Aegerion Pharmaceuticals, Inc. today announced that the US Food & Drug Administration (FDA) has approved JUXTAPID™ (lomitapide) capsules as an adjunct to a low-fat diet and other lipid-lowering treatments, including LDL 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) in patients with homozygous familial hypercholesterolemia (HoFH).
"We are excited that JUXTAPID will become a new treatment option for patients with HoFH," said Marc Beer, Chief Executive Officer at Aegerion.
"The approval of our first product also marks an important corporate milestone for Aegerion and reflects our commitment to help patients in need."
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 elevation of blood cholesterol levels. HoFH patients often develop premature and progressive atherosclerosis, a narrowing or blocking of the arteries.
"The FDA approval of JUXTAPID is a major step forward for HoFH patients and their families, who have long been waiting for new therapies," said Katherine Wilemon, president and founder of The FH Foundation. "New treatments, combined with further understanding and awareness of this disease, can bring much needed hope to the HoFH community."
JUXTAPID contains a Boxed Warning citing the risk of hepatic toxicity. See below for Important Safety Information about JUXTAPID, including the Boxed Warning, Contraindications and Warnings and Precautions. The safety and effectiveness of JUXTAPID have not been established in patients with hypercholesterolemia who do not have HoFH.
The effect of JUXTAPID on cardiovascular morbidity and mortality has not been determined. The safety and effectiveness of JUXTAPID have not been established in pediatric patients.
The FDA based its approval of JUXTAPID on Aegerion's pivotal Phase III study, which evaluated the safety and effectiveness of the medicine to reduce LDL-C levels in 29 adult patients with HoFH.
The study was a multinational, single-arm, open-label, 78 week trial that was recently published in the November 2, 2012 online version of The Lancet. In this study, JUXTAPID was initiated at 5 mg daily and gradually escalated to doses of 10 mg, 20 mg, 40 mg, up to 60 mg, based on tolerability and acceptable liver enzymes levels.
When added to the existing lipid-lowering therapy of the HoFH patients in the study, JUXTAPID 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 with last observation carried forward for the patients who discontinued prematurely. LDL-C was reduced by an average of 50 percent for 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 were allowed. Average reductions in LDL-C were sustained during chronic therapy.
The most common adverse reactions in the Phase III trial were gastrointestinal, reported by 27 (93%) of 29 patients. Adverse reactions, which were reported by ≥8 patients (28%) in the HoFH clinical trial, included diarrhea, nausea, vomiting, dyspepsia and abdominal pain. Other common adverse reactions, reported by 5 to 7 (17-24%) patients, included weight loss, abdominal discomfort, abdominal distension, constipation, flatulence, increased ALT, chest pain, influenza, nasopharyngitis and fatigue.
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 1 percent to a median absolute increase of 6 percent at 26 and 78 weeks.
Because of the risk of liver toxicity, JUXTAPID is available only through a restricted program called the JUXTAPID Risk Evaluation and Mitigation Strategy (REMS) Program. Aegerion will certify all healthcare providers who prescribe JUXTAPID and the pharmacies that will dispense the medicine.
The goals of the REMS are to:
- Educate prescribers about the risk of hepatotoxicity associated with the use of JUXTAPID;
- Educate prescribers about the need to monitor patients during treatment with JUXTAPID as per product labeling;
- To restrict access to therapy with JUXTAPID to patients with a clinical or laboratory diagnosis consistent with HoFH;
- To clarify that the safety and effectiveness of JUXTAPID have not been established in patients with hypercholesterolemia who do not have HoFH; the effect of JUXTAPID on cardiovascular morbidity and mortality has not been determined; and the safety and effectiveness of JUXTAPID have not been established in pediatric patients.
- To further understand JUXTAPID's long-term safety and effectiveness, Aegerion has made a commitment to the FDA to conduct a post-approval, observational cohort study.
As part of the planned launch of JUXTAPID, the company has developed a comprehensive support services program for patients and their healthcare providers. For more information, call this toll-free number, 1-85JUXTAPID (1-855-898-2743).