Her cholesterol was astoundingly low. Her low-density
lipoprotein, or LDL, the form that promotes heart disease, was 14, a level
unheard-of in healthy adults, whose normal level is over 100.
The reason was a rare gene
mutation she had inherited from both her mother and her father. Only one other
person, a young, healthy Zimbabwean woman whose LDL cholesterol was 15, has
ever been found with the same double dose of the mutation.
The discovery of the mutation
and of the two women with their dazzlingly low LDL levels has set off one of
the greatest medical chases ever. It is a fevered race among three
pharmaceutical companies, Amgen, Pfizer and Sanofi, to test and win approval
for a drug that mimics the effects of the mutation, drives LDL levels to new
lows and prevents heart attacks. All three companies have drugs in clinical
trials and report that their results, so far, are exciting.
“This is our top priority,” said
Dr. Andrew Plump, the head of translational medicine at Sanofi. “Nothing else
we are doing has the same public health impact.”
Dr. Gary H. Gibbons, the
director of the National Heart, Lung, and Blood Institute, estimates that even
if the drugs were expensive and injected as many as two million Americans might
be candidates. But if they could eventually be made affordable and in pill form
— two very big ifs — they might be used by one in four adults, he said.
Despite major gains over the
past half-century, heart disease remains the leading killer of Americans,
causing nearly 600,000 deaths a year. Statins, the cholesterol-lowering drugs
that went on the market in 1987, were a huge breakthrough, but far from a
panacea.
The companies and many heart
researchers hope they are closing in on a blockbuster, buoyed by success with
preliminary studies. But Dr. Gibbons cautioned that critical large-scale
studies that would tell whether the drugs actually prevent heart attacks and
deaths are only starting.
“That will show if they are a
game changer,” he said.
So far, people with stubbornly
high cholesterol levels who are taking the drugs in preliminary studies have
seen their LDL levels plunging from levels well over 100 to 50, 40, or even
lower. Like insulin for diabetes, the drugs are injected, but they are taken
once or twice a month.
Dr. Barry Gumbiner, who is
directing Pfizer’s studies, said the company had to decide whether to set a
floor for patients’ LDL levels. Pfizer is interrupting treatment when LDL
levels reach 25 or lower. The people seemed fine, but the company got nervous.
“There is not a lot of
experience treating people to LDL levels this low,” Dr. Gumbiner said.
And there is another concern:
cost. Each company’s drug is a biologic, a so-called monoclonal antibody made
in living cells at an enormous expense, like some new cancer drugs that are
already straining the medical system. Amgen plans to make metric tons of its
drug, much more, the company says, than any other biologic.
