No, Again: European Regulators Refuse Mipomersen

Shelley Wood

March 22, 2013

LONDON — Amid a slew of other recommendations issued today, the European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) has once again recommended that mipomersen (Kynamro, Genzyme Europe) not be approved in the EU[1].

The manufacturer had been seeking its approval for the treatment of patients with certain forms of familial hypercholesterolemia. As reported by heartwire , the EMA already declined to approve the drug in December, citing safety concerns.

In the interim, the US FDA, following the advice of an advisory panel last October, announced in January that it had approved the drug, a once-weekly subcutaneous injection, as an adjunct to maximally tolerated lipid-lowering medications and diet for the treatment of patients with homozygous familial hypercholesterolemia.

In reiterating its position today, the CHMP's "negative opinion" states that its main concerns include:

  • A high rate of drug discontinuation within two years, due to side effects.

  • Long-term consequences of fatty buildup in the liver, increased enzyme levels, and possible irreversible liver damage.

  • A higher rate of cardiovascular events among patients taking the drug.

These concerns, the note reads, "prevented the CHMP from concluding that Kynamro's intended cardiovascular benefit, in terms of reducing cholesterol levels, outweighed its potential cardiovascular risk. . . . During the reexamination in March 2013, the CHMP's concerns remained unresolved and were not fully addressed by measures proposed by the company."

In the US, the FDA is requiring a risk evaluation and mitigation strategy (REMS) for mipomersen in the US, to ensure safe use, and four postmarketing studies.

In separate announcements today, the EMA recommended extending the indication for rivaroxaban (Xarelto, Bayer Pharma/Janssen Pharmaceuticals) to include prevention of atherothrombotic events in adult patients with acute coronary syndromes, and also recommended restricting use of the antiplatelet drug cilostazol to limited subgroup of patients with PAD.