Secukinumab Takes Another Step Toward FDA Approval

The compound AIN457 (secukinumab) has been granted a unanimous vote of support for approval from the Dermatologic and Ophthalmic Drugs Advisory Committee to the Food and Drug Administration.

The compound AIN457, or secukinumab, has been granted a unanimous vote of support for approval from the Dermatologic and Ophthalmic Drugs Advisory Committee (DODAC) to the Food and Drug Administration (FDA).

Secukinumab is indicated for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy. The recommendation for approval from the DODAC is based on safety and efficacy outcomes observed in ten Phase II and III clinical studies of secukinumab that included nearly 4,000 patients with moderate-to-severe plaque psoriasis. The Phase III clinical program for secukinumab included four placebo-controlled pivotal studies that examined secukinumab in 300 mg and 150 mg doses.

In these studies, secukinumab met all primary and key secondary endpoints, including Psoriasis Area and Severity Index (PASI) 75 and 90 and Investigator's Global Assessment modified 2011 (IGA mod 2011) 0/1 responses. Significant skin clearance was observed at Week 12. In addition, a majority of patients treated with secukinumab who achieved PASI 75 response and IGA mod 2011 0/1 at Week 12 maintained the response at Week 52 with continued treatment.

Data on secukinumab that is currently available shows no major safety issues. The incidence of serious adverse events (SAEs) was low and comparable for both 300 and 150 mg doses of secukinumab and placebo (2.0% for both 300 mg and 150 mg vs. 1.7% for placebo) in the pooled analyses of the placebo-controlled period of the Phase III studies. Commonly reported adverse events (AEs) observed with secukinumab were nasopharyngitis, headache, diarrhea, pruritus, and upper respiratory infection.

In relation to psoriasis, Vas Narasimhan, global head of Development for Novartis Pharmaceuticals, the manufacturer of secukinumab, says, “There is a need for novel therapies, as not all treatments are appropriate or effective in every patient. Today's recommendation is based on the efficacy and safety data put forth in our robust clinical trial program and brings us one step closer to delivering an innovative, new treatment option for people suffering from moderate-to-severe psoriasis. We look forward to working with the FDA as it finalizes its review."

Novartis submitted a Biologics License Application (BLA) for secukinumab to the FDA in October 2013; the FDA action date is expected in early 2015. Submissions have also been made with regulatory authorities in the European Union (EU); a decision from the EU is anticipated in late 2014 or early 2015.

Phase III data on the use of secukinumab for psoriatic arthritis and ankylosing spondylitis are expected later this year, according to Novartis.

Secukinumab is a first-in-class human monoclonal antibody (mAb) and the first interluekin (IL) 17A (IL-17A) inhibitor to be reviewed by the FDA for moderate-to-severe plaque psoriasis. It has been shown to selectively bind to and neutralize IL-17A, inhibiting the release of pro-inflammatory cytokines, or messenger proteins. IL-17A is a key messenger protein involved in the development of plaque psoriasis that is found in high concentrations in psoriasis skin plaques.

IL-17A is among a number of interleukins that are being targeted for psoriasis therapy; another common IL is IL-23.