By Lisa Seachrist
The FDA approved Immunex Corp.'s Enbrel (etanercept) for use as a therapy for children and teenagers with moderate to severe polyarticular-course juvenile rheumatoid arthritis (RA).
This is the first label expansion for the drug, approved in November 1998 for use in moderate to severe RA patients not responding to disease-modifying anti-rheumatic drugs, such as methotrexate. Seattle-based Immunex plans to file for an additional indication in early active RA in the third quarter of 1999.
"Polyarticular-course arthritis is the most common form of [juvenile] RA," said Tim Warner, spokesman for Immunex. "Before Enbrel, these kids were treated with methotrexate and steroids, which have terrible side effects."
An injectable, genetically engineered protein - two molecules of recombinant human tumor necrosis factor (TNF) receptor - Enbrel works by binding TNF and blocking its interactions with cells that respond to its signal, with the result of damage to tissues. TNF is found at elevated levels in the fluid surrounding the joints of RA patients.
Immunex filed its supplemental application for juvenile RA based on a study of 69 patients immediately after the first approval in November. Participants in that study ranged in age from 4 to 17 years and had proven refractory to or intolerant of methotrexate therapy.
The trial was a two-part study. The first three months of the study, all of the children received Enbrel injections twice a week at a dosage of 0.4 milligram per kilogram of body weight. The second phase of the study, which lasted for 4 months, had half of the patients on Enbrel and half on placebo.
Seventy-four percent of the patients showed improvement during the first phase of the study. In the second part of the study, only six of the 25 patients remaining on Enbrel experienced a disease flare, whereas 20 out of 26 placebo patients experienced a flare.
"We were very pleased with the results of this trial," Warner said. "There was a very clean safety profile for this trial and strong efficacy data. The FDA helped us design this trial, and it was a really positive relationship."
Except for injection-site reactions, which occurred in about 20 percent of all patients, Enbrel had no more adverse events associated with it than placebo. Warner, however, was careful to point out that Enbrel was not indicated in patients who have infections or develop infections while taking the drug.
"We are working very hard to make sure that the right patients are using Enbrel," Warner said.
There have been reports of infections that have led to serious problems, including fatalities, since the product was approved.
Mike King, at BancBoston Robertson Stephens Inc. in New York, told BioWorld Today, that the size of the juvenile RA market is not the most important thing about the FDA's approval.
"It's small," he said, estimating the number of juvenile RA cases in the U.S. at about 70,000. "The issue with the approval is that it should alleviate concerns there is any lingering worry at the FDA there is toxicity associated with Enbrel use. Can you imagine a worse public-relations disaster than having a bunch of teenagers die, or kids? Forget it, your career's over. The issue is whether or not it's safe for kids."
Immunex is also testing Enbrel as a treatment for chronic heart failure in a Phase II/III study. Earlier research has shown an association between elevated TNF levels and chronic heart failure. The company is expecting results in the first half of 2001.
Enbrel is co-marketed with Wyeth-Ayerst Laboratories, a division of American Home Products Corp., based in Madison, N.J.
Immunex's stock (NASDAQ:IMNX) closed Friday at $131.25, down $0.437.