Mark Lebwohl, MD
The results of a multicenter clinical trial led by Mount Sinai Health System researchers and published in The New England Journal of Medicine on October 1, 2015, demonstrate that brodalumab, an experimental biologic treatment for plaque psoriasis, achieved 100 percent reduction in psoriasis symptoms in twice as many patients as a second, commonly used treatment.
“When it comes to complete skin clearing, our results are dramatically better than any previously published,” says lead study author Mark Lebwohl, MD, Sol and Clara Kest Professor and Chair of the Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai.
Plaque psoriasis is a non-contagious chronic disease in which the immune system causes skin cells to grow at an accelerated rate. Instead of being shed, skin cells pile up, causing painful scaly patches that can crack and bleed on the scalp, knees, elbows, and lower back. The lifelong disease affects 2 percent to 3 percent of the global population and can have a significant negative impact on quality of life.
The research team included, from left: Giselle K. Singer, Clinical Trials Manager; Fellows Peter Hashim, MD, Anjali Shroff, MD, and John Nia, MD; and Vicky Wong, Research Program Coordinator.
The study drug, brodalumab, is a monoclonal antibody, akin to the proteins built by the human immune system to recognize and block specific target molecules. Brodalumab was designed to block the function of the immune-signaling protein interleukin 17 (IL-17). If not blocked, IL-17 docks into specially shaped proteins, IL-17 receptors, to pass on signals that contribute to psoriatic inflammation.
“Studies have demonstrated that brodalumab binds to the IL-17 receptor, thus preventing IL-17 from doing so, to counter inflammatory diseases,” says Dr. Lebwohl. “Our results confirm that targeting the IL-17 receptor is highly effective in treating moderate-to- severe plaque psoriasis. Treatment was so effective that many patients did not have a dot of psoriasis left on their bodies.”
The main measure of treatment success is the degree of reduction in the Psoriasis Area Severity Index (PASI), which scores psoriatic plaque redness, scaling, and thickness of skin lesions, and the extent of the body involved. Until now, the goal was a 75 percent reduction in the PASI score, which is called PASI 75. A 100 percent reduction is known as PASI 100.
In one study, after 12 weeks, 44 percent of randomly selected patients receiving a 210-mg injection of brodalumab every other week achieved PASI 100, compared with 22 percent of patients treated with a leading psoriasis therapy. In the second study, 37 percent of patients randomized to receive the same dosage of brodalumab achieved PASI 100, compared with 19 percent of patients treated with the comparator drug. Also, with brodalumab, 86 percent of patients achieved PASI 75.
According to Dr. Lebwohl, brodalumab is the only IL-17 receptor antagonist in clinical development. The Phase 3 clinical trial—the final phase needed before the U.S. Food and Drug Administration considers an application for approval—was funded by drugmakers Amgen and AstraZeneca.