Amgen drug lowers cholesterol up to 66 pct in pivotal studies

WASHINGTON, March 29 Sat Mar 29, 2014 2:00pm EDT

WASHINGTON, March 29 (Reuters) - Amgen Inc's drug from a high profile new class of experimental medicines lowered "bad" LDL cholesterol by 55 percent to 66 percent compared with a placebo in a trio of late-stage clinical trials, according to data presented on Saturday.

Amgen had previously said the drug, evolocumab, met the main goals of five late-stage trials involving some 4,000 patients by significantly outperforming placebo or another cholesterol medicine in a variety of patient populations.

Saturday's presentation at the American College of Cardiology scientific meeting in Washington marked the first time the magnitude of LDL lowering and other details from the late stage studies were unveiled. Results of the other two Phase III studies will be presented at the meeting on Sunday.

The data also showed that two dosing regimens of the injected drug - 140 milligrams every two weeks or 420 mg once a month - were equally effective in reducing LDL levels.

"We're seeing excellent efficacy and the safety profile appears no different than placebo, so you can't get better than that," Dr. Michael Koren, one of the lead investigators on two of the evolocumab studies, said in a telephone interview.

Evolocumab belongs to a highly promising class of drugs called PCSK9 inhibitors that block a protein that reduces the liver's ability to remove LDL from the blood. They are expected to be used in patients who cannot tolerate widely used and highly effective statins, such as Pfizer Inc's Lipitor, and in those unable to get their cholesterol levels low enough using currently available medicines.

"In terms of the LDL lowering, these drugs are as good or better than anything we have," said Koren, who presented data from the trial called Mendel-2 at the ACC meeting.

In that 614-patient study, evolocumab reduced LDL 55-57 percent more than a placebo and up to 40 percent more than Merck & Co's cholesterol fighter Zetia in patients not on any other cholesterol drugs.

It also helped about 70 percent of patients get their LDL down to 70 or lower, Koren said. That had been the target for high risk patients before controversial new guidelines announced last year eliminated specific target numbers.

Amgen said it will file its application seeking U.S. approval of evolocumab sometime this year. The drug is expected to compete with similar medicines also in late stages of development from Regeneron Pharmaceuticals Inc in partnership with Sanofi and from Pfizer.

Analysts have forecast eventual annual sales of $3 billion or more for each of the drugs, assuming insurers agree to pay for them. Some industry analysts expect them to cost thousands of dollars a year, far above the costs of statins.

The companies are conducting large, so-called outcomes studies to prove that the new medicines reduce heart attacks and strokes, as statins have, in addition to dramatically lowering LDL levels. The FDA has indicated that it would not necessarily wait for results from those years-long trials to approve the drugs.

Earlier this month, the FDA asked companies developing PCSK9 inhibitors to assess potential cognitive impairment side effects that have been reported with some cholesterol drugs.

"I can tell you in Medel-2 there was no (cognitive impairment) signal whatsoever," said Koren, chief executive of the Jacksonville Center for Clinical Research in Florida.

Scott Wasserman, Amgen's executive medical director for global development, said the same has been true of other evolocumab studies.

"We've looked at our data very, very carefully and are continuing to look at it very carefully in combination with the FDA. We haven't seen any (neurocognitive) safety signals," Wasserman said in a telephone interview.

In the study called Descartes, a 52-week trial of 901 patients already on statins or other lipid lowering medicines, evolocumab on average lowered LDL by 57 percent versus placebo.

The 329-patient, 12-week Rutherford-2 study tested the Amgen drug in subjects with familial hypercholesterolemia, a genetic condition involving extreme, dangerously high cholesterol. For those patients, who were already on statins and other lipid lowering therapies, evolocumab took down LDL levels by 59-66 percent compared with placebo.

Koren said he expects the first PCSK9 approvals to come for that patient population with additional approvals to follow for those who can't take statins.

"It's really the most exciting story since statins, no question, and I think that's pretty universally held in the preventive cardiology community," Koren said. (Editing by David Gregorio)

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