In February, the FDA approved brodalumab (Siliq/Valeant Pharmaceuticals) for adults with moderate-to-severe plaque psoriasis. The injectable biologic shines for its impact on the disease. In one phase 3 study published in 2015 in the New England Journal of Medicine, researchers reported that 44% of psoriasis patients taking 210 mg of brodalumab every two weeks had a complete response, or Psoriasis Area and Severity Index (PASI) 100, at week 12, and 86% achieved PASI 75.
Dermatologists who plan to prescribe brodalumab may face a rough road. Concerns about increased risks of suicidal ideation and behavior in phase 3 studies were so great that the FDA approved brodalumab with a boxed warning and instituted a Risk Evaluation and Mitigation Strategy (REMS) program that raises barriers to prescribing the drug.
Brodalumab, which is among three approved biologics for psoriasis that target interleukin (IL)-17, is slightly different from secukinumab (Cosentyx, Novartis) and ixekizumab (Taltz, Eli Lilly), which bind to IL-17a. Brodalumab blocks the IL-17a receptor, explains Craig L. Leonardi, M.D., adjunct professor of dermatology, Saint Louis University, and medical director of Central Dermatology, St. Louis, Mo.
Dr. Leonardi, who addressed the potential impact of the REMs program for dermatologists in a talk about new and emerging psoriasis treatments at the March 2017 annual Maui Derm meeting, says six suicides have occurred in research trials for brodalumab.
“Four of them occurred in psoriasis patients; two occurred in psoriatic arthritis trials. The FDA has characterized this as a strong signal for suicidal ideation and completed suicide — events that have not been observed to the same degree in other systemic psoriasis drug development programs,” Dr. Leonardi says.
But there’s more to this story.
“The other side of the argument,” according to Dr. Leonardi, “is when you look at the number of events, it is not statistically significant. In a strict accounting sense, it’s not known if these events are related. But what causes everybody to stop short is the serious nature of the event.”
As it usually does with new drugs or new mechanisms of action, the FDA convened a Dermatology, Ophthalmology, Drug Advisory Committee (DODAC) hearing. During the July 19, 2016 DODAC hearing on brodalumab, all 18 voting committee members recommended approval of the drug. Fourteen of the 18, however, voted for implementation of a REMS program, according to Dr. Leonardi.