Boston, MA—Secukinumab, an interleukin (IL)-17A inhibitor, was found effective in pivotal phase 3 studies among patients with ankylosing spondylitis (AS) and psoriatic arthritis (PsA). The drug was recently approved by the US Food and Drug Administration, and with the new phase 3 data, approval is expected for AS and PsA in 2015.
Two groups of phase 3 studies presented at the American College of Rheumatology (ACR) 2014 Annual Meeting: MEASURE 1 and MEASURE 2 in patients with AS, and FUTURE 1 and FUTURE 2 in patients with PsA.
Two other IL-17A antibodies— brodalumab and ixekizumab—are under way and both have had positive results in phase 3 studies of PsA.
“Secukinumab is the first non-TNF [tumor necrosis factor] drug to demonstrate responses in AS, and responses were seen in both TNF-exposed and non-TNF-exposed patients,” said lead author of MEASURE 1, Dominique Baeten, MD, PhD, Professor of Clinical Immunology and Rheumatology at the Academic Medical Center, University of Amsterdam, the Netherlands. “We saw rapid and sustained relief in signs and symptoms of AS.”
MEASURE 1 and MEASURE 2 had similar designs and both studies compared subcutaneous 75 mg and 150 mg of secukinumab; the 150-mg dose was found to be the most effective.
The primary end point of MEASURE 1 (N = 482), which was a 20% improvement in signs and symptoms according to Assessment of SpondyloArthritis International Society criteria (ASAS20) was 60.8% for the 150-mg dose and 59.7% for the 75-mg dose, versus 28% for placebo at week 16 (P <.0001). ASAS40, which is a 40% improvement, was achieved in 41.6% and 33.1% of the treated groups versus 13.1%, respectively (P <.001). All secondary end points were met for both treatment arms versus placebo, including high-sensitivity C-reactive protein, Bath AS Disease Activity Index, quality of life as assessed by the 36-Item Short Form Health Survey and the AS Quality of Life, and Assess Spondyloarthritis partial remission.
After week 24, all of the patients were randomized to 1 of the 2 doses of secukinumab during an open-label phase. At week 52, responses were maintained in both treatment arms, both in anti–TNF-exposed and anti–TNF-naïve patients.
Secukinumab was well tolerated; a higher number of adverse events and serious adverse events were reported in the placebo group. No serious infections were reported, and immunogenicity was low.
MEASURE 2 results were similar for secukinumab in patients with AS.
FUTURE 1 and FUTURE 2 are the first phase 3 studies of a selective IL-17A inhibitor in PsA. FUTURE 1 compared 75 mg and 150 mg of secukinumab of with placebo, and FUTURE 2 compared 75 mg, 150 mg, and 300 mg with placebo.
Both studies met the primary end point of the ACR 20% (ACR20) improvement from baseline at week 24. In FUTURE 1, ACR20 was achieved in 50.5% and 50% of the 75-mg and 140- mg arms, respectively, versus 17.3% for placebo (P <.0001). In FUTURE 2, ACR20 was achieved in 29.3% for secukinumