| LOS ANGELES
LOS ANGELES Nov 5 A new class of experimental
cholesterol-lowering drugs demonstrated a promising new
technique for reducing levels of the artery-clogging fatty
deposits in mid-stage studies.
The medicines, which are man-made antibodies, lowered "bad"
cholesterol by more than 40 percent and up to 80 percent in
small Phase 2 studies released by Amgen Inc and Pfizer
Inc on Monday at the annual scientific meeting of the
American Heart Association in Los Angeles.
The drugs, given by injection every two or four weeks, are
part of a group of biotech medicines known as PCSK9 inhibitors
designed to target a protein that prevents the body from
removing artery-blocking LDL cholesterol from the bloodstream.
The most commonly used cholesterol-lowering drugs - statins
such as Pfizer's Lipitor and AstraZeneca's Crestor -
work by preventing the liver from making cholesterol.
The expiration of patents on all but one of that top-selling
class of heart medicines - Crestor - has eroded one of the main
sources of drug company profits.
Mean annual sales of 15 different categories of heart drugs
are set to fall by more than a quarter by 2017, from $83 billion
in 2011 to $60 billion, according to consensus analyst forecasts
compiled by Thomson Reuters Pharma.
Analysts have said the PCSK9 drugs could generate billions
of dollars in annual sales.
The experimental drugs from Pfizer and Amgen proved
effective in lowering LDL cholesterol by significant amounts in
patients genetically predisposed to high cholesterol and in
patients unable to tolerate statins, according to the mid-stage
The drugmakers aim, however, is to also show the new drugs
can lower the risk of heart disease in a much broader group of
patients who are not able to control their cholesterol with
statins and other drugs, such as Merck and Co's Zetia.
Partners Regeneron Pharmaceuticals <REGN.O) and Sanofi
announced on Monday the launch of an 18,000-patient
trial of their once-every-two-weeks PCSK9 inhibitor to see if it
cuts the risk of heart attacks, strokes and death, putting them
ahead of the field pursuing the new class of drugs.
Roche is also developing a PCSK9 drug.
RBC Capital Markets analyst Adnan Butt estimated that there
are roughly 1 million U.S. patients who are intolerant to
statins and another 11 million whose cholesterol is poorly
controlled by the drugs.
In a Phase 2 trial, Amgen's drug AMG145 showed it can reduce
LDL levels by as much as 55 percent when combined with statins
in patients genetically predisposed to high cholesterol. After
12 weeks, patients treated with a low dose of AMG145 had a 43
percent reduction in LDL, while those given a higher dose had a
drop of 55 percent. Patients treated with a placebo saw a 1
percent increase in LDL cholesterol.
A second Phase 2 trial of AMG145 found that it reduced LDL
by up to 51 percent in patients unable to tolerate statins. When
those patients were treated with AMG145 and ezetimibe - the
chemical name for Zetia, LDL fell by 63 percent.
The trial results were generally in line with expectations,
said RBC Capital Markets analyst Michael Yee.
Amgen will present more AMG145 trial results on Tuesday,
including a mid-stage trial in patients with uncontrolled
cholesterol despite statins, which Yee said will be more
Sean Harper, head of research and development at Amgen, told
Reuters in a telephone interview that the company plans to
launch pivotal-stage trials of the drug early next year.
He said the company will conduct a broader Phase 3 trial
designed to see whether AMG145 can lower the risk of heart
problems, and it was "not unreasonable" to assume that such a
trial would take five years to yield results.
Pfizer, which slightly lags Amgen and Regeneron in
development of its experimental PCSK9 inhibitor, presented
mid-stage trial data showing that its drug, RN316, also
significantly lowers LDL cholesterol levels.
In a 12-week trial of about 130 patients already on high
doses statins, the Pfizer drug cut LDL cholesterol by 56 percent
at the highest dose of 6 milligrams/kilogram of weight. The 3
mg/kg dose lowered LDL levels by 46 percent on top of statins,
according to data unveiled on Monday.
Barry Gumbiner, executive director of clinical research for
Pfizer's PCSK9 program, said the results were somewhat
misleading because any patient whose LDL level fell below 25 had
doses withheld as a precaution, skewing the overall results.
After four weeks, patients on the highest dose had LDL
reductions of up to 80 percent before some had doses withheld,
The Pfizer drug was administered intravenously once every
four weeks for a total of three dosings in the brief
proof-of-concept trial. Subsequent trials will use a version
injected under the skin, with the next Phase II study designed
to determine which doses of the drug will be advanced into much
larger, late-stage studies, the company said.
Pfizer researchers said the drug appeared to be
well-tolerated, with no allergic reactions or safety issues of
concern cropping up in the small study.
(Reporting By Deena Beasley and Bill Berkrot in Los Angeles;
Editing by Leslie Adler)