Novelion Therapeutics announced that subsidiary Aegerion Pharmaceuticals completed the first commercial shipment of Juxtapid (lomitapide) to a patient in Japan. In September 2016, Juxtapid was approved by Japan's Ministry of Health, Labor & Welfare (MHLW) for patients with homozygous familial hypercholesterolemia (HoFH).
Mary Szela, chief executive officer of Novelion said, "Japan is an important market and we are pleased to be able to provide this needed therapy to HoFH patients there shortly following the recent approval. Japan is unique in that there is a well-defined population of over 160 HoFH patients at last count registered with the Intractable Diseases Information Center. We are working closely with Japanese healthcare providers to identify those patients appropriate for JUXTAPID therapy, and following the recent approval of pricing and reimbursement in line with our expectations, we are working to bring HoFH patients in need onto therapy."
HoFH is a serious, rare genetic disease that impairs the function of the receptor responsible for removing LDL-C (bad cholesterol) from the body. A loss of LDL receptor function results in extreme evaluation of blood cholesterol levels. HoFH patients often develop premature and progressive atherosclerosis, a narrowing or blocking of the arteries.
The MHLW based its approval of Juxtapid on Aegerion's phase III study in Japanese patients, which evaluated the safety and efficacy of the medicine to reduce LDL-C levels in nine patients with HoFH. The findings were consistent with the known safety and efficacy profile of Juxtapid.
Juxtapid is approved in the United States 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. In the US, Juxtapid carries a boxed warning for the risk of hepatotoxicity. The boxed warning also states that Juxtapid should only be prescribed to patients with a clinical or laboratory diagnosis consistent with HoFH, and that the safety and effectiveness of Juxtapid have not been established in patients with hypercholesterolemia who do not have HoFH. Because of the risk of hepatotoxicity and the importance of Juxtapid only being prescribed to patients with a clinical or laboratory diagnosis consistent with HoFH, Juxtapid is only available through the Juxtapid REMS Program. The effect of Juxtapid on cardiovascular morbidity and mortality has not been determined.
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.
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. The safety and effectiveness of Juxtapid have not been established in patients with hypercholesterolemia who do not have HoFH.