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Dr. Mark Lebwohl talks about the FDA’s approval of the anti-interleukin-17 receptor monoclonal antibody brodalumab (Siliq, Valeant Pharmaceuticals) for treatment of adults with moderate-to-severe plaque psoriasis.
The FDA has approved anti-interleukin-17 receptor monoclonal antibody brodalumab (Siliq, Valeant Pharmaceuticals) to treat adults with moderate-to-severe plaque psoriasis.
The injectable systemic therapy blocks the receptor for IL-17, so it has a mechanism of action similar to approved biologics secukinumab (Cosentyx, Novartis) and ixekizumab (Taltz, Eli Lilly), which block IL-17 itself, according to Mark Lebwohl, M.D., professor and chair of dermatology, Icahn School of Medicine at Mount Sinai, who was involved with the clinical trials that paved the way for brodalumab’s FDA approval.
Dr. LebwohlBrodalumab is as effective or more effective than any other FDA-approved drug to treat psoriasis, according to Dr. Lebwohl, who was lead author on the New England Journal of Medicinepaper examining phase 3 studies comparing brodalumab with ustekinumab (Stelara, Janssen), for psoriasis.1
“In its phase 2 data, it (brodalumab) was the most effective drug that we had ever seen. Nearly two-thirds of plaque psoriasis patients achieved (psoriasis area-and-severity index) PASI 100. That’s a number we’ve never seen-two-thirds of people not having a dot of psoriasis left,” Dr. Lebwohl says.
Phase 3 studies PASI 100 percentages were lower, but still unprecedented, according to Dr. Lebwohl.
Researchers reported in the NEJM that PASI 75 response rates at week 12 were 86% with the 210-mg brodalumab dose and 67% with 140-mg of the biologic, versus 6% in the placebo group. In two other studies, from 44 to 37% of psoriasis patients on 210 mg of brodalumab achieved PASI 100 at 12 weeks, versus 22 to 19% of patients on ustekinumab. The approved dose is 210 mg.
“The downside, which will appear in the label, is that there were a small number of suicides. In the psoriasis trials, there were four (suicides) out of 4,000 treated patients. In all the trials, there were six (suicides) out of 6,000 treated patients. Although it is not clear that the suicides had anything to do with the drug, that raised an alarm at the FDA, and they put it into the package insert,” Dr. Lebwohl says.
Concerns about suicide helped to make brodalumab’s road to approval a rocky one. In January 2016, the National Psoriasis Foundation published an article that Amgen, which along with AstraZeneca had been developing brodalumab, stopped developing the biologic because of suicidal thought and behavior concerns during clinical trials. AstraZeneca later auctioned off brodalumab to Valeant.
According to FDA, subjects in the trials were more likely to think about suicide or commit suicide if they had a history of suicidality or depression. But a causal association between treatment with brodalumab and increased suicidal ideation and behavior risks has not been established.
Dr. Lebwohl says he is familiar with each of the patients who committed suicide during the psoriasis trials and thinks it was more bad luck than a pattern in treated patients. But because of the black box warning, dermatologists and other prescribers need to counsel patients about the potential risk, he says.
“I, interestingly, have a patient who I have taken care of for many years and has failed every treatment out there. I actually hospitalized her in 2002 because I was worried she was going to commit suicide,” Dr. Lebwohl says. “This is the first drug after all those years that was able to clear her completely. Since the trials ended, she has been on the other IL-17 drugs with either a minor or moderate response. So, she’s waiting to get back on this when it comes out.”
Siliq should be available to patients in the second quarter of 2017, he says.
Disclosure: Dr. Lebwohl has been an investigator for the makers of brodalumab.
1 Lebwohl M, Strober B, Menter Alan, Gordon K, Weglowska J, Puig L, et al. Phase 3 Studies Comparing Brodalumab with Ustekinumab in Psoriasis. N Engl J Med 2015; 373:1318-1328