One Drug, Many Uses. Good Idea?

Posted on Jul 1, 2008 in Health & Wellness

By John Russell in the Indy Star

Feeling depressed? Ask your doctor about Cymbalta.

Growing anxious? Ask about Cymbalta for that, too.

Do you have diabetes nerve pain? Fibromyalgia? Cymbalta is approved for those conditions as well. In Europe, you can use the drug, marketed under a different name, to treat stress urinary incontinence.

Cymbalta, launched in 2004 as an antidepressant, is quickly becoming the Swiss Army knife of drugs. With less than four years on the market, it is racking up one government approval after another, and generating billions of dollars for Indianapolis drugmaker Eli Lilly and Co.

And Lilly isn’t done. It recently asked the Food and Drug Administration to allow the use of Cymbalta for chronic knee and low back pain. Meanwhile, scientists are testing Cymbalta for treatment of chronic fatigue, yet the drug has been linked to increased risk of suicide among people younger than 25.

How one drug can treat so many ailments illustrates how pharmaceutical companies — under pressure from rising research costs and bracing for more generic competition — are pushing hard to find every possible use for their existing drugs.

“The first and foremost thing a drug company wants to do is find new uses for existing drugs,” said Steven Findlay, a health-care analyst at Consumers Union and managing editor of Consumer Reports Best Buy Drugs. “If you can expand a drug into another market, you stand to make a lot of money.”

Expanding the use of Cymbalta also shows how Lilly is working aggressively to shore up its revenue base. Many of the company’s top drugs will lose patent protection beginning in 2011. Those drugs, and their billions of dollars worth of sales, support Lilly’s campus of labs and offices south of Downtown, home to 12,000 workers.

Across the industry, pharmaceutical companies are having trouble getting new medicines out of their research labs. Last year, the FDA approved 19 new drugs, the fewest in 24 years. Lilly hasn’t launched a new drug for humans in three years.

“The question you have to ask is, are drug companies using all their scientists to look at new uses for drugs they already have, at the expense of developing new drugs?” said Dr. Lon Castle, senior director for medical and analytical affairs at Medco Health Solutions of New Jersey, one of the nation’s largest drug distribution companies.

Lilly says it is not resting on its laurels. The company’s scientists are developing new drugs for a wide array of diseases, including cancer and multiple sclerosis. In May, the company dedicated the final phase of its $1 billion biotechnology complex, where scientists will research the next generation of biopharmaceuticals for such conditions as diabetes and Alzheimer’s disease.

But analysts say it remains to be seen whether Lilly can launch promising new drugs before losing patents on existing top sellers. In the past year or so, several of its late-stage drugs have been shelved, including an inhaled insulin and a drug for treating eye diseases. Last week, the company’s most critical experimental drug, a blood thinner called prasugrel, was delayed for three months at the FDA’s request.

In the meantime, the trend of finding new uses for old drugs continues at full force. Amgen’s Enbrel, for example, is approved for rheumatoid arthritis, psoriasis and a chronic spinal pain condition known as Ankylosing spondylitis. The drug also is being researched for dozens of additional uses, including Alzheimer’s disease and vasculitis. Pfizer’s pain pill Lyrica is approved for three separate conditions of the nervous system, and the company plans to seek approval for the drug to treat epilepsy.

“This may speak to the desperation of companies to eke out any and all possible indications from existing drugs, rather than invest big bucks in the search for truly novel entities,” said Dr. Daniel Carlat, a Massachusetts psychiatrist and frequent industry critic.

Multiple uses are good, some say

Yet others look at the same picture and say drug companies are doing the right thing: using scientific knowledge to broaden the use of existing drugs. It’s legal to market a drug for more than one condition, as long as drugmakers get FDA approval, a process that requires submitting clinical proof that the drug is safe and effective for each condition.

“I think it’s kind of remarkable that some drugs can be effective for many different things,” said Kevin Outterson, director of the health law program at the Boston University School of Law. “There’s nothing wrong at all with a company going through the studies and showing the FDA there’s another thing the drug can be used for, and getting it added to the label.”

Certainly, the practice of using one pill for numerous ailments has a long history. Aspirin, for example, has become the workhorse of the medicine chest, used by millions of people for such diverse needs as reducing inflammation, treating a fever, relieving pain and preventing heart trouble.

But the stakes are high for a drug such as Cymbalta, which carries significant risks. Like all antidepressants, the drug has a black-box warning that it may increase the risk of suicide in people younger than 25. In 2004, a 19-year-old drug-testing volunteer, Traci Johnson, hanged herself in the Lilly Clinic in Indianapolis while participating in clinical trials for Cymbalta.

