Briefing Docs on Lomitapide Favorable; Aegerion's Stock up
By Peter Winter
Editor, BioWorld Insight
Cholesterol-lowering drug candidates are in the spotlight this week with the FDA's Endocrinologic and Metabolic Drugs Advisory Committee (EMDAC) meeting Wednesday and Thursday to pass judgment on two of those drugs lomitapide from Aegerion Pharmaceuticals Inc.; and Kynamro (mipomersen sodium) from Genzyme, a unit of Sanofi SA, a first-in-class second-generation antisense apolipoprotein B synthesis inhibitor, developed by Isis Pharmaceuticals Inc.
Both target the same indication homozygous familial hypercholesterolemia (HoFH), a rare and generally fatal disease, but each has a different mechanism of action.
EMDAC will review lomitapide, a once-a-day oral therapeutic on Oct. 17. The drug is a microsomal triglyceride transfer protein inhibitor (MTP-I), a new class of cholesterol- and triglyceride-lowering agents designed to work by preventing the liver and intestines from secreting lipids into the bloodstream, thereby reducing those levels.
According to Robyn Karnauskas, analyst at Deutsche Bank, the briefing documents released ahead of the meeting suggested that approval be granted with no major "red flags" on the drug's safety profile.
Commenting on the company's proposed risk evaluation and mitigation strategy (REMS), the FDA said in the briefing documents that it would support appropriate use of lomitapide, allowing it to be approved for use in the targeted patient population, one that currently has limited therapeutic options. "We believe that the proposed REMS is needed to ensure that the benefits of lomitapide outweigh the potential risk of serious liver injury."
EMDAC will be reviewing the results from Aegerion's pivotal Phase III study that evaluated the safety and efficacy of lomitapide as an adjunct to a low-fat diet and other lipid-lowering therapies to reduce LDL-C levels in HoFH patients. In all, 29 subjects were exposed to lomitapide, with 23 exposed for at least one year, 15 for at least two years and five for at least three years.
Those patients were maintained on current lipid-lowering therapy from six weeks prior to baseline. The lomitapide dose was escalated from 5 mg to a maximum-tolerated dose of up to 60 mg/day. The primary efficacy endpoint was mean percentage change in LDL-C from baseline at week 26, after which patients remained on lomitapide for safety follow-up through to week 78.
The data demonstrated that the reduction in LDL-C cholesterol from baseline was maintained at 78-weeks and consistent with the 56-week data, which showed that patients had a 44 percent reduction in LDL cholesterol levels from baseline and a 33.3 percent reduction in triglyceride levels. (See BioWorld Today, June 27, 2011.)
Severe hypercholesterolemia is characterized by very high levels of cholesterol in the blood, which is known to increase the risk of coronary artery disease. Most forms of hypercholesterolemia can be treated through lifestyle modifications, but a large proportion of patients with hypercholesterolemia are not achieving target LDL-C goals with statin therapy, including genetic familial hypercholesterolemia patients. (See BioWorld Insight, Sept. 24, 2012.)
Lomitapide was granted orphan drug designation by the FDA in HoFH and and familial chylomicronemia (FC), and by the European Medicines Agency (EMA) in FC.
The FDA is scheduled to make a final decision on lomitapide by the end of the year.
Based on the favorable opinions from the briefing documents, shares of Aegerion (NASDAQ:AEGR) closed Monday at $17.46, up 9.4 percent, or $1.50, in heavy market trading that was 10 times higher than the average volume.
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