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Secukinumab approved for psoriasis

March 5, 2015

Article

Secukinumab has received FDA approval as a new treatment option in psoriasis. A panel of experts tackles this drug’s uses, benefits, and drawbacks.

The FDA has given its thumbs up to what dermatologists say is an exciting treatment option in psoriasis: secukinumab (Cosentyx, Novartis).

Dermatologists and a rheumatologist gathered for the Psoriasis 2015 panel presentation during the January MauiDerm meeting in Maui, Hawaii. Among the topics of discussion: how this newly approved medication fits into the dermatologists’ ever-growing toolbox aimed at clearing skin disease and restoring quality of life.

Self-injectable biologic therapy

Secukinumab is a first-in-class, novel biologic therapy for moderate-to-severe psoriasis in adults. The FDA approved Secukinumab in January 2015. Patients self-inject this systemic medication once weekly for the first five injections and once monthly thereafter.

“It works by blocking [interleukin] IL-17. In this regard, it is a brand new mechanism of action that will be employed by follow-on drugs in the coming years,” said Bruce Strober, M.D., Ph.D., who led the panel discussion and is associate professor and vice chair at the University of Connecticut School of Medicine. “Based on clinical trials data, secukinumab, to date, offers the highest level of clinical response when compared to other FDA-approved self-injectable biologic therapies.”

Attention has shifted to targeting cytokines versus affecting T-cells directly. And the cytokine approach has been much more successful, according to Craig Leonardi, M.D., clinical professor of dermatology at St. Louis University, St. Louis, Mo., and a MauiDerm panel member.

Dr. Leonardi said that dermatologists can understand secukinumab’s mechanism of action by reading the results of two phase 3 trials published July 24 in the New England Journal of Medicine.[1] The paper includes data on the 150mg and 300mg doses of secukinumab compared to the 50mg dose of etanercept. Among the findings: secukinumab patients respond in approximately three weeks versus etanercept patients in approximately seven weeks, according to Dr. Leonardi.

“I generally see my [psoriasis] patients back at one month. With a drug like [secukinumab], you’re likely to understand at that visit whether the drug is going to achieve results you expect,” Dr. Leonardi said.

Researchers found the proportion of patients who met the criterion for PASI 75 at week 12 was higher with each secukinumab dose than with placebo or etanercept. In one study, the rates were 81.6% with 300mg of secukinumab, 71.6% with 150mg of secukinumab, and 4.5% with placebo.

The second study showed 77.1% with 300mg of secukinumab, 67.0% with 150mg of secukinumab, 44.0% with etanercept and 4.9% with placebo, according to the study’s abstract.

Researchers also found that the proportion of patients with a response of 0 or 1 (“clear or almost clear”) on the modified investigator's global assessment at week 12 was higher with each secukinumab dose than with placebo or etanercept. In the study comparing the two psoriasis drugs, rates were 62.5% with 300mg of secukinumab, 51.1% with 150mg of secukinumab, 27.2% with etanercept, and 2.8% with placebo. Infection rates were similar between secukinumab and etanercept, and higher than with placebo.

FDA’s interest

“When this drug had its day in front of the FDA… I must say it was a love fest,” Dr. Leonardi said.

Interestingly, the FDA’s analysis, which is done independently, looked at what percentage of patients would achieve clear or almost clear responses based on concentrations of the drug that are achieved after injection.

“This is the first time ever that I’ve seen the FDA, or anyone, predict a response based on serum concentration. It’s a more informed way of using the medicines we prescribe-especially the expensive ones,” Dr. Leonardi said.

“The FDA … suggested the heavy (high weighted) patients would be better served if they went with a 450mg dose-a dose that had never been tested,” he added. “Remarkably, the FDA … asked the company whether they’d consider doing a 450mg trial.”

Dr. Leonardi said that the drug’s labeling is interesting: It recommends 300mg, at baseline, weeks one, two, three, and four, then 300mg every four weeks.

“Then they make the comment that, for some patients, the 150mg dose may also be acceptable. This language implies flexibility in dose selection,” Dr. Leonardi said. “I think we should be able to use expensive resources in ways that are creative and best for our patients, our specialty, and society.”

NEXT: indication on horizon?

New indication on horizon?

Secukinumab is also being studied for psoriatic arthritis

Researchers at the American College of Rheumatology meeting in November 2014 in Boston presented the first phase 3 trial to evaluate highly selective IL-17A inhibition in patients with psoriatic arthritis. They concluded that secukinumab provides rapid, clinically significant, and sustained improvements in signs and symptoms, and also inhibits joint structural damage. The drug was well tolerated through 52 weeks, according to the abstract.[2]

Arthur Kavanaugh, M.D., among the panel members at MauiDerm and professor of medicine at University of California San Diego, said that, while the data on secukinumab looks good for psoriatic arthritis, TNF inhibitors are still the focal point for the treatment of moderate-to-severe psoriatic arthritis. Still, choosing a specific drug to treat psoriatic arthritis comes down to patient choice.

“I present data to them, and the patient picks,” Dr. Kavanaugh said. “No drug works 100% for every person. So much of what we do is still trying a drug and, if that isn’t the best fit, try another.”

As for dosing secukinumab, data from studies presented at the ACR’s meeting last year in Boston suggest that for some people with psoriatic arthritis, the 150mg secukinumab dose might be as effective as 300mg, according to Dr. Kavanaugh.

Choosing highly effective drugs

Dr. Leonardi presented data showing how many patients one has to treat with any one of the various psoriasis drugs to achieve a single patient who achieves a PASI 75 response. Etanercept is about 2.2 patients; infliximab about 1.4; and 1.6 patients for adalimumab and ustekinumab. For secukinumab, it’s 1.3, according to Dr. Leonardi.

“It’s quite remarkable. If you treated 13 patients with secukinumab, 10 would achieve a PASI 75,” he says.

One other question that doctors and patients have on their minds is whether treating psoriasis might actually lower cardiovascular disease risk. For the new drugs, it’s too early to tell, according to MauiDerm panel member Joel M. Gelfand, M.D., M.S.C.E., associate professor of dermatology and epidemiology at University of Pennsylvania Perelman School of Medicine in Philadelphia.

“Observational data from rheumatoid arthritis and psoriasis patients suggest that methotrexate and TNF inhibitors are associated with a decreased risk of cardiovascular events. Similar data are not yet available for ustekinumab or the newly approved apremilast and secukinumab,” Dr. Gelfand said.

References

[1] Langley RG, Elewski BE, Lebwohl M, et al. Secukinumab in plaque psoriasis--results of two phase 3 trials. N Engl J Med. 2014;371(4):326-38.

[2] Mease, Philip J., Et Al. "Secukinumab, A Human Anti–Interleukin-17A Monoclonal Antibody, Improves Active Psoriatic Arthritis and Inhibits Radiographic Progression: Efficacy and Safety Data from a Phase 3 Randomized, Multicenter, Double-Blind, Placebo-Controlled Study - ACR Abstracts." ACR Abstracts. ACR Annual Meeting, Boston, Mass., Abstract 953, Nov. 2014. Web. 23 Feb. 2015.