FDA Approves Label Update for Secukinumab in Ankylosing Spondylitis

The U.S. Food and Drug Administration has approved a label update for secukinumab (Cosentyx, Novartis) to include the option for up-titration to a 300 mg dose for adults with active ankylosing spondylitis.

“This approval gives clinicians added flexibility to ensure patients are able to achieve the best response to treatment and experience full relief from the signs and symptoms of ankylosing spondylitis,” said Todd Fox, Global Head of Medical Affairs Immunology, Hepatology and Dermatology at Novartis.

Secukinumab, an anti-interleukin-17A monoclonal antibody, is approved for use in adults with moderate to severe psoriasis, active psoriatic arthritis and ankylosing spondylitis. Secukinumab was shown to improve the signs and symptoms of ankylosing spondylitis in the MEASURE 1 and MEASURE 2 trials.

The FDA approval of the label update was backed by data from the MEASURE 3 trial, a three-year study that assessed the efficacy and safety of secukinumab 300 mg and 150 mg subcutaneous maintenance dosing, following an intravenous loading regimen, versus placebo in 226 patients with ankylosing spondylitis.

“MEASURE 3 is the first study to assess the efficacy and safety of a 300 mg dose of secukinumab in ankylosing spondylitis,” wrote the authors, led by Karel Pavelka, M.D., Ph.D., of Charles University in Prague, Czech Republic.

The primary endpoint was the Assessment of SpondyloArthritis international Society criteria for 20 percent improvement (ASAS20) response rate at week 16 in the 300 mg or 150 mg groups versus placebo. Other endpoints assessed through week 52 included improvements in ASAS40, ASAS 5/6, Bath Ankylosing Spondylitis Disease Activity Index, ASAS partial remission responses, and change from baseline in high-sensitivity C-reactive protein levels.

The ASAS20 response rate was significantly greater at week 16 in the 300 mg (60.5 percent; P < 0.01) and 150 mg (58.1 percent; P < 0.05) groups versus placebo (36.8 percent). All secondary endpoints were met at week 16, except ASAS partial remission in the 150 mg group. Additionally, improvements achieved with secukinumab in all clinical endpoints at week 16 were sustained at week 52.

Long term data showed that the response rate was greater in the 300 mg dose group, particularly among patients with previous anti-tumor necrosis factor exposure, compared with the recommended 150 mg dose. By week 52, ASAS40 was met by 53.9 percent of patients assigned to secukinumab 300 mg compared with 40.5 percent of those assigned to secukinumab 150 mg, while ASAS partial remission 22.4 percent and 16.2 percent, respectively.

“The safety profile of secukinumab in this study was consistent with that observed in previous trials,” the authors wrote.

During the placebo-controlled period, infections, including candidiasis, were more common with secukinumab than with placebo. During the entire treatment period, pooled incidence rates of Candida infections and grade 3-4 neutropenia were 1.8 percent for both of these adverse events in secukinumab-treated patients.

REFERENCE

Novartis’ press release:  Novartis Cosentyx builds on its axSpA leadership with US label update for dosing flexibility in ankylosing spondylitis

Prescribing information for secukinumab

Karel Pavelka, Alan Kivitz, Eva Dokoupilova, et al. “Efficacy, safety, and tolerability of secukinumab in patients with active ankylosing spondylitis: a randomized, double-blind phase 3 study, MEASURE 3.”Arthritis Research & Therapy. December 22, 2017. https://doi.org/10.1186/s13075-017-1490-y