CardioExchange Archive

The FDA said today that it had granted approval to the novel cholesterol-lowering drug mipomersen sodium for use as an adjunct to diet and drug therapy in patients with homozygous hypercholesterolemia. The drug, which was developed by Isis Pharmaceuticals, will be marketed under the brand name of Kynamro by Genzyme.

Kynamro was approved as an orphan drug, which the FDA describes as meaning it was developed to treat a condition affecting less than 200,000 people. The standard of approval for orphan drugs is less rigorous than other drugs. There has been some confusion about the number of people who have homozygous familial hypercholesterolemia.  The FDA and ISIS/Genzyme said the condition affects about one in every million people.

In December the FDA approved lomitapide (Juxtapid, Aegerion) for the same condition. These are the first drugs specifically developed and approved for familial hypercholesterolemia.

Kynamro will carry a boxed warning about the serious risk of liver toxicity. Clinical studies with the drug found that it raised liver enzymes and led to accumulation of fat in the liver. The FDA said this “could lead to progressive liver disease with chronic use.”

Kynamro was approved with a Risk Evaluation and Mitigation Strategy (REMS) which will require certification of prescribers and pharmacies, as well as documentation that the drug is being properly used with each new prescription.

The FDA said the most common adverse reactions with Kynamro were injection site reactions, flu-like symptoms, nausea, headache, and elevations in liver enzymes.

The FDA is requiring the sponsor to perform four postmarketing studies, including a long-term registry of patients to assess the long-term safety of the drug, and an enhanced pharmacovigilance program to monitor potential problems.

“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 Crooke, the chair and CEO of Isis, in a press release.

In October, an FDA advisory panel voted to recommend approval of mipomersen, though the panel expressed considerable caution about the potential for liver damage. In December the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency recommended that the drug not be approved for use in Europe.