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elevations in liver enzymes that were triple normal levels, which can be an indicator of liver damage. Six of the 34 mipomersen patients (18 percent) dropped out of the study, including two for swelling around their injection sites, one for the elevated liver enzymes, one for rash, one for personal reasons, and another for non-compliance with study protocol.
Raal, in his comments to investors during today’s webcast, noted that it’s common to see increases in liver enzymes in patients taking cholesterol-lowering drugs. No patients had their liver enzymes run so high that they were classified at high risk under something called Hy’s Law. That’s a severe condition in which drugs damage the liver, which leads to jaundice and without a liver transplant can be fatal in 10 to 50 percent of cases, according to this Wikipedia entry.
“All lipid-lowering drugs are associated with” elevated liver enzymes, Raal said during a question-and-answer session with analysts. “We in this field see it almost as the liver turning up its thermostat.” He said that he’s never seen liver enzymes rise high enough to turn into a severe case like those classified by Hy’s Law. “This isn’t a scary thing,” Raal said.
Still, it’s obviously a black mark for a drug to have doctors even thinking about that much potential liver damage, so it’s no surprise that Isis and Genzyme are backing off on the dose of mipomersen in some future trials. Two new studies are being planned to look at different doses and schedules, including one that will compare a 30 milligram daily shot, a 70 milligram three-times-weekly injection, and the 200 milligram weekly dose that was used in this first pivotal trial.
Genzyme also says it is still refining its game plan for how to get approval of mipomersen in the U.S. and Europe. The company plans to file its application with regulators in the U.S. and Europe in mid-2011. That represents a bit of a delay, according to Leerink Swann analyst Joseph Schwartz, who was quoted by Reuters. Genzyme had previously said it would turn in the regulatory filing in the second half of 2010, according to the Reuters report.