Drugs in Testing Show Promise for Lupus
by Heather Won Tesoriero

New Treatments Target Disease, Not Just Symptoms; First Big Advances in 50 Years

The last time a new drug was approved to treat lupus, a serious autoimmune disorder that afflicts an estimated 1.5 million Americans, Dwight D. Eisenhower was president. But after a 50-year stretch without a major advance, there are finally some promising treatments on the horizon.

Several drug makers are in advanced-stage trials for lupus drugs. Human Genome Sciences, Inc. will begin enrolling patients in the next two weeks in the largest ever late-stage lupus trial, following positive results in earlier testing. Bristol-Myers Squibb Co. is conducting lupus trials on Orencia, its rheumatoid arthritis drug, and Genentech, Inc. and Biogen Idec, Inc. are conducting late-stage trials on Rituxan, a cancer drug that has been used off-label for lupus.

This is welcome news for lupus sufferers, 90% of whom are women who experience onset of the disorder between the ages of 15 and 40. A chronic inflammatory disease that can affect almost any part of the body, lupus produces complications ranging from serious skin rashes and joint pain to organ malfunction and atherosclerosis, or hardening of the arteries. This condition can be life threatening--the most common causes of death are heart attacks and strokes.

For many years, lupus wasn’t well understood by doctors, and can still be difficult to diagnose. There has been no drug that targets the disease itself, and doctors have been able to treat only complications.

“Part of the reason why lupus remains challenging and mysterious to people is because it doesn’t fit the classic disease paradigm,” says S. Sam Lim, an Emory University rheumatologist who head up a federally funded lupus patient registry. “There isn’t one clinical feature or symptom.”

To treat symptoms, doctors have worked from a stable of old medicines. Steroids and immunosuppressants, drugs that shut down the body’s natural defenses and that can provide relief to patients, are the most commonly used. There are often significant side effects, including an impaired immune system, opening patients up to infections, and weight gain, which prompts other problems.

Doctors have also turned to a number of medications that are approved for other conditions. They are allowed to prescribe any approved medicine for uses beyond those contained on the label, but patients can have difficulty getting insurance coverage for such off-label drugs.

A lot of lupus patients take several medications for their symptoms but long for a drug that would actually target the disease as opposed to the symptoms. It seems increasingly possible that lupus patients will soon get their wish.

With the lack of remedies for the disorder, the government began investing more heavily in lupus research and now spends roughly $89 million a year on the disease. As results emerged, doctors and researchers saw clues into how lupus works in the body’s cells. While no reliable numbers on growth exist, experts agree the lupus population has expanded along with better diagnoses. In turn, some drug companies  have begun to pay more attention to the disorder.

“Drug companies weren’t interested in it because they thought it was a small market,” Gary Gilkeson, head of the medical and scientific board of the Lupus Foundation of America, said “They realized that was wrong.” By one estimate, the lupus drug market, which was $300 million in 2005, could reach $1.3 billion in 2015 if the potential treatments prove to be efficacious.

There’s now a horserace among a few drug companies to be the first one in 50 years to gain approval to make and market a lupus drug. There are currently four drugs in late-stage lupus trials, as well as two being tested for lupus nephritis. Most of these drugs are monoclonal antibodies, which attempt to target the cells that contribute to the damaging antibodies. Early results for a trial for Lymphostat-B, a collaboration between Human Genomone Sciences and GalxoSmithKline, PLC, showed to reduce lupus disease activity. Now, the new international trial will enroll more than 1,600 patients to try to confirm the findings.

Bristol Myers is conducting late-stage lupus nephritis trials. Biogen Idec is going ahead with plans to test Rituxan, a blockbuster cancer and rheumatoid arthritis drug, in lupus patients, both with and without lupus nephritis. The lupus trial will enroll 250 patients and the nephritis trial will enroll 140. The FDA issued a warning following two deaths from a viral infection of lupus patients using the drug off-label. Doctors and analysts took heed, but say that they’re still hopeful that the drug will be approved, noting that because lupus patients have compromised immune systems, it’s impossible to determine whether Rituxan was responsible.

Aspreva Pharmaceuticals, Corp. is testing anti-organ rejection treatment CellCept for lupus nephritis. CellCept, a drug for organ transplant recipients, is often prescribed off-label to lupus patients. Results from the first phase of its late-stage trials are expected this year.

There have been more setbacks in the research. In 2003, La Jolla Pharmaceuticals, Inc., which is developing the drug Riquent to treat lupus nephritis, found that its drug wasn’t sufficiently effective. The company is taking another crack, this time increasing the doses. La Jolla has a special protocol assessment from the Food and Drug Administration, meaning that if its revamped trials reach specified outcomes, the drug will be approved. The results of the current trials are likely a couple of years away, but many patients are eager to enroll in the trials.

IN THE PIPELINE
Some medications being studied for the treatment of lupus

Drug & Maker	How It Works	Status
Lymphostat-B Human Genome Sciences, Inc. and GalxoSmithKline, PLC	An antibody given by injection. Phase II tests in more than 400 patients showed the drug, when compared to placebo, significantly lowered disease activity.	Company expects to begin Phase III trials early this year.
Orencia Bristol-Myers Squibb Co.	Works by blocking the full activation of some T-cells, soldiers in the body’s response to invaders.	Approved to treat rheumatoid arthritis. In Phase II trials for lupus.
Rituxan Genentech, Inc. and Biogen Idec, Inc.	Selectively depletes some of the body’s B-cells, white blood cells that produce antibodies.	Approved for non-Hodgkin’s lymphoma and rheumatoid arthritis; the companies are conducting two large tests of Rituxan in lupus.

Article prepared by Heather Won Tesoriero,   Source: WSJ.com