Today the cholesterol-fighting drug Lipitor is the best-selling pharmaceutical in history, with sales of about $125 billion since it was approved by the FDA in 1996. But in the early 1990s, the drug was an underdog, a barely viable “me-too” clone of other anti-cholesterol statin drugs, owned by the second-rate drug making division of a conglomerate that cared more about fish food than it did pharmaceuticals.
The clinical trials of the drug made the world take notice. Those trials were led by a young doctor named Donald Black, who fought for the drug every step of the way once he realized its potential. Black will speak at Rutgers Entrepreneurship Day Wednesday, October 16, on the New Brunswick campus. The event, “Collaborative Innovation: Progress Through Partnerships,” will run to 3:30 p.m. For information visit vpr.rutgers.edu.
A panel discussion with experts on funding technology, a presentation on the National Science Foundation’s transformative commercialization program, “speed networking” for entrepreneurs, and Black’s keynote are highlights.
Black grew up on an apple orchard in Brighton, Michigan. His mother was a secretary for the University of Michigan and his father repaired mechanical cash registers. Black, the first in his family to go to college, never considered a career as a medical doctor while he was growing up.
“I hadn’t known any physicians growing up,” he says. “It wasn’t like I was very well prepared to go into medicine or to run clinical trials.” But Black did well in school, and signed up for a six-year combined undergraduate/med school program, intending to become a psychiatrist.
Med school at the University of Michigan changed his mind about being a doctor. “I loved the intellectual side of it,” he says. “The thing I liked about medicine was the diagnosis. It was the intellectual challenge. I love mysteries. I read an article in the Journal of the American Medical Association about how doctors should always read Sherlock Holmes, and I’ve always felt the same way.”
Black trained in medicine and pediatrics and participated in a cardiology fellowship at the University of Cincinnati Medical Center, where he assisted in clinical trials of Lovastatin, the first statin to be approved. After attending business school, he went to work for Parke-Davis Warner-Lambert Company in Ann Arbor in 1990.
At the time, Parke-Davis, once the largest drug company in the country, had fallen on hard times. It had had a few bad products and was having trouble recruiting scientists. Black, in fact, was the only medical doctor on the Ann Arbor campus. The company had not launched a new drug in 15 years. “It was part of a diversified conglomerate that was more interested in Listerene, Entemmans baked goods, and Tetra fish food than it was in drugs,” Black recalls. Into this backwater came Black, who was interested in working on a compound that directly dissolved cholesterol in plaque. Instead, the company assigned its new recruit to study another statin drug.
Several statin drugs had already been approved for market by then, but Parke-Davis was hoping to capture a small share of the market by making a drug that was slightly different from the ones that had gone before, even if it wasn’t much better. “If you came in with the sixth or seventh beta blocker, you could still get 5 to 10 percent of the market if you found some little catch, like it was blue instead of red, or you could take it twice a day instead of three times, or you might find some sub-population that it was little bit better for,” Black says.
He says there was an internal debate within the company about whether to even pursue its own statin drug, when doctors were happy with the ones that were available. “Some were saying, this is probably small, but we could get our piece. Others were saying it’s silly to waste our money on something that’s just a me-too,” Black says.
Despite the ambivalence, Black ran a study with volunteers, the first time the new statin compound, synthesized in 1985, had been tested on humans. The results were extraordinary, with the test subjects showing a 60 percent reduction in cholesterol versus a 40 percent reduction among people who were taking other statin drugs.
Still, Black and Parke-Davis were not convinced they had a blockbuster on their hands. Doctors believed a 40 percent reduction was enough for patients to reach healthy cholesterol levels, and Black worried that the new compound was trading safety for efficacy — that is, because it was more effective, it was more dangerous, and not suited to prescribe over the long term. He decided to run another trial, one where the drug was given in very low doses. That trial was a success, and was the key to Lipitor’s conquest of the statin market. Effectiveness at lower doses meant prescribing it was simpler for doctors.
Lipitor practically sped through the FDA approval process because of another decision that Black made. The federal agency had a “fast-track” approval program available for drugs that were urgently needed to treat certain conditions. Black decided to see if the drug was effective against a deadly disease called hypercholesterolemia. This deadly disease comes in two varieties: homozygous and heterozygous. People with the heterozygous form of the disease can look perfectly healthy but drop dead of a heart attack in their 30s. The more deadly homozygous form affects about one in a million people. Those affected develop high cholesterol during childhood and can die of a heart attack in their early teens. It is hereditary and strikes people born into groups with small gene pools, like French Canadians, Afrikaans, or Ashkenazi Jews.
Black, with a team of just six people, decided to run a trial in South Africa to see if the new drug could save children’s lives. If it worked, the FDA would approve it very quickly. “We figured out a way to treat these kids and provide some benefit to them, but I was told that if anyone had any problems, I would be fired and they would kill the drug,” Black says. “They were worried about the risk of failure.”
Black says it often felt like he was fighting an uphill battle. The only thing working in Lipitor’s favor, Black says, was that the company didn’t really have any other options for new drug development. “Our backs were against the wall, and that was critical to our success,” he says. “I’ve seen it over and over again. Unless people feel like they are really up against it, you really can’t seem to get good innovation.”
The company only spent $60 million developing the drug. Today, an average drug costs $1 billion. The relatively small budget meant that Black could only test it on a limited number of subjects. In a normal clinical trial, there is one patient in the untested control group for every person in the experimental group, but in the Lipitor trials, only a fourth of the patients were controls.
Black also had a role in naming the drug. The name combines “Lipid” which is the type of molecule cholesterol is made of, and “tor,” which Black says was a favorite syllable of his growing up. Although Black didn’t know it at the time, “tor” also means “remove” in Japanese, so it worked out well.
When Parke-Davis realized it had a viable drug in Lipitor, it faced a business decision. Lipitor would be launched at the same time as a new kind of Listerene toothpaste. They didn’t have the cash to do both. So they made a deal with Pfizer. The drugmaker would give Werner-Lambert, which had acquired Parke-Davis, several billion dollars in exchange for half the Lipitor profits for the next few years.
After sales of the drug took off, Pfizer bought the company for $90.27 billion. Black went on to a career in R&D. For the next 10 years, he ran a laboratory in Ann Arbor for the man who had been his mentor at the University of Cincinnati Hospital. He moved to Princeton when he became head of global strategy for Merck. Later he was head of R&D for GE Healthcare Diagnostics. For the last four years, he has run his own company, Trialynx, which is based in Michigan and runs clinical trials. Black has three sons and lives in Princeton with his wife.
Today, by some estimates, about 30 million people take Lipitor. Black is one of them. “I thought, if anyone should get a side effect it should be me,” Black says. “I started taking it the minute it was available.”