Healthy Skepticism Library item: 1491

Warning: This library includes all items relevant to health product marketing that we are aware of regardless of quality. Often we do not agree with all or part of the contents.

Publication type: news

Hall S.
Quest for hot new drugs spikes costs: High failure rate, time they take to develop hurt companies
The Detroit News 2003 Nov 23

Full text:

Pfizer scientists in Ann Arbor work under a quota to develop one successful drug a year until 2005.

Most Pfizer scientists are utter failures.

Like other drug researchers, they can spend their careers searching for new medicines only to retire without ever working on a drug that makes it to a pharmacy shelf. For every successful drug, there are 5,000 unsafe or ineffective failures.

Those odds increase research costs, to $802 million per drug in 2002, and contribute to high price tags for consumers — all driving a national debate on prescription drug costs that is prompting lawmakers to debate an unprecedented $400 billion reform to Medicare.

The key to survival for all drugmakers: producing blockbuster drugs like Pfizer Inc.‘s cholesterol-lowering Lipitor, invented by Ann Arbor scientists in 1990.

Last year, Lipitor became the largest-selling pharmaceutical ever with $8 billion in sales. It’s the giant success that pays for the thousands of small failures.

For researchers at Pfizer’s Ann Arbor labs, which employ 2,500 people, the quest for the blockbuster drug has been especially frustrating.

After a nearly decade-long dry spell, researchers at the lab think they’ve come across their next big hit — an anti-seizure, pain and psychiatric drug called Pregabalin that’s under review by the U.S. Food and Drug Administration, the last hurdle before the drug can go to market.

Analysts say the new Pregabalin has wide-reaching potential and could help Pfizer pay the crushing price of research.

But the scientists in Ann Arbor can’t afford to rest.

They are working under a new quota: one successful drug a year until 2005, and then two a year until 2008.

That’s a tough measure considering the Ann Arbor labs have only developed seven marketable drugs since 1938.

Everyone involved knows the stakes, especially David Canter, the affable head of research and development for Pfizer’s sites in Ann Arbor and Kalamazoo. Missing the quotas could mean “leadership changes.”

“We as a company can’t afford a series of lean years,” he said.

To be sure, Pfizer has improved its odds by merging with other drugmakers — including Kalamazoo-based Pharmacia earlier this year — pouring millions into advertising and employing an army of sales representatives to stoke interest in their drugs among doctors.

And in some cases, Pfizer has chosen the me-too approach — developing drugs similar to successful pills already on the market rather than focusing on breakthrough drugs. Lipitor hit shelves a full decade after the first cholesterol-fighting statins became available.

The results: $9 billion in company profits in 2002. Still, Pfizer’s future success is far from a lock.

As drugs like Lipitor lose their patents — opening the door to generics that drive down prices — Pfizer needs new revenue sources. “You have to keep reinventing your product pipeline in this industry or you go under,” Canter said.

Just last week, the Ann Arbor labs moved a step closer to success with a new type of insomnia drug, which was approved for widespread clinical trials. As for next year, there are five potential drugs that could begin testing in humans. But all it would take is a poor test result or unforeseen side effect to derail the drugs.

Inventing new drugs is no easy task. Industrywide, the introduction of new drugs plunged last year to 17 from a high of 53 in 1996, despite a near doubling in annual research spending to $32 billion.

“The diseases we’re trying to treat and cure today are all very complicated,” said Jeff Trewhitt, spokesman for the Pharmaceutical Research and Manufacturers of America trade group. “The learning curve is very steep.”

And the bottom could fall out any time on a promising new product. Last month, Pfizer scraped an anxiety medication it spent two years and $40 million developing because it caused brain changes in rats.

“We’re trying to shoot for a world where we’re successful 10 percent of the time,” said John LaMattina, Pfizer’s president of global research and development. “That may seem pretty pathetic, but you have to realize it’s a very difficult and costly business.”

Pfizer and other drug companies get little sympathy from customers struggling to pay for prescription drugs. To Eleanor Metcoff, a retired office manager from West Bloomfield, drug prices still seem exorbitant.

She was paying $150 a month for Lipitor, but recently switched to a generic medicine.

“I know research and development is expensive, but this is such a great drain on me,” she said.

For consumers, the complexities of prescription drugs are often missed, Pfizer’s Canter said.

“People have no problem spending thousands of dollars on an Intel computer chip because they can see it has hundreds of little plastic legs and electronic receptors,” he said. “Well, one of our tablets has one trillion of the highest quality molecules that will inhibit a process in your body. The problem is it looks like a little white tablet.”

Inventing that white tablet begins with chemists and biologists targeting a disease they want to cure or prevent. They search for a chemical reaction in the body that causes the disease, then hunt for a way to stop it.

At this point, any potential drugs are at least 12 years away from a pharmacy.

“I compare it to Martians trying to put out a fire on Earth,” said John Keenan, public affairs manager for Pfizer’s Ann Arbor labs. “From their spaceship, they’d see flames, red trucks, people trying to escape the fire and flashing lights.

“What if they decided to get rid of the red trucks and see if that stops the fire?”

The hunt for a molecule to halt disease begins in Pfizer’s Ultrahigh Throughput Screening lab, where chemists use machines the size of minivans to create thousands of tiny chemical reactions at once.

Chemists study a million molecules and identify several thousand that impact a disease.

More scientists manipulate those molecules virtually with 3-D computer screens, to find one that best targets the disease.

Then the testing begins. Scientists must determine if the molecule, or potential drug, is safe, effective against disease, reproducible and stable in varied conditions. The molecule goes through thousands of tests — in test tubes, animals and up to five years in sealed vaults that simulate conditions from an Alaskan winter to a Florida heat wave.

“We have to know what happens if you leave it in a car on a hot summer’s day,” said Peter Green, Pfizer’s vice president of pharmaceutical sciences in Michigan.

If the molecule passes, it moves to clinical tests where doctors across the country will give the drug to patients and record the results. And after several years of this, the drug might prove safe and effective enough to warrant an application to the FDA. Or it might not.

Pfizer’s promising new drug, Pregabalin, almost didn’t make it. In 2000, scientists found the drug was toxic in mice. Pfizer halted the development. They spent two years studying the problem, deciding it was specific to mice and safe for humans.

Now the FDA must agree. It will decide within a year.