Prescribing barriers

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.

Next: What derms need to know

What dermatologists need to know

Brodalumab labeling includes a boxed warning. While many of the tumor necrosis factor (TNF) antagonists have boxed warnings related to infection risk, brodalumab is the only biologic to have a boxed warning for depression and suicidality, Dr. Leonardi says.

Some of the highlights of the REMS program, according to Dr. Leonardi, are:

Prescribers must be certified by the program. What that means, specifically, is not yet known. According to Dr. Leonardi, it implies that dermatologists and others might have to pass a training course before becoming certified.

“And then you’ll be put into some database as a certified person who can prescribe the drug. That also means there will be some folks who are not allowed to prescribe it,” he says.

Patients must be counseled. “This is a challenge for dermatology, because we’ve never been involved in counseling our patients about depression, thoughts of suicide, what to do about harmful thoughts, whom to contact, etc. So, this is going to be new territory for us.”

New or worsening symptoms of depression or suicidality need to be referred to a mental health professional, as appropriate. That’s common sense, according to Dr. Leonardi.

“It’s just that, in dermatology, that doesn’t happen very often. So, just stipulating that will have to occur will put some dermatologists off,” he says.

Patients must sign a patient-prescriber agreement form. While that form wasn’t yet available when this story was written, Dr. Leonardi says it might highlight concerns about depression and suicide, and ask the patient to agree to accept the risks and notify the prescribing provider or emergency medical services if needed.

Pharmacies must be certified to dispense the drug to authorized patients. “It sounds like when the patient signs the agreement form, the data will flow upstream to some registry. That way the pharmacies can look that up and know that it’s okay to dispense to patients,” Dr. Leonardi says.

Challenges to dermatologists

All in all, this is a pretty bad program for prescribing brodalumab, according to Dr. Leonardi.

“If the boxed warning and the REMS program weren’t enough, brodalumab had run a trial in Crohn’s disease, and it made some of the patients worse. So, the FDA made it part of the label by stating that patients with Crohn’s disease should not use Siliq,” he says.

The question is whether dermatologists will even attempt to meet the requirements of the program to prescribe the drug. Dr. Leonardi says it’s highly unlikely that dermatologists will be prescribing this drug in any quantity.

“Who needs this drug? Dermatologists like me, believe it or not. I need it because … I literally have patients who have failed everything. That’s where this drug might come in. But using this drug in a casual way, as a first-, second- or even third-line drug, I’m not going to be doing that in my office,” he says.

Dr. Leonardi says he disagrees with those who claim brodalumab has unsurpassed efficacy in treating psoriasis.

“To be quite frank, that’s just not true. Right now, the current record holder is Taltz. Siliq and Taltz are very close, but I wouldn’t characterize one as being wildly better than the other,” he says. “There’s no question that brodalumab is a potent drug, it’s just that there are other choices that don’t involve this label and the REMS program.” ƒ

Disclosures: Dr. Leonardi has ties with Abbvie, Amgen, Celgene, Coherus, Dermira, Eli Lilly, Galderma, Glaxo Smith Kline, Janssen, Leo, Merck, Merck-Serono, Novartis, Pfizer, Sandoz, and Vitae. He is also a phototherapy provider and has an infusion center.