Leukine: moving in a new direction

Dr. Mark Gilbert and his colleagues have careers staked on Leukine, the first drug to emerge from Seattle biotechnology, a product that many believe has never reached its full potential.

Stressful as that was at Immunex, tensions amplified a year ago when California-based Amgen bought Immunex, then had to sell Leukine to satisfy anti-trust regulators.

About 200 people who worked on Leukine in Seattle figured their jobs could vanish, or be shipped to a stodgy pharmaceutical giant in New Jersey.

But it didn't turn out that way. Gilbert still has a job — a promotion, actually — his co-workers are the same, and he didn't have to call the movers. Lately, he's been wearing a fleece vest that reads "Berlex Oncology."

"We know where we're going, we're at Berlex, we're developing molecules and we'll be here in Seattle," said Gilbert, Berlex's executive director of clinical development and operations. "That confidence is not necessarily enjoyed by some of our former colleagues."

The new direction for Leukine and the people who work on it took shape last spring. That's when a German pharmaceutical company Schering and its U.S. division, Berlex Laboratories, sent people to visit Seattle.

The group looked hard at Leukine, a genetically engineered protein that in 1991 became Immunex's first approved drug. Leukine stimulates the immune system to grow infection-fighting white blood cells.

They saw potential for it to attack tumors and a common intestinal problem, rather than just alleviate side effects of chemotherapy. Berlex paid $380 million in cash for it.

Over the summer, Berlex promised to follow through on Immunex's goals to boost use of Leukine, to hire most of its workers and keep them in Seattle and Bothell. It was a bold commitment for a drug that was outsold by its competitor, Amgen's Neupogen, by a 12-to-1 margin in the previous year.

Both drugs have a long history, being approved by the Food and Drug Administration (FDA) in 1991, but only Neupogen became the cash cow drug companies lust after. Leukine took a decade to crack $100 million in annual sales.

"Berlex explained to us how it was beneficial for them as a business to keep things here in Seattle, but I'll be honest, none of us believed them," Gilbert said. "But they convinced us."

Six months later, Berlex appears to be keeping its word. It has hired 174 of about 200 former Immunexers who worked on Leukine or in support positions and kept 153 in Seattle and Bothell.

Last summer, top Berlex managers toasted their future in Puget Sound at dinner at Cascadia Restaurant and treated new employees to flowers on their desks the first day. Berlex matched or beat Immunex salaries and benefits, down to the bus passes. Schering recently made Fortune magazine's list of 10 best companies to work for in Europe.

For a global company with 25,000 employees and major research-and-development centers in Europe, Japan and the United States, Leukine could have gone elsewhere. Instead, Berlex gave the Seattle operation more authority to oversee research and development for its cancer drugs.

"There's a level of expertise those individuals in Puget Sound have that we recognize and we didn't want to jeopardize," said Pat Johnson, director of human-resource systems for Berlex in Montville, N.J.

Susan Erb, a former Immunex vice president who helped negotiate the Leukine sale, said Berlex won because it had done the most methodical homework and was considered stable and committed. She called it a good sign that Berlex is trying to raise its profile in the community.

"Companies who aren't going to do what they say they're going to do usually try to keep a low profile," Erb said.

So far, Berlex is running clinical tests to show Leukine's benefits in skin cancer, leukemia and for some more painful side effects of chemotherapy. Many of the trials were started in the mid-1990s by Immunex, without going all the way to FDA approval.

This time, Berlex is investigating Leukine's prospects in a trial in Crohn's disease, a painful inflammation of the intestines. Preliminary plans are being made to outfit part of the Bothell plant to manufacture Leukine.

Whether Bothell will have to start mass-producing more depends on a 120-patient clinical trial in Crohn's. It could be a risky bet, because patients with Crohn's have overzealous inflammation digging into their intestines, a response to invaders like bacteria. Since Leukine stimulates a type of inflammation, in theory, it could throw fuel on the fire.

But Gilbert said researchers now believe Leukine's brand of inflammation appears to wipe out intestinal invaders before an even more destructive level of inflammation kicks in. A small trial of 15 patients showed eight were in remission after treatment.

If results can be matched in more patients — always an uncertainty — Leukine could offer an advantage for a disease that afflicts up to 1 million Americans, according to the Crohn's and Colitis Foundation of America.

Since it is painful, chronic and widespread, pharmaceutical companies are racing to develop new inflammatory-bowel treatments as moneymakers. Whether Leukine rises to that level depends on clinical results, due this summer.

"If we have a positive trial in Crohn's, that will make some positive change in Seattle," Gilbert said.

Luke Timmerman: 206-515-5644 or ltimmerman@seattletimes.com.

Berlex Laboratories

What it is: The U.S. wing of Schering, a global pharmaceutical company based in Germany.

Founded: Berlex, 1979; Schering, 1871.

Employees: Berlex has 153 workers in Seattle and Bothell, part of Schering's 25,000 workers worldwide.

Schering's global reach:

2001 sales: $5.1 billion

2001 profit: $441 million

2001 R&D spending: $911 million

What it sells: Birth-control pills, drugs for multiple sclerosis and cancer and diagnostic-imaging materials, among others.

How it came to Puget Sound: Last May, it bought Immunex's Leukine for $380 million. Leukine spurs growth of infection-fighting white blood cells that have been knocked out by chemotherapy. Berlex says it is continuing Immunex's tests of Leukine as a cancer fighter on its own, and as a treatment for Crohn's disease, an inflammation of the large intestine.

Sources: Schering, Berlex


Leukine sales

2001 $108.4 million

2000 88.3 million

1999 69.1 million

1998 63.8 million

Source: Immunex reports