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 percent 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. The condition can be life threatening: The most common cause of death is 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 only treat 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 heads up a federally funded lupus patient registry. "There isn't one clinical feature or symptom."
Keri Farmer, 28, a pediatric medical resident in Cleveland, Ohio, was diagnosed with lupus five years ago while in medical school. She experienced severe joint pain, swelling and fatigue and was tested for a host of illnesses. While doctors eventually concluded she had some type of autoimmune disorder, she went a year without a specific diagnosis. It wasn't until about a year and half later, when she came down with lupus nephritis, a kidney disorder that occurs in roughly half of lupus patients, that doctors concluded she had lupus.
To treat symptoms, doctors have worked off a stable of old medicines. Steroids and immunosuppressants, drugs that shut down the body's natural defenses and that can provide some 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. Doctors 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 treatments.
To manage her lupus symptoms, Dr. Farmer now takes seven medications, which include a drug for high blood pressure (another common complication), a steroid and a medication for her rashes. "I would love for there to be a drug that would actually target the disease as opposed to the symptoms," she says.
It seems increasingly possible that she will get her 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. And, while no reliable numbers on growth exist -- a deficit Dr. Lim's patient registry aims to fill -- experts agree the lupus population has expanded along with better diagnoses. In turn, some drug companies began 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, says. "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 Genome Sciences and GlaxoSmithKline PLC, showed to reduce lupus disease activity. Now, the new international trial will enroll more than 1,600 patients to try and confirm the findings.
Bristol-Myers is conducting late-stage trials with Orencia, its rheumatoid arthritis drug that came out in the U.S. last year, to see if it helps lupus patients. The international trial will enroll 180 to 190 patients. Orencia, which is administered about every 28 days via a 30-minute intravenous infusion, targets T-cells, which are believed to have a major hand in inflammation.
And Genentech in collaboration with 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. Last month, 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 some 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's 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. Jeri Brown, 60, of Durham, N.C., has suffered from lupus for over 15 years and has taken steroids on and off. Last year, she was enrolled in a trial for epratuzumab, which is being developed as a potential lupus treatment by Belgian company UCB. Though Ms. Brown doesn't know whether she received the actual drug or a placebo, she says she's had full relief from her joint pain and swelling, which at times was so severe, she had trouble getting out of bed. "I feel great, and this is the first time I've been off steroids for an extended period," she says.
Patients and advocates say they're cautiously optimistic that one or more of the drugs will gain approval. "We have people diagnosed in the '60s who are still taking the same toxic drugs. This is not how most diseased states have progressed," says Sandra Raymond, president of the Lupus Foundation of America. "And finally we see a little light at the end of the tunnel."
Available treatments for lupus:
Two generic drugs approved to treat lupus are the mainstays of current therapy: One is prednisone, a steroid that reduces inflammation associated with lupus. Another is an anti-malarial drug, hydroxychloroquine.
Off-label treatments include methotrexate, originally a cancer treatment; transplant drugs CellCept and azathriopine; and the non- Hodgkin's lymphoma and rheumatoid arthritis treatment Rituxan.