European approval for lomitapide to treat homozygous Familial Hypercholesterolemia (HoFH)
14/08/2013
Decision based on favorable benefit-risk assessment from phase 3 study on safety and efficacy to reduce LDL-C levels in adult patients with HoFH.
News - Aug. 15, 2013The European Commission has approved lomitapide (Aegerion Pharmaceuticals) 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 hypercholesterolemia (HoFH).
Lomitapide is indicated 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 hypercholesterolemia (HoFH). Genetic confirmation of HoFH should be obtained whenever possible, and other forms of primary hyperlipoproteinemia and secondary causes of hypercholesterolemia (e.g., nephrotic syndrome, hypothyroidism) must be excluded.
The European Commission's decision is based on a favorable benefit-risk assessment from a Phase 3 study 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, lomitapide significantly reduced LDL-C from a baseline average of 336 mg/dL to 190 mg/dL (40% reduction) at Week 26 in the intent-to-treat population. LDL-C was reduced by an average of 50% in the 23 patients who completed the study through Week 26. After Week 26, during the safety phase of the study, adjustments to concomitant lipid-lowering treatments, including apheresis, were allowed. Average reductions in LDL-C were sustained during chronic therapy and no additional dropouts were seen.
The most common adverse reactions in the Phase III trial were gastrointestinal, reported by 27 (93%) of 29 patients. Diarrhea 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. Ten 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 four 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.
According to Prof. Alberico L. Catapano, President of the European Atherosclerosis Society, patients with HoFH continue to experience severe elevations in LDL-C, despite the treatments available today. With novel therapies such as lomitapide it is possible to achieve target levels in LDL-C for patients with HoFH, which marks a change in the ability to truly impact the lives of these patients.
As part of Aegerion’s post-marketing commitment to both the FDA and the EMA, the company will conduct an observational cohort study to generate more data on the long-term safety profile of lomitapide, the patterns of use and compliance and the long-term effectiveness of controlling LDL-C levels.
Source
Press release Aegerion Pharmaceuticals
Lomitapide is indicated 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 hypercholesterolemia (HoFH). Genetic confirmation of HoFH should be obtained whenever possible, and other forms of primary hyperlipoproteinemia and secondary causes of hypercholesterolemia (e.g., nephrotic syndrome, hypothyroidism) must be excluded.
The European Commission's decision is based on a favorable benefit-risk assessment from a Phase 3 study 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, lomitapide significantly reduced LDL-C from a baseline average of 336 mg/dL to 190 mg/dL (40% reduction) at Week 26 in the intent-to-treat population. LDL-C was reduced by an average of 50% in the 23 patients who completed the study through Week 26. After Week 26, during the safety phase of the study, adjustments to concomitant lipid-lowering treatments, including apheresis, were allowed. Average reductions in LDL-C were sustained during chronic therapy and no additional dropouts were seen.
The most common adverse reactions in the Phase III trial were gastrointestinal, reported by 27 (93%) of 29 patients. Diarrhea 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. Ten 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 four 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.
According to Prof. Alberico L. Catapano, President of the European Atherosclerosis Society, patients with HoFH continue to experience severe elevations in LDL-C, despite the treatments available today. With novel therapies such as lomitapide it is possible to achieve target levels in LDL-C for patients with HoFH, which marks a change in the ability to truly impact the lives of these patients.
As part of Aegerion’s post-marketing commitment to both the FDA and the EMA, the company will conduct an observational cohort study to generate more data on the long-term safety profile of lomitapide, the patterns of use and compliance and the long-term effectiveness of controlling LDL-C levels.
Source
Press release Aegerion Pharmaceuticals