WASHINGTON A U.S. Food and Drug Administration panel of outside experts recommended the Sanofi SA and Isis Pharmaceutical Inc drug, Kynamro, for treatment of a rare genetic disorder that causes unusually high cholesterol and life-threatening cardiovascular disease.
In a 9-6 vote on Thursday, the FDA advisory committee concluded that company-provided research showed the 200 milligram injection to be safe and effective enough for the one in 1 million Americans who have homozygous familial hypercholesterolemia, or HoFH, and are already on a cholesterol treatment regimen that includes lipid-lowering medication.
The panel's recommendation, reached despite misgivings about side-effects, including liver problems and a potentially higher risk for cancer, will now be considered by FDA regulators as they decide by the end of January whether to grant final approval for the drug known generically as mipomersen sodium.
The shares of Isis, which developed the drug in cooperation with Sanofi, were halted on Thursday because of the FDA meeting. They closed at $9.62 on Wednesday. Sanofi's shares closed up 1.3 percent at 69.65 euros in Europe before the panel reached its decision.
The recommendation came in the same week as FDA advisers recommended approval for Aegerion Pharmaceuticals Inc's HoFH drug, lomitapide, with a decision by the regulatory agency expected before the end of December.
The FDA would impose risk mitigation strategies to control the use of both drugs because of safety concerns, including a buildup of fatty tissues in the liver, a condition that can lead to serious liver damage and cardiovascular disease over time.
FDA officials said they would seek to ensure maximum benefits for HoFH patients, whose clogged arteries pose a lingering danger of heart attack and early death.
Sanofi's Genzyme unit said it would also create a registry to monitor patients and collect data on the drug's effects.
DROP IN "BAD CHOLESTEROL"
HoFH patients who received Kynamro saw their low-density lipoprotein cholesterol, or "bad" cholesterol, levels drop nearly 22 percent further than those who received a placebo. But some panel members called that a "moderate" improvement and said it was unclear how effective the drug might be at reducing bad cholesterol to medically acceptable levels or helping HoFH patients avoid cardiovascular disease.
"There's not a whole lot of treatment options for patients with this (disease)," the panel's patient advocate, Ida Spruill of the Medical University of South Carolina, said in explaining her vote to recommend Kynamro.
But Dr. Robert Smith of Brown University, who voted against recommendation, said the drug's ability to help some patients was not enough to outweigh potential health risks.
"I felt it was critical not to let that become an enthusiasm that might cloud my willingness to consider the adverse effects that might be associated with this medication," he said.
Research showed risks for hepatitis, as well as abnormal growths that occurred in about 3 percent of patients who took the drug. The growths were malignant in six cases. Company officials said malignancies did not occur among HoFH patients, but rather among older participants with other cholesterol problems. Panel members said tests in animals also suggested a possible cancer link.
Adverse events, which also included flu-like symptoms and skin reactions, caused a large number of patients to drop out of studies and panel members recommended regular testing among those who take the drug to monitor liver health.
But actual health risks are unclear because of the limited size and duration of the research, which did not include a large safety trial.
The committee heard testimony from several HoFH sufferers who described Kynamro's effectiveness at reducing their bad cholesterol levels.
But some experts expressed concern the FDA's plan to ensure the drug's safe use in the marketplace might not go far enough to restrict the drug's use to those who need it most.
Critics say the share prices of companies involved in Kynamro and lomitapide have moved sharply on Wall Street due to speculation that physicians would prescribe both drugs off label to a wider population of patients with cholesterol problems.
Washington-based advocacy group Public Citizen says the new drugs, with price tags estimated as high as $300,000 a year, are likely to be too expensive for many of the 300 people in the United States with HoFH, who can receive blood-cleansing apheresis treatments for less than one-third the cost.