Colour article on D2E7 -
Abbott Sees New Uses For Rheumatoid Arthritis Drug
Friday September 6
By Daniel Rosenberg, Of DOW JONES NEWSWIRES
CHICAGO - Abbott Laboratories thinks its D2E7 drug could be a blockbuster to treat rheumatoid arthritis. Now it's looking to see where else the drug might prove useful.
With D2E7 awaiting U.S. Food and Drug Administration approval for adult rheumatoid arthritis, Abbott has started trials with the drug to treat Crohn's Disease and juvenile rheumatoid arthritis.
Abbott believes D2E7's regimen may be easier for patients than Johnson & Johnson's Remicade, which the FDA approved earlier this year for long-term treatment of Crohn's - an intestinal disorder affecting 500,000 to 2 million Americans. Remicade was already approved for short-term treatment of Crohn's.
"With Remicade, you have to go to the doctor's office and get an infusion," said Dr. Steven Fischkoff, Abbott's global project head for D2E7. "With D2E7, you can take it at home." D2E7 is injected by the patient.
Crohn's disease is a chronic inflammatory bowel disorder that commonly affects the lower part of the small intestine and the large intestine, and usually appears during late childhood or early adulthood. Symptoms include diarrhea, cramping, dehydration, infection, malnutrition and abdominal pain. In severe cases, it produces holes in the skin, called fistulae, which are deep ulcer tracts that have eaten through the intestines.
Remicade and D2E7 are similar in that both block the activity of tumor necrosis factor alpha (TNF-alpha), which plays a central role in the inflammatory responses of many autoimmune diseases such as rheumatoid arthritis and Crohn's. However, D2E7 is different from Remicade in that it's the first fully human monoclonal antibody to be developed. Fully human monoclonal antibodies have a protein structure that makes them essentially indistinguishable from antibodies present in the human body.
"The expectation is, because the antibody looks like any other, the body may form less of an immediate reaction to it," Fischkoff said.
Patients on Remicade frequently must take other drugs to prevent the formation of antibodies caused by Remicade, Fischkoff said. One such drug is methotrexate, which can cause symptoms such as nausea and hair loss. Drugs like this wouldn't be necessary for patients taking D2E7.
Trials with Remicade showed that inhibiting TNF-alpha can help Crohn's sufferers. In a 54-week study involving 545 Crohn's patients, 57% of patients treated with Remicade responded within two weeks of treatment. The drug is the first therapy that can both induce and maintain remission-level control of disease symptoms in many cases, said Dr. Gary Lichtenstein, associate professor of medicine and director of the Center for Inflammatory Bowel Diseases at the Hospital of the University of Pennsylvania.
An infusion of Remicade, done intravenously, can take several hours, meaning a Crohn's patient can lose half a day. Although treatment varies, a number of Crohn's patients interviewed said they get an infusion every eight weeks or so.
Abbott is studying a number of different treatment regimens for Crohn's patients in its D2E7 trial, including once every two weeks - the schedule for rheumatoid arthritis patients. Abbott has initiated a Phase II/III study for Crohn's patients, who will be randomly selected to receive D2E7 or a placebo.
Challenge To Switch Patients
It remains to be seen if D2E7 will work as well as Remicade. If it does, it's unclear whether patients and doctors will gravitate toward it and away from Remicade.
One doctor told a Crohn's patient that he would recommend keeping her on Remicade as long as it worked, and not switching her to anything else, the patient said, requesting anonymity. The doctor couldn't be reached for comment.
"He said if you're already in remission and (Remicade) is working, he wouldn't recommend anyone changing," the patient said. "I am now in remission because of Remicade."
Another Crohn's patient, who's had the disease for 40 years, said Remicade is the first drug that put her into remission.
"Remicade is a miracle drug, an absolute miracle drug," said the patient, who also requested anonymity.
She said every eight weeks she goes to a cancer center, where she gets infused with Remicade. The procedure lasts about five hours and can cause back pain and flu-like symptoms. Although five hours is a heavy time commitment, she doesn't mind "giving up the day."
Her success with Remicade doesn't mean she wouldn't give D2E7 a try if it ever becomes available.
"If I could do an injection at home and get the same response - hey, I'd do it," she said.
Some patients report that Remicade, after working for a while, loses its effectiveness.
"(Remicade) really turned me around for a while, and I credit it for allowing me to work a couple of years more," said another patient, again speaking on the condition of anonymity. "Now, however, I have flared despite the Remicade, and I can no longer work."
Remicade for Crohn's patients costs about $10,000 to $12,000 a year. It is covered by most insurance plans and by Medicare and Medicaid.
Ron Schmid, a spokesman for Centocor, the Johnson & Johnson subsidiary that makes Remicade, said infusion is a smart way for patients to receive the drug. It gives them the opportunity to connect with their health-care provider, the drug is given under supervision and patients can be watched more closely for side effects.
Abbott officials say they don't know how long it will be before the company could submit trial results from Crohn's patients on D2E7 to the FDA, and so it looks like Johnson & Johnson doesn't have to worry about competition in the near future.
Abbott also just started trials of D2E7 for juvenile rheumatoid arthritis sufferers. Juvenile rheumatoid arthritis is a chronic autoimmune disorder that affects 100,000 children in the U.S., ultimately damaging joints by eroding bones and cartilage. It can cause intense pain and leave young patients unable to perform daily activities. There is no cure.
Patients today are prescribed non-steroidal anti-inflammatory drugs to reduce stiffness and pain, as well as corticosteroids to reduce inflammation. Other therapies are also available. A common drug prescribed for juvenile rheumatoid arthritis is Enbrel, made by Immunex Corp. (NasdaqNM:AMGN - News), a company recently acquired by Amgen Inc. .
D2E7 will be studied in a randomized, multi-center PHASE III clinical trial to assess its safety and efficacy in juvenile arthritis patients, Abbott said.
"We've seen tremendous advances in the treatment of adult RA, and studies in pediatric patients are critical to understanding the potential use of new treatments in children, who are fighting destructive symptoms at a much younger age," said Dr. Daniel Lovell, professor of pediatrics at Cincinnati Children's Hospital Medical Center, and chairman of the Pediatric Rheumatology Study Group.
Fischkoff, of Abbott, said children treated with D2E7 would need fewer injections than they do with Enbrel... |
