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 Gibbons cautioned that critical large-scale studies that would tell whether the drugs prevent heart attacks and deaths are only starting.
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.
Insurers generally pay for drugs approved by the Food and Drug Administration, and the number who might benefit from these cholesterol drugs dwarfs those who are helped by the biologic cancer drugs.
If the drugs come into use, researchers are asking, can cholesterol go too low?
The data point to increasing benefits with lower and lower LDL levels, said Dr. Daniel J. Rader, a cholesterol researcher at the University of Pennsylvania and a consultant for Sanofi on its drug.
“If I had coronary disease, I would definitely try to drive my LDL to well below 50,” Dr. Rader said.
But with LDL levels falling so low in studies, Dr. Gibbons said, “We are in uncharted territory.” The drug companies have been transfixed by the idea, and each wanted to be the first to market it.
The prospect “was so hot it sizzled,” said Dr. Steven Nissen, the chairman of the department of cardiovascular medicine at the Cleveland Clinic and leader of an Amgen trial.
Amgen has readied three factories, in Colorado, Puerto Rico and Rhode Island, to make its drug. It is anticipating production on a scale never attempted before with a monoclonal antibody, a costly wager for a drug still being tested and likely years from approval.
A $70 million, four-story factory in West Warwick, R.I., is like something out of Brobdingnag in “Gulliver’s Travels,” a land populated by giants. At every stage of production, familiar science equipment has been blown up to a huge scale. Antibody-producing cells that would be housed in a glass flask in a research laboratory are grown in a stainless steel tank nearly the size of a fuel tank on a semi truck.
The companies want to be ready with large quantities of their versions of the drug if they are approved.
“The race is on to see who can do it,” said Dr. Joseph P. Miletich, the head of research and development translational sciences at Amgen. As their factories were starting to produce the drugs, the companies began recruiting patients who were worried enough about their LDL levels to inject themselves with an experimental substance.