission has authorised Lojuxta™ (lomitapide) hard capsules as an adjunct to a low-fat diet and other lipid-lowering medicinal products with or without low density lipoprotein (LDL) apheresis in adult patients with homozygous familial hypercholesterolaemia (HoFH).
HoFH is a life threatening, rare inherited disease affecting an estimated one person per million population. Patients with HoFH have impaired function of the receptor responsible for removing LDL-C (“bad” cholesterol) from the body. This loss of LDL receptor function results in extreme elevations of blood cholesterol levels with HoFH patients developing premature and progressive atherosclerosis (a narrowing or blocking of the arteries), symptoms of cardiovascular disease (CVD) at an early age and a significantly reduced life expectancy.
Jules Payne, Chief Executive of HEART UK, the Cholesterol Charity, said, “Up to now, the impact of this rare disease has meant that patients with HoFH live with premature CVD symptoms, surgical intervention by their early 20s and the threat of an early death. Furthermore in the UK, specialist treatments such as LDL-apheresis, the current standard of care can be difficult to access with only 8 centres currently offering this treatment. Therefore the marketing authorisation of Lojuxta, an oral medicine, brings hope that HoFH can now be managed more effectively.”
Professor Gilbert Thompson, Emeritus Professor of Clinical Lipidology, Imperial College London, commented, “There is a significant unmet need as patients with HoFH respond inadequately to existing therapies. Even with weekly lipoprotein apheresis and maximal tolerable doses of statins plus other cholesterol lowering drugs, such as ezetimibe, the levels of LDL-C we are able to achieve will probably only postpone rather than prevent CV disease in most instances. Treatment with lomitapide could be of real benefit in the management of HoFH, substantially reducing levels of LDL-C and making a tangible difference to what we are currently able to achieve.”
The European Commission's decision is based on positive findings from Aegerion’s Phase 3 study, published in the Lancet, which evaluated the safety and efficacy of the medicine to reduce LDL-C levels in 29 adult patients with HoFH. When added to the existing lipid-lowering therapy of the HoFH patients in the study, Lojuxta significantly reduced LDL-C from a baseline average of 8.7 mmol/L to 4.9 mmol/L (40% reduction) at Week 26 in the intent-to-treat population with last observation carried forward for the patients who discontinued prematurely. LDL-C was reduced by an average of 50% from 8.7 mmol/L to 4.3 mmol/L for the 23 patients who completed the study through Week 26. After Week 26, during the safety phase of the study lasting an additional 52 weeks, adjustments to concomitant lipid-lowering treatments, including apheresis, were allowed. Average reductions in LDL-C were sustained over the 52-weeks and no further patients discontinued from the study. During this period, of the 13 patients on apheresis, 6 (23%) were able to stop apheresis, at the clinician’s discretion and for a further 6 (23%) patients, the frequency of apheresis sessions was decreased. In addition, 16 subjects achieved the critical LDL-C target levels as defined by the European Atherosclerosis Society/European Society of Cardiology of < 2.6 mmol/L (< 100mg/dl) for patients with high risk of CV disease and of these 9 achieved levels < 1.8 mmol/L (< 70mg/dl) for patients at very high risk of CV disease at any time throughout the study. At entry to the study none of the 29 patients were able to achieve these levels on maximal tolerated lipid lowering therapies, with or without apheresis.
The most common adverse reactions in the Phase 3 trial were gastrointestinal, reported by 27 (93%) of 29 patients. Diarrhoea occurred in 79% of patients, nausea in 65%, dyspepsia in 38%, and vomiting in 34%. Other reactions reported by at least 20% of patients include abdominal pain, abdominal discomfort, abdominal distension, constipation, and flatulence. Elevations in liver enzymes and hepatic (liver) fat were also observed. 10 of the 29 patients in the study had at least one elevation in liver enzymes greater than or equal to three times the upper limit of normal, including 4 patients who experienced liver enzymes greater than or equal to five times the upper limit of normal. Liver enzyme elevations were managed through dose reduction or temporary discontinuation of dose. There were no clinically meaningful elevations of total bilirubin, international normalized ratio (INR) or alkaline phosphatase, which are other markers of potential harmful effects on the liver. Hepatic fat increased from a baseline of one percent to a median absolute increase of six percent at 26 and 78 weeks.