CAMBRIDGE, Mass.—Aegerion Pharmaceuticals is initiating Phase 3 trials in Japan for lomitapide, a drug that has already received regulatory approval in the United States, Canada, Mexico and the European Union. Lomitapide is used to treat homozygous familial hypercholesterolemia (HoFH), a rare inherited disease that causes severe hypercholesterolemia and greatly increases risk of premature coronary heart disease.
Aegerion, a biopharmaceutical company focused on developing treatments for debilitating rare diseases, has projected net sales of lomitapide, marketed as Juxtapid, between $180 million and $200 million in 2014. The company expects that Japan could become one of the top three markets for lomitapide, along with the United States and Brazil, if Japanese regulators approve the drug for marketing.
“This pivotal trial marks an important milestone for Aegerion and Japanese HoFH patients,” said Dr. Mark Sumeray, chief medical officer of Aegerion. “Japan is a well-characterized region for patients with severe hypercholesterolemia, and investigators there have shown a high level of enthusiasm for the trial, recognizing the unmet clinical need for their patients living with this serious disease.”
The open-label Phase 3 trial in Japan is similar in design to the completed Phase 3 trial conducted in the United States and other countries. Japan is the only market in which Aegerion is seeking approval for lomitapide that required the company to run a separate trial. The primary difference from earlier trials is its smaller size, with enrollment estimated between five and 10 patients. All of the patients will be adults with HoFH who are receiving concomitant lipid-lowering therapies, including, in some cases, apheresis.
Aegerion began patient enrollment for the Japanese trial in early April. The study will begin with a six-week run-in period, after which patients will receive lomitapide for 26 weeks, followed by a 30-week safety phase. During the 26-week efficacy phase of the study, dosages of lomitapide administered to patients will gradually increase, starting at 5 mg per day and escalating to a maximum dose of 60 mg based on tolerability.
Japan’s Pharmaceuticals and Medical Devices Agency has indicated it will allow Aegerion to file a new drug application following completion of the 26-week efficacy phase, which the company expects to occur during the middle of next year. Aegerion has already submitted regulatory filings for lomitapide in Brazil, Argentina, Israel and Taiwan based on the completed Phase 3 pivotal study. Last year, Aegerion received orphan drug designation from Japan’s Ministry of Health, Labour and Welfare for lomitapide. “Initiation of the Phase 3 trial in Japan allows us to sharpen focus on our regulatory timeline as we seek approval in this key market,” said Martha Carter, chief regulatory officer for Aegerion. “We currently hope to submit the filing for marketing approval in Japan as early as mid-2015.”
Lomitapide treats HoFH by reducing low-density lipoprotein cholesterol (LDL-C), commonly referred to as “bad cholesterol.” Reducing LDL-C is necessary because HoFH impairs the receptor responsible for removing it from the body, leading to a severe elevation of blood cholesterol levels. These high levels often result in HoFH patients developing premature and progressive atherosclerosis, which involves a narrowing or blocking of the arteries. Most individuals with HoFH have LDL cholesterol levels far higher than levels considered optimal by the American Heart Association.
The primary endpoint of Aegerion’s trial involves the percentage change in LDL-C levels that occurs in patients by the end of the 26-week efficacy phase. Secondary endpoints include the percentage change in lipid parameters, long-term safety and changes in hepatic fat that occur by week 56 of the trial.
