By Karen Pihl-Carey

The FDA approved an expanded indication for Enbrel (etanercept) that will more than triple the size of the drug's market, meaning a significantly higher sales potential for Seattle-based Immunex Corp. and marketing partner Wyeth-Ayerst Laboratories.

Under the expanded label, Enbrel may be prescribed to reduce the signs and symptoms of rheumatoid arthritis (RA), as well as to delay structural damage in patients with moderately to severely active RA. It was first approved in November 1998 to treat moderately to severely active RA in patients who have an inadequate response to one or more disease-modifying anti-rheumatic drugs (DMARDs). The market size for the first indication was about 300,000 people.

"The new label, this new indication, adds about 700,000 patients," said Tim Warner, spokesman for Immunex. "So we have a total of 1 million at this point."

Sales of Enbrel were $367 million in 1999, and $131 million in the first quarter of this year. Immunex's CEO recently said he expects sales for Enbrel this year to grow 10 or 15 percent each quarter, but that estimate was under the previous label, Warner said.

Immunex's stock (NASDAQ:IMNX) jumped 13 percent on the news Wednesday, closing at $36.312.

Enbrel is a genetically engineered protein - two molecules of recombinant human tumor necrosis factor (TNF) receptor - that works by binding TNF, thus blocking its interaction with cells that respond to its signal. TNF is found at elevated levels in fluid around the joints of RA patients.

"We found through research and collaborations that TNF is a factor in many inflammatory and immune system diseases," Warner said. "And because Enbrel is the TNF receptor and effectively mops up TNF, it's able to play a role in helping to treat these diseases in a dramatic manner."

The new, expanded indication is based on data submitted in a supplemental biologics license application (BLA) in July 1999. The BLA included radiographic and clinical results from a Phase III randomized, double-blind, multi-center trial of 632 adults who had early-stage RA and had never been treated with methotrexate. (See BioWorld Today, July 16, 1999, p. 1.)

Patients in the Phase III study received either 25 mg or 10 mg of Enbrel, or up to 20 mg of methotrexate per week for one year in the form of injections or pills. The study showed that Enbrel can slow the disease's progress. Enbrel-treated patients also enjoyed a greater improvement in the signs and symptoms of RA than did the control group. (See BioWorld Today, May 12, 1999, p. 1.)

With the new, expanded indication, the label removes the restriction that largely limited Enbrel to patients who have failed therapy with DMARDs.

"This provides us an opportunity to relaunch the product," Warner told BioWorld Today. "And this is a group of people who are much younger, between 30 to 40 years old, recently diagnosed, and oftentimes still in a very confused state about being diagnosed with rheumatoid arthritis. It's not something people are really familiar with. Once they're diagnosed, the pain and the swelling and not being able to get out of bed in the morning are very disruptive. It's a brand-new audience for us."

Warner said Immunex and Wyeth-Ayerst, a division of American Home Products Corp., of Madison, N.J., will work to educate patients about the wider availability of the drug. Even though the Enbrel market now is about 1 million, about 2.5 million people in the U.S. have RA.

"A good portion of them are afraid of going on to chemotherapy, so they choose nothing, because there's really nothing else. They're afraid of the toxicities," Warner said. "With Enbrel's safety profile and the dramatic clinical response, that may change."

While Enbrel has been found to be well tolerated, its side effects include mild to moderate reactions at the injection site and headaches. Also, the FDA advisory panel that recommended the label expansion expressed some concerns about the long-term safety of the drug. Specifically, the panel was concerned about whether Enbrel increases the risk of serious infections in patients prone to infections, and whether patients receiving Enbrel are more likely to develop cancer. (See BioWorld Today, April 12, 2000, p. 1.)

"From the beginning of the development of Enbrel, we've been committed to long-term safety monitoring," Warner said, stressing the safety profile so far has been good.

Enbrel also gained an approval in May 1999 to treat children and teen-agers with moderately to severely active polyarticular-course juvenile RA. (See BioWorld Today, June 1, 1999, p. 1.)

Immunex and Wyeth-Ayerst are continuing to develop Enbrel for the other indications. The product is being tested in a large Phase III trial in chronic heart failure with 1,800 patients, and is in clinical trials in Crohn's disease, psoriatic arthritis and different types of cancer.