By Mary Welch
Immunex Corp. filed a supplemental biologics license application for Enbrel seeking a broader label that could significantly increase its market in the treatment of rheumatoid arthritis.
The Seattle-based company is seeking an approval for an indication that shows Enbrel slows structural damage and improves the signs and symptoms of early, active disease.
The new filing is based on a recently completed Phase III study, the results of which were disclosed in May. That trial included 633 rheumatoid arthritis (RA) patients who had suffered from the disease for less than three years and had never been treated with methotrexate, a disease-modifying antirheumatic drug.
"The trial and this filing, if approved, should make Enbrel the standard care for rheumatoid arthritis," said Tim Warner, director of communications for Immunex. "It is becoming more accepted to aggressively treat early, active RA. Enbrel is the driving force behind this new thinking."
The study, using joint X-rays, proved Enbrel (etanercept) could slow the progression of joint damage that often is a consequence of RA. In addition, patients receiving Enbrel had greater improvement in the signs and symptoms of RA than with the control therapy. (See BioWorld Today, May 12, 1999, p. 1.)
Enbrel was found to be well tolerated, with the most common side effect being mild to moderate reactions at the injection site.
Immunex estimated the patient population for this new indication could be 1 million, though it said the actual number of sufferers could be as high as 2.5 million.
"A significant portion of the population doesn't even seek treatment because too many of the alternative treatments are unacceptable," Warner said. "They just didn't want to have mouth ulcers, hair loss and other side effects that occur with the traditional therapies. Enbrel doesn't have any of those side effects."
The name "early rheumatoid arthritis" may be confusing, Warner said. "Most people believe that in early RA the person just got the disease and that moderate to severe arthritis is when there are a lot of symptoms. But that is actually incorrect. People with early-stage RA are just as ill as those with moderate or severe disease. It's more how long they've been diagnosed and what type of drugs they have had rather than the severity of the disease."
The trial answered many outstanding questions concerning rheumatoid arthritis, Warner said.
"Scientists asked whether the disease can be slowed down, and we weren't surprised, but the study showed that Enbrel can slow the disease's progress. It showed that passively treating the disease with an unaggressive therapy doesn't work and that Enbrel is bucking the trend by being very aggressive."
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.
Enbrel was approved and launched in November to treat moderate to severe RA that has not responded well to other treatments. The drug also was approved to be used with methotrexate. In May, the FDA included children and teen-agers (aged 4 through 17) in the indication for the treatment of moderately to severely active polyarticular-course juvenile rheumatoid arthritis. (See BioWorld Today, Nov. 3, 1998, p. 1; and June 1, 1999, p. 1.)
In the fourth quarter of 1998, the first quarter it was on the market, Enbrel racked up sales of $12.7 million. For the first quarter of 1999, sales were $60 million. The company won't release second-quarter sales figures until Tuesday but Warner estimated them around $80 million.
So far, the FDA has not indicated whether it would designate this licensing application for priority review, Warner said. Even if it doesn't, he said the FDA decision would be expected within a year.
Immunex intends to pursue other indications for Enbrel, including chronic heart failure, a form of heart disease resulting from damage by conditions such as high blood pressure, a heart attack or poor blood supply.
It is in a Phase II/III trial for that indication, with results anticipated by the first half of 2001. (See BioWorld Today, March 9, 1999, p. 1.)
Enbrel is co-marketed by Wyeth-Ayerst Laboratories, a division of American Home Products Corp., of Madison, N.J. Immunex's stock (NASDAQ:IMNX) closed Thursday at $125, up $5.75.