* Regeneron drug cuts LDL up to 75 pct at 2-week dosing
* Researcher says potency waned with 4-week dosing
* Success of Amgen drug at 4-week dosing poses challenge
By Ransdell Pierson
CHICAGO, March 26 A new type of drug being
developed by Regeneron Pharmaceuticals Inc slashed
levels of cholesterol almost in half when given every four
weeks, but fell short of reductions reported a day earlier with
once-monthly injections of Amgen Inc's rival product.
Both monoclonal antibodies work by blocking a protein called
PCSK9, and are shaping up to be the next big thing in preventing
heart attack and stroke. Wall Street expects the new class of
drugs, including those in earlier stages of development at Merck
& Co and Bristol-Myers Squibb Co, to generate
annual future sales of up to $20 billion.
Regeneron is developing its entry, called REGN 727, in
partnership with French drugmaker Sanofi. The product,
which has completed mid-stage trials and is heading toward far
larger Phase III studies, has been considered to be the clear
Amgen's drug, AMG 145, is just entering mid-stage studies
and is considered about a year behind REGN 727 in development.
Although it is far less-known than the Regeneron antibody,
stellar results from a Phase I trial of the Amgen product raised
its profile considerably when reported on Sunday at the annual
sessions of the American College of Cardiology in Chicago.
In the 51-patient study, patients receiving monthly
injections of AMG 145 and taking low to moderate doses of
statins had up to a 66 percent reduction in "bad" LDL
cholesterol by the eighth week of the study.
"We gave two doses, four weeks apart, and at the eighth week
there was minimal tapering off" of the drug's potency, Clapton
Dias, Amgen's medical services director, told Reuters.
By contrast, data presented Monday at the Chicago heart
meeting showed that the effect of REGN 727 in a mid-stage trial,
when given at high doses every four weeks, tapered off
"The cholesterol lowering was consistent at two weeks, but
at four weeks you could see effectiveness of the drug begin to
wane," its lead researcher, James McKenney, said in an
"LDL began to come back up," said McKenney, who is chief
executive officer of Richmond, Virginia-based testing company
National Clinical Research. He speculated that future late-stage
trials of REGN 727 will therefore likely be built around
Given every two weeks, the Regeneron drug cut LDL levels up
to 72 percent, McKenney said. That is roughly in line with
maximum reductions of 75 percent seen with AMG 145. No serious
side effects have been reported for either medicine.
The conventional wisdom in the pharmaceutical industry is
that drugs given infrequently -- once a day instead of twice
daily, or monthly as opposed to biweekly -- have a decided
commercial advantage because of their greater convenience to
patients. It applies especially to injectable drugs.
Steven Nissen, head cardiologist at the Cleveland Clinic, on
Sunday said those assumptions are breaking down as more
injectable biotech medicines come to market.
He said he did not believe less-frequent dosing would render
a big advantage to either of the two companies.
A four-week dosing schedule may be "modestly more
attractive" to patients and doctors than injections every two
weeks, Nissen said in an interview at the heart conference.
"But the frequency is not a make-or-break consideration," he
added, because patients would be able to inject themselves with
the same types of tiny needles that are already widely used and
accepted for other conditions, including diabetes.
Although it did not pan out for monthly dosing, McKenney
said REGN 727 had "remarkable" and persistent potency when
patients received injections every two weeks along with one of
three available daily doses of Pfizer Inc's statin
Those receiving 50 milligram doses of Lipitor achieved an
additional 40 percent reduction in LDL cholesterol, beyond that
seen with patients taking Lipitor alone. He said 64 percent and
72 percent reductions in LDL were seen among patients who
received, respectively, 100 milligram or 150 milligram daily
doses of Lipitor.
"Forty percent, 64 percent, 72 percent reductions. I'm
saying, 'Wow!' -- I've never seen anything like this," McKenney
said, recalling his excitement when data from the
Regeneron-sponsored trial became unblinded. "In three decades of
doing clinical research in the cardiovascular field, this is the
most impressive drug I've ever seen, so I have great hope this
could be a breakthrough."
McKenney said REGN 727 and Lipitor, when taken together
virtually guarantee that patients will achieve their
"You've taken it to the limit. You can't lower LDL
cholesterol any more than bringing these drugs together."
But a growing number of drugmakers, including Amgen, can be
expected in coming years to challenge McKenney's thesis.