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Injected Kynamro Wins U.S. Approval; Faces Oral Foe Juxtapid in HoFH

By Randy Osborne
Staff Writer

Quelling fears that the FDA might follow Europe’s lead, regulators in the U.S. approved Kynamro (mipomersen), the apolipoprotein B synthesis inhibitor developed by Isis Pharmaceuticals Inc. for homozygous familial hypercholesterolemia (HoFH).

Carlsbad, Calif.-based Isis, partnered on Kynamro with Genzyme, a unit of Paris-based Sanofi SA, disclosed the news last night.

A first-in-class, second-generation antisense therapy, Kynamro in October met with a mixed but ultimately positive response when an FDA advisory panel managed to look past testimony about liver problems, cancer in mice, possible heart risk, immune-response glitches and trial dropout rates. Panelists voted 9-6 to recommend approval. (See BioWorld Today, Oct. 19, 2012.)

In December, the European Medicines Agency’s Committee for Medicinal Products for Human Use turned thumbs-down on Kynamro, saying the “intended cardiovascular benefit, in terms of reducing cholesterol levels, outweighed its cardiovascular risk.” The agency also cited flu-like symptoms, injection-site reactions and liver toxicity.

Though hardly moot, the U.S. approval of Kynamro squares the intravenous therapy off against recently approved Juxtapid (lomitapide) from Aegerion Pharmaceuticals Inc., of Bridgewater, N.J., which boasts oral dosing, a shorter half-life, and possibly better efficacy in lowering relevant lipids. J.P. Morgan analyst Cory Kasimov estimated Juxtapid will take 70 percent of the market. (See BioWorld Today, Dec. 27, 2012.)

Bigger money lies in heterozygous familial hypercholesterolemia (HeFH), much less uncommon than HoFH. But because more patients would be treated, Isis/Genzyme may have even more difficulty winning approval in this indication, given Kynamro’s known safety risks. Still, a trial called FOCUS is testing the drug in HeFH.

In mid-October, just ahead of the advisory panel meeting, the FDA published briefing documents pointing out that neoplasms developed in about 3 percent of patients treated with Kynamro, as compared to only 0.9 percent of those on placebo. The documents also noted the small clinical-trial sample size with short treatment time, and highlighted three deaths of Kynamro patients: two of heart attacks and another of acute liver failure. Isis’ shares (NASDAQ:ISIS) dropped almost 22 percent, closing at $10.27 that day. The stock closed Tuesday at $13.38, down 11 cents prior to release of the news. This morning it was up 13.23 percent in premarket trading.

Isis faces class-action lawsuits such as the one by Howard Smith, an attorney in Bensalem, Pa., who took the action on behalf of buyers of Isis stock between March 29, 2012, and October 15, 2012. During that period, Smith claims, Isis “issued materially false and misleading statements regarding the safety and efficacy” of Kynamro.