Scientists developing drugs to treat lupus face a daunting set of challenges. The disease, which affects 1.5 million Americans, results when the immune system mistakenly recognizes healthy tissues as dangerous and attacks them, touching off a range of responses. Some patients get arthritis and rashes, others develop heart disease, and some suffer kidney damage that can endanger their lives. And it still isn’t clear what causes all these symptoms.
Now two companies are working together to attack the disease with an experimental drug that tricks the immune system into behaving more normally. Results from phase II trials of the drug, called Lupuzor, showed a 53% improvement in symptoms among patients on the drug compared to a 36% improvement in those on placebo. That was enough to generate a tremendous amount of excitement leading up to the 9th International Congress on Systemic Lupus Erythematosus in Vancouver, British Columbia, which begins June 24. Lupuzor’s developers–ImmuPharma of London, U.K., and Cephalon of Frazer, PA–plan to release more detailed data from the trial during the conference.
Many drugs commonly used to treat autoimmune diseases, such as chemotherapy drugs, are known as immunosuppressants because they effectively shut down the entire immune system. Lupuzor, by contrast, is an immunomodulator–a drug that targets the specific immune cells involved in the disease. “In trials to date, we haven’t seen suppression,” says Peter Brown, vice president of clinical pharmacology and experimental medicine at Cephalon. That’s important because disabling the immune system entirely can cause unwanted side effects, such as dangerous infections.
Lupuzor targets T and B cells. In lupus, these immune cells malfunction, generating antibodies against proteins that healthy immune systems would normally ignore. Scientists at France’s National Center for Scientific Research split those proteins into smaller fragments and tested whether they might reverse the wayward immune response. One peptide was particularly effective in vitro, and in mouse models of lupus it significantly extended life. ImmuPharma, founded in 1999, led the early studies; Cephalon licensed Lupuzor in 2009 and is now in the early stages of planning a phase III trial.
The Vancouver conference should give physicians and scientists a more complete picture of how Lupuzor stacks up to other lupus drugs in development. Lupus experts have been paying particularly close attention to Human Genome Sciences’ Benlysta, a monoclonal antibody that targets B cells. The company is currently in phase III testing and is expected to release further details about its phase III results at the conference. So far, results have been impressive, with patients reporting significant reductions of “flares,” or bouts of debilitating symptoms.
No new drugs to treat lupus have been approved in over 50 years. Physicians currently have precious few choices for lupus treatment: chemotherapy, steroids that can control inflammation, and a malaria drug that works in some patients. But the side effects of harsher treatments can be so severe that “as many patients die from that as those who die from lupus,” says Tammy Utset, associate professor at the University of Chicago Medical Center who was also an investigator in the Benlysta trials.
Much of the challenge in developing lupus drugs stems from the variability of the disease. Some patients suffer flares frequently, for example, while others might get them only once a year. And the symptoms can strike many different organs. That makes measuring the response to an experimental drug difficult, says Sandra Raymond , CEO of the Lupus Foundation of America. To standardize these measurements, Human Genome Sciences worked closely with the U.S. Food and Drug Administration to develop a composite index that measures response to Benlysta according to several different parameters, including the number of both severe and moderate flares. The index also includes global assessments by treating physicians of whether or not the patients are getting worse. “What that’s done is carved a pathway for other companies, because they’ve put together an index that really gets at how the patient is feeling,” Raymond says.
Cephalon has yet to announce the timing of its phase III program or details about how it will measure patient response to Lupuzor in those trials. Still, the fact that there are any products at all in late-stage testing is a welcome relief to physicians like Kyriakos Kirou, a rheumatologist at the Mary Kirkland Center for Lupus Care at Hospital for Special Surgery in New York. “The drugs we have now are nonspecific and not very potent,” Kirou says. “We need to strike the right balance in controlling the immune system, and hopefully these new medicines will do a better job of that. It’s a very exciting time in lupus.”