New Biologic for Psoriasis Gets FDA Panel Nod of Approval

Larry Hand

October 20, 2014

A US Food and Drug Administration (FDA) advisory committee voted unanimously today to recommend approval of a first-in-class drug for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.

The Dermatologic and Ophthalmic Drugs Advisory Committee voted 7 to 0 to recommend approval of secukinumab (Cosentyx, Novartis Pharmaceuticals). Secukinumab is a fully human monoclonal antibody that inhibits the proinflammatory cytokine interleukin-17A.

Other biologic drugs have been approved and are in use for treating plaque psoriasis, but they act on different mechanisms.

Psoriasis affects 2% to 3% of the population, but patients with moderate-to-severe disease make up 15% to 25% of those patients.

Novartis submitted results of four phase 2 studies involving 660 patients and four phase 3 studies involving more than 5000 patients in support of its FDA application. After the phase 2 studies established dose and regimen avenues to pursue, researchers studied two dose levels — 150 and 300 mg — in phase 3 studies, against placebo in 3 studies, and against comparator etanercept (Enbrel, Amgen) in one study.

Secukinumab is injected subcutaneously in one of three forms: a lyophilized formulation for reconstitution and a liquid formulation administered by either a prefilled syringe or autoinjector pen. Novartis tested all formulations.

The phase 3 studies "consistently demonstrated that secukinumab provided clinically meaningful, significant improvement," Novartis told the committee members in a background document.

"Unprecedented Efficacy"

"This drug confers unprecedented efficacy" for subcutaneously injected drugs for treated plaque psoriasis, Bruce E. Strober, MD, PhD, vice chair of dermatology at the University of Connecticut, Storrs, and a clinical investigator for the drug, told panel members.

The safety profile of secukinumab is similar to that of other drugs with any identified risks commonly manageable clinically, and secukinumab offers a greater chance of "alleviating and incapacitating" the disease, he said.

The 300-mg dose showed significantly better improvement than the 150-mg dose, according to Novartis.

Although FDA officials generally agreed with the efficacy results from Novartis, they brought up some questions about the dosing, which generated considerable discussion by panel members.

FDA officials said an exploratory subgroup analysis showed that a higher rate of mucocutaneous Candida infections occurred particularly with the 300-mg dose, showing that both an exposure-response and a dose-response relationship existed for Candida infections, although the rate of infections overall was infrequent. The relatively short-term data for a disease that lasts years presents an unclear picture of the potential impact of immunomodulating drugs on autoimmunity diseases, including some cancers.

Even Higher Dose?

But FDA officials also told panel members that efficacy for secukinumab "increases as concentration increases." They asked for advice from the panel on whether a postmarketing study should be done on a 450-mg dose.

In summary, the higher dose could offer benefit to heavier-weight patients (≥ 90 kg) who are nonresponders or slow responders to the 300-mg dose, while a 150-mg dose might be enough for patients who weigh less than 90 kg, FDA officials offered up. The 150-mg dose may be safer, but the 300-mg dose has better overall efficacy, in other words.

Jee Eun Lee, PhD, a pharmacometrics reviewer for the FDA told panel members that the risk-benefit ratio for secukinumab for patients who weigh less than 90 kg and take 300 mg is 15% risk of infection and 64% risk of benefit.

Novartis officials argued heavily for the 300-mg dose because, they said, insurance companies would refuse to pay for it if the smaller dose were recommended in labels. They offered information showing that the safety profiles were similar during testing for people who weigh 70, 90, or > 90 kg.

Committee Chair Lynn A. Drake, MD, a dermatologist at Massachusetts General Hospital and a lecturer at Harvard Medical School, Boston, said risk-benefit ratios are more than just numbers, however, and asked for examples of how serious this disease is and how it can affect patients.

Novartis officials offered examples of patients getting denied access to swimming pools, hair salons, and other places because people don't understand the disease, as well as excessive absenteeism and lack of full capacity in jobs.

Real-Life Experience

One clinical trial patient described during the public hearing part of today's meeting exactly what it meant to him.

Ethon Woods, 38, of St. Louis, Missouri, said he had psoriasis on 30% of his body at baseline during the study. Taking secukinumab led to a reduction to 8.4% after two months and to 0% after 16 weeks, and he said he has been completely clear for three years.

He told panel members that the treatment gave him more confidence to perform his job as a casino blackjack dealer and he now goes to the swimming pool.

FDA staff only asked for advice on the dose issue, and the panel did not vote on it. Chair Dr Drake summed it up: "We think it is an effective drug and would like to see both available, although it looks like the 300 mg may be best. Safety does not seem to be a huge problem at this point."

She added that secukinumab "is unique and its new" and it doesn't need to be overly compared with other drugs.

In general, the panel members felt that the 450-mg does should be studied in a randomized trial postapproval of the 300-mg dose.

No panel members reported any relevant financial relationships.

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