The drug also carries a long list of possible side effects, from nausea and dry mouth to fatigue and constipation.

“I think the question is, should one drug compound do so much?” said Shannon Brownlee, author of “Overtreated: Why Too Much Medicine Is Making Us Sicker and Poorer.”

“This is a drug that may have a really serious side effect called suicide,” Brownlee said. “Don’t we have other drugs available that are safer and just as effective for such things as the management of chronic knee and low back pain?”

But Lilly hasn’t been shy about promoting the drug. Last year, the company spent $183.3 million on direct-to-consumer advertising for Cymbalta, promoting its use for depression and pain, according to Nielsen Monitor-Plus. That made Cymbalta No. 3 in the nation in ad spending, behind insomnia drugs Lunesta, made by Sepracor, and Ambien CR, made by Sanofi-Aventis.

The commercials, which are still running, are designed to make Cymbalta a household name on par with Prozac, an older antidepressant and Lilly’s top-selling drug before its patent expired in 2001.

The ad blitz has helped catapult Cymbalta to second place in sales among all Lilly drugs, ringing up sales of $2.1 billion last year, up 60 percent.

Analysts expect Cymbalta to continue growing. Catherine Arnold, a drug analyst with Credit Suisse in New York, predicts Cymbalta sales will hit $4 billion by 2012, putting it in first place among Lilly drugs.

Other analysts agree Cymbalta is a strong engine that could drive Lilly’s fortunes for years to come.

“From a business point of view, it’s a great thing,” said Les Funtleyder, a drug industry analyst for Miller Tabak & Co. in New York. “If you have the asset, you might as well use it. But scientifically and medically, it depends, because the farther you move a drug away from its original indication, and the wider the population you have taking a drug, the greater the chance some rare side effect will pop up.”

The link between pain and mood

Lilly says Cymbalta is able to do so much because pain and mood — the drug’s approved uses — are thought to be closely connected.

Cymbalta increases activity in two chemicals in the brain: serotonin and norepinephrine. They occur naturally and regulate mood. But Lilly says chemicals also play a role in communicating pain to the brain.

“All pain travels through the body and into the brain,” said Dr. Michael Robinson, a Lilly psychiatrist and associate medical director of Cymbalta. “In order for someone to experience pain, it’s perceived by the brain. Cymbalta is a medication that works in the brain and spinal cord. Based on its mechanism of action, it’s effective in a number of disorders.”

Lilly says some pain protects the body, such as the pain you would feel when touching a stove. But other pain, called “bad pain,” has no protective function and sometimes no known causes.

“The bad pain serves no purpose,” said Dr. Amy Chappell, a neurologist and Lilly medical fellow. “It’s nonphysiological pain that causes lots of unnecessary suffering. All the pains we’ve studied (for Cymbalta) fall into this category. They’re all related and, we think, are treatable.”

Some outside drug experts agree. Craig Svensson, dean of Purdue University’s College of Pharmacy, Nursing and Health Science, said some drugs are known to work across many diseases that seem unrelated, including different types of pain.

“The drugs may have some commonalities in the way you manage that pain, even though what initiates that pain or the underlying disease is different,” he said.

The problem with subjective ailments

But how well drugs treat pain and mood is a controversial topic. Such ailments are highly subjective. Doctors have no objective tests, such as X-rays or blood tests, to measure pain or any kind of psychiatric illness. Instead, they have to rely on their patients to describe their symptoms.

And some physicians and researchers question whether fibromyalgia, the latest ailment treated by Cymbalta, is even a genuine disease. An estimated 5 million people, mostly women, are affected with it, according to the Centers for Disease Control and Prevention.

“A lot of doctors deny the existence of fibromyalgia,” said Dr. Marcia Angell, former editor-in-chief of the New England Journal of Medicine. “It certainly cannot be reproducibly diagnosed because so many of the criteria are subjective. So you have a subjective diagnosis and a subjective outcome. You don’t know whether the treatment has worked or not. . . . It’s such a lucrative business, because you can create the disease.”

But Lilly defends its use of Cymbalta for pain and mood disorders, calling the drug an important treatment option. And some experts say drug companies are doing what they are supposed to do: Find ways to treat diseases, regardless of the age of the drug.

“Drug companies are certainly facing a tough economic environment right now,” said Joseph DiMasi, director of economic analysis at the Tufts Center for the Study of Drug Development in Boston. “Maybe you can argue it’s more profitable to concentrate on finding new treatments for old drugs. But a good treatment is a good treatment, regardless of whether the drug is new or old.”