By Randall Osborne
West Coast Editor
SAN FRANCISCO ¿ A ¿migration of mentality¿ among specialists, who are increasingly accepting antitumor necrosis factor drugs and acknowledging the nature of rheumatoid arthritis, is changing the field of treatment, said Dan Burge, vice president of clinical research for Seattle-based Immunex Corp.
¿A couple of years ago, when we were first launching anti-TNF therapies, they were a curiosity,¿ Burge told BioWorld Today at the 65th annual scientific meeting of the American College of Rheumatology.
Immunex¿s flagship Enbrel is one anti-TNF drug for RA; the other is Malvern, Pa.-based Centocor Inc.¿s Remicade (infliximab).
¿We have new data [released at the meeting] that¿s an extension of the longer-term efficacy and safety data, showing durability of response over five years,¿ Burge said.
¿In our clinical trials, we¿ve seen no greater [infection] risk with Enbrel compared to placebo, without any background therapy or with background methotrexate,¿ he added, noting that people are getting a little tired of hearing about it.
¿If you talk to rheumatologists, a lot of them look at the long-term data and say, Yes, this is great, this is very reassuring, next question,¿¿ Burge said. ¿Another year has gone by, people have done well, and there haven¿t been any big issues.¿
Regarding the infection findings, he allowed, ¿you don¿t really have a true capture of all the adverse events in your post-marketing data, but the reporting rate is substantially less than what we would expect, and it reflects where we think it should be.¿
Previous research has shown about 9.5 infections requiring hospitalizations or intravenous antibiotics per 100 patients per year.
¿All the data is pre-anti-TNF therapies,¿ he said, noting that, with Enbrel, the rate is four to five incidents per 100 patients per year.
The FDA approved Enbrel first in November 1998 for use in patients with moderate to severe RA who have not responded well to other disease-modifying anti-rheumatic drugs, also granting a label to indicate Enbrel may be used in combination with the most widely used DMARD, methotrexate.
Immunex has been pursuing label expansions ever since. At the ACR meeting, posters have dealt with Enbrel for psoriatic arthritis (positive in a Phase III study) and ankylosing spondylitis (positive in Phase II).
¿The only thing that¿s been shown to be clearly an issue with Enbrel is injection site reactions, which are pretty much nothing,¿ Burge said. ¿Continually, with anti-TNFs, people have been concerned about malignancies, and there haven¿t been any of those issues with Enbrel.¿
Another, somewhat less urgent concern has been over autoimmune effects, some of which have surfaced in experiments with Remicade.
¿We really haven¿t seen a bunch of lupus cases in our data,¿ Burge said. ¿There have been some with one of the other products, which has increased the concern, [with scientists saying,] If you see it in one, let¿s look at the others.¿¿
Further on the positive side, researchers have found six weeks of work can be saved by RA patients who begin doses of Enbrel when their disease manifests.
¿That was the difference between somebody starting Enbrel now, or two years later,¿ Burge said.
¿The old adage was that 50 percent of patients had erosive disease by two years,¿ he added. ¿People are rethinking that. It¿s much more aggressive.¿ Radiographic studies, including one by Immunex with 600 patients, have been helpful, he said.
¿RA patients are some of the toughest people I¿ve ever met,¿ said Burge, who is a medical doctor. ¿They¿re able to deal with challenges that you and I take for granted. If their hands are deformed and they can barely hold things, they just function in life without assistance. On the other hand, they have this very severe problem that hits hard and early.¿
Anti-TNF therapies make up a strong enough presence in the RA field that the Arthritis Foundation earlier this month issued a paper, in which the foundation said it sees ¿great promise¿ in them ¿ although many are making comparisons between Enbrel and trial data from tests with Amgen Inc.¿s investigational agent Kineret, an IL-1 receptor antagonist. Burge takes the comparisons in stride.
¿You take the new product and compare it to the market leader,¿ he said. Immunex¿s stock (NASDAQ:IMNX) closed Tuesday at $26.55, up $1.01.
The ACR meeting, for which about 7,000 attendees had pre-registered, continues through Thursday.
In other news from the meeting:
¿ Centocor Inc., of Malvern, Pa., said 82 abstracts are being presented involving treatment across a range of diseases with Remicade (infliximab), a monoclonal antibody that specifically targets and irreversibly binds to TNF-alpha on the cell membrane and in the blood. A randomized, double-blind, placebo-controlled study in 40 patients with active spondyloarthropathy showed that at 12 weeks, patient and physician global assessment improved in the infliximab group, while no improvements were seen in placebo patients. A second study looked at infliximab for ankylosing spondylitis in a placebo-controlled, multicenter trial of 70 patients. At week 12, based on the primary endpoint that defines response as a 50 percent improvement on a disease activity index, 53 percent of patients who received infliximab responded vs. 9 percent of patients receiving placebo.