You are here
FDA Advisors Say Benefits of Psoriasis Drug Secukinumab Outweigh Risks
According to a Reuters report, the FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee has ruled that the clinical benefits of the anti-inflammatory medication secukinmuab (Novartis) outweigh the risks involved in using it to treat plaque psoriasis.
While the FDA is not obligated to accept the recommendations of its advisory panels, it usually does so.
The ruling was announced a few days before a panel of outside advisors is scheduled to meet to discuss the drug.
Secukinumab is an injectable human immunoglobulin G1 (IgG1) monoclonal antibody that binds to the pro-inflammatory cytokine interleukin-17A (IL-17A) and inhibits its interaction with the IL-17 receptor. IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses and plays a role in the pathogenesis of plaque psoriasis.
The serum levels of total IL-17A (free and secukinumab-bound IL-17A) increased following secukinumab treatment in subjects with psoriasis. One hypothesis to explain the increased IL-17A concentrations was that the clearance of IL-17A-secukinumab complex was slower than that of free IL-17A.
FDA approval is being sought for the use of subcutaneous secukinumab in the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy.
The proposed indication was supported by 52-week safety and efficacy data from two pivotal phase III trials (studies 2302 and 2303) and by 12-week safety and efficacy data from two additional phase III studies. Six phase II/III trials have been conducted in subjects with moderate-to-severe plaque psoriasis.
Secukinumab (300 mg and 150 mg) was superior to placebo in the treatment of moderate-to-severe plaque psoriasis in studies 2302 and 2303. An Investigator’s Global Assessment (IGA) score of “clear” or “nearly clear” was achieved by 65% and 51% of subjects treated with secukinumab 300 mg and 150 mg, respectively, compared with 2% for the placebo group in study 2302. Similarly, An IGA score of “clear” or “nearly clear” was observed in 62% and 51% of subjects treated with secukinumab 300 mg and 150 mg, respectively, compared with 3% for the placebo group in study 2303.
Observations in humans with genetic defects affecting the Th17 pathway and in individuals who have genetic defects in IL-17 signaling suggest that blockade of IL-17 increases the risk for fungal infections, particularly mucocutaneous candidiasis, as well as staphylococcal skin infections.
In the secukinumab development program, common infections, such as nasopharyngitis and upper respiratory tract infection, were reported more frequently in the two secukinumab dose groups compared with placebo. Serious infections were infrequent.
A higher rate of mucocutaneous candida infections with secukinumab, particularly the higher dose, was observed consistently at both 12 weeks and throughout the entire treatment periods.
There was no evidence that secukinumab confered an increased risk for malignancy.
Sources: Reuters; October 16, 2014; and FDA Briefing Document; October 2014.