NEW YORK, NY—The lupus therapeutic landscape is changing slowly but dramatically because of the advent of molecular tools (such as  the sequencing of the human genome) and the development of targeted treatments. Lupus experts speaking at a teleconference on September 25 at the Lupus Research Institute's (LRI) 2007 Forum for Discovery Scientific Conference said that moving these therapeutic advances into the clinic will require enrolling many more lupus patients into clinical trials.¹

"Overall, we have achieved a lot of new thinking about this disease. The molecular tools and models are there to make advances, and  I think we are going in the right direction," said LRI president Margaret Dowd.

Seeking lupus clinical trial participants

The 40-year drought since the most recent lupus drug approval looks likely to end soon.  The drug development pipeline is full, the experts agreed.

The current challenge, therefore, is how to persuade lupus patients to participate in clinical trials—a whole new world for them.

"This is a community that  has never known a new drug," said Dowd. Unlike cancer patients, who are well versed in clinical trials, lupus patients are often uninformed about or mystified by  this process.

Bevra Hahn, MD, chief of rheumatology at the University of California at Los Angeles School of Medicine, agreed. "I currently have five active trials for novel treatment and am hoping that we will have 10," she said.  "There is a lot going on, but it's very difficult to get patients to volunteer."

"Patients need to sign up, and physicians have to encourage their lupus patients to do that," said panel moderator Lee S. Simon, MD, rheumatologist at Harvard Medical School, in Boston, Massachusetts. To that end, the LRI has started a website (www.lupustrials.org) to encourage participation.

Nail-biting race to the finish line for the next lupus drug

"It's a horse race," Robert S. Katz, MD, associate professor of medicine at Rush-Presbyterian-St. Luke's Medical Center, in Chicago, told CIAOMed. He said that  27 drug companies are now interested in lupus. "The new therapies are more targeted and are not just immune system tranquilizers." 

Leaders in the horse race include abatacept (Orencia®),  rituximab (Rituxan®), and belimumab (lymphoStat-B). "It's hard to know which will be approved first," Dr. Katz  said.

But the enthusiaism is about more than just medications, added Greg E. Lemke, PhD, a professor of molecular neurobiology  at the Salk Institute for Biologic Studies, in San Diego, California.

"One of the reasons that there is excitement in lupus and other complex diseases is because of the advent of a whole series of new molecular tools [including the] sequencing of the human genome." Dr. Lemke said. "We now have insight into the molecular causes of many complex diseases."

Knock-out mice lead the march from bench to bedside

Such tools have helped to unearth potential novel biomarkers including proinflammatory high density lipoprotein (HDL) as an indication for carotid artery plaque in women with lupus.
"We have found that half of women with lupus have proinflammatory HDL instead of normal HDL," said Dr. Hahn. By contrast, only 4% of lupus-free or healthy people have these abnormalities.

Moreover, "almost all people with lupus who had heart attack or stroke had abnormal HDL, and carotid ultrasound studies found that 90% of women with plaque have abnormal HDL," she says. "It looks more and more like proinflammatory HDL predisposes lupus patients to atherosclerosis."

Dr. Hahn's team also helped develop a mouse model with accelerated atherosclerosis, lupus, and proinflammatory HDL. The group is currently studying whether a combination of statins and oral cyclic peptides can prevent atherosclerosis in this mouse model.

"We should know the answer in the next 5 years," Dr. Hahn said.

 

Reference

1.  Breakfast Briefing With Experts on Lupus: Slew of Discoveries Brings Hope to Sufferers of Devastating Autoimmune Disease. 2007 Forum for Discovery LRI Scientific Conference; September  24-25, 2007; New York, NY.