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More MS news articles for October 2003

A 'monstrous' drug hurdle

Pharmion to market thalidomide to Europe as cancer fighter

http://www.denverpost.com/Stories/0,1413,36~33~1667850,00.html

Wednesday, October 1, 2003
By Jennifer Beauprez
Denver Post

A Colorado company says it has found a highly effective treatment for cancer, but getting the drug to market will mean erasing the images of horrific birth defects the medication caused decades ago.
Boulder-based Pharmion Corp. is staking millions of dollars to bring thalidomide, once called "the monstrous wonder drug," back to Europe, this time to kill a form of cancer.

But the drug has a dark past, causing 10,000 to 12,000 children to be born with flipperlike limbs in the 1960s to women who took the drug to ease morning sickness.

Pharmion's chief challenge: The vast majority of those birth defects occurred in the company's two biggest markets, the United Kingdom and Germany.

"The history of this drug keeps going on and on," said Trent Stephens, an Idaho State University anatomy professor who wrote "Dark Remedy," a book on thalidomide. "It should have never seen the light of day."

Today, scientists believe the drug could help wipe out cancer, Crohn's disease, arthritis and AIDS.

Pharmion has multiple myeloma, a blood cancer, in its sights and will finance its plans with an $86.2 million initial public offering. The company Friday set a possible price of $14 to $16 per share for the stock, but as of Tuesday's market close it had not begun to trade.

Pharmion executives declined to be interviewed for this story, citing a "quiet period."

Pharmion licenses existing drugs that other companies do not want or can't afford to market. The company has licensed two other drugs besides thalidomide.

In the United States, the drug has proved to be a powerful treatment for multiple myeloma.

"It does attack cancer. It put me in remission," said Geraldine Ferraro. The former Democratic vice-presidential candidate was told she would live three years after being diagnosed with multiple myeloma in 1998.

New Jersey-based Celgene Corp. sells thalidomide in the United States on a limited basis to doctors, and there are strict rules governing the drug's use. The U.S. Food and Drug Administration has approved thalidomide only to treat leprosy but allows the "off-label use" of the drug for cancer if there is scientific data that it's a safe and effective therapy.

Pharmion licensed the European marketing rights to thalidomide from Celgene three years ago and hopes to implement similar rules for its use.

But Ferraro and others fear distribution won't be closely monitored in other countries.

"You don't have the same FDA requirements (in Europe) that you have here," Ferraro said. "I would be extremely cautious."

In 1996, 37 thalidomide babies were born in Brazil; some clinicians speculate their mothers could not read the drug labels. Some researchers also fear that men taking thalidomide may pass on the birth-defect-causing effects of the drug if they impregnate a woman.

"If a tragedy happens, we want to be sure the responsible people all take care of the victims," said Mercedes Benegbi, who runs the Thalidomide Victims Association of Canada.

Thalidomide first emerged in 1958, when drug companies raced to replicate the success of penicillin. The drug showed low toxicity in rats and acted like a sleeping pill.

But in reality, the drug did more than make people drowsy.

By 1960, German maker Chemie Grunenthal was outselling competitors 5-to-1, promoting thalidomide as a remedy for morning sickness. The United States and the Soviet Union were among the few countries that did not allow the drug's use.

The next year, babies began to be born with no arms, no ears, no legs or with short, finlike limbs. Thousands were born in Germany, where Chemie Grunenthal patented the drug.

Manufacturers recalled the drug in late 1961; England banned its use in 1962

The drug returned to medical protocols two years later, when a leprosy patient arrived at Hebrew University Hospital in Jerusalem in so much pain that he had not slept in 72 hours. His doctor found a bottle of thalidomide in a hospital storage closet and administered a dose. The patient slept for 24 hours and awoke to find his painful lesions healed.

By 1965, the World Health Organization had concluded that thalidomide's anti-inflammatory properties offered a 99 percent cure rate for leprosy, Stephens said.

Two decades later, HIV patients started importing black-market thalidomide from South America to treat AIDS-related ulcers and weight loss.

The spotlight hit thalidomide again in 1994, when research suggested the drug could stop new blood-vessel formation in cancer cells and tumors.

Today, 173 clinical trials are underway to test thalidomide's effect on myriad diseases, including rheumatoid arthritis, multiple sclerosis, Crohn's disease, lupus, HIV and tuberculosis.

Pharmion will pour $8 million into clinical trials for five kinds of cancer, including colorectal cancer, prostate cancer and renal cell carcinoma, the most common kind of kidney cancer.

Last month, Australian drug regulators approved Pharmion's bid to use thalidomide there to treat cancer. Now Pharmion is pushing regulators in a number of other countries to do the same.

The company licensed thalidomide from Celgene, but also from U.K.-based Penn Pharmaceutical. Pharmion estimates some 70,000 people in Australia and Europe suffer from multiple myeloma, and doctors diagnose 22,000 new cases there each year.

In just the past few months, Pharmion has increased its lock on selling to those patients.

Chemie Grunenthal discontinued sales of the drug in Europe. And last spring, Pharmion paid $5.5 million to buy Laphal Developpement, a French thalidomide maker that distributes the drug in France and Belgium.

In June, Pharmion also took over thalidomide sales in the United Kingdom, Ireland and Denmark after Penn Pharmaceuticals stopped distributing the drug there.

Getting past the stigma of thalidomide won't be easy.

"Twelve thousand babies in 46 countries were affected by this. I don't think many people have forgotten about that," said Mark Okafor, a doctor of pharmacy doing research at Purdue University who has followed thalidomide's development. "But if this thing should become official again, I can see so many clinicians jumping on the bandwagon again."

They did in the United States. In the first six months of this year, Celgene generated $101 million in U.S. sales, up from $119 million in all of 2002.

Despite its potential, the long-term impact of thalidomide remains unknown, Okafor said.

The drug has caused numbness in toes and fingers of many leprosy patients, which some fear may be an indication of long-term neurological complications.

"This has great potential to do good in medicine," said Okafor. "But thalidomide is still a mystery. There is so much unknown about it."

Thalidomide test

Despite concerns that it can cause birth defects, thalidomide is a powerful drug thought to be helpful in treating a variety of medical conditions. Here are some ways the drug is being used and tested:

Proven uses:

Potential uses:


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