Genzyme, a Sanofi company (EURONEXT: SAN and NYSE: SNY), and Isis Pharmaceuticals Inc. (NASDAQ: ISIS), today announced that the U.S. Food and Drug Administration (FDA) has approved its New Drug Application (NDA) for KYNAMROTM (mipomersen sodium) injection. KYNAMRO, given as a 200 mg weekly subcutaneous injection, has been approved as an adjunct to lipid-lowering medications and diet to reduce low density lipoprotein-cholesterol (LDL-C), apolipoprotein B (Apo B), total cholesterol (TC), and non-high density lipoprotein-cholesterol (non HDL-C) in patients with homozygous familial hypercholesterolemia (HoFH).
"Today's FDA approval of KYNAMRO is great news for patients with HoFH who are in need of additional treatment options for this rare, and often under-diagnosed disease," said Genzyme President and CEO, David Meeker, M.D. "As the leader in treatments for rare diseases, we are pleased to bring our expertise to HoFH patients living with this serious condition to better help them manage their disease."
HoFH is a rare inherited condition that makes the body unable to remove LDL cholesterol, often called the "bad" cholesterol, from the blood, causing abnormally high levels of circulating LDL cholesterol. In the United States, HoFH, an orphan indication, occurs in approximately one in one million individuals. For those with HoFH, heart attacks and death often occur before age 30.
"People living with Homozygous FH may not appear to be sick, but they live with the burden of this rare disease every day," said Katherine Wilemon, President and Founder the FH Foundation "The approval of KYNAMRO gives the HoFH community hope that HoFH can be effectively managed."
The FDA approval triggers a $25 million milestone payment to Isis from Genzyme.
"KYNAMRO is the first systemic antisense drug to reach the market and is the culmination of two decades of work to create a new, more efficient drug technology platform. As evidenced by our robust pipeline, our antisense drug discovery technology is applicable to many different diseases, including the treatment of a chronic and rare disease, like HoFH," said Stanley T. Crooke, M.D., Ph.D., Chairman of the Board and CEO of Isis. "We look forward to continuing to work with Genzyme toward a successful commercial launch of KYNAMRO and global expansion into other markets."
The FDA approval for KYNAMRO is supported by the largest clinical trial conducted to-date in the HoFH patient population. The randomized, double-blind, placebo-controlled, multi-center trial enrolled 51 patients age 12 to 53 years, including 7 patients age 12 to 16 years, who were maintaining a regimen of maximally-tolerated lipid lowering medications. Treatment with KYNAMRO further reduced LDL-C levels by an average of 113 mg/dL, or 25%, from a treated baseline of 439 mg/dL, and further reduced all measured endpoints for atherogenic particles. In March 2010, these data were published in The Lancet by Professor Raal, University of the Witwatersrand in South Africa.
Safety data for KYNAMRO are based on pooled results from four Phase 3, randomized, double-blind, placebo-controlled trials with a total of 390 patients of which 261 patients received weekly subcutaneous injections of 200 mg of KYNAMRO and 129 patients received placebo for a median treatment duration of 25 weeks. Eighteen percent of patients on KYNAMRO and 2% of patients on placebo discontinued treatment due to adverse reactions. The most common adverse reactions in patients treated with KYNAMRO that led to treatment discontinuation and occurred at a rate greater than placebo were: injection site reactions (5.0%), alanine aminotransferase (ALT) increased (3.4%), flu-like symptoms (2.7%), aspartate aminotransferase (AST) increased (2.3%), and liver function test abnormal (1.5%).
KYNAMRO is an antisense drug and is metabolized without affecting the CYP450 pathways used in commonly prescribed drugs, and thus has potential for no drug-drug interactions. No clinically relevant pharmacokinetic interactions were reported between KYNAMRO and warfarin, or between KYNAMRO and simvastatin or ezetimibe.
KYNAMRO contains a Boxed Warning citing the risk of hepatic toxicity. Patients taking KYNAMRO should have liver enzyme testing before starting the drug and periodically thereafter. See below for Important Safety Information about KYNAMRO.
The safety and effectiveness of KYNAMRO have not been established in patients with hypercholesterolemia who do not have HoFH. The effect of KYNAMRO on cardiovascular morbidity and mortality has not been determined.
Because of the risk of hepatotoxicity, KYNAMRO is available only through a Risk Evaluation and Mitigation Strategy (REMS) called the KYNAMRO REMS. The goals of the KYNAMRO REMS are:
To educate prescribers about the risk of hepatotoxicity associated with the use of KYNAMRO, and the need to monitor patients during treatment with KYNAMRO as per product labeling.
To restrict access to therapy with KYNAMRO to patients with a clinical or laboratory diagnosis consistent with homozygous familial hypercholesterolemia (HoFH).
As part of its commitment to HoFH patients, Genzyme has developed KYNAMRO CornerstoneSM, an HoFH and KYNAMRO support program for healthcare providers, patients, and their families. KYNAMRO Cornerstone services include:
Dedicated KYNAMRO Cornerstone Case Managers.
Product & disease education for providers, patients, and families.
In-person injection training, if requested.
Reimbursement support, including out-of-pocket financial support, for patients who qualify.
Coordination of KYNAMRO shipment and delivery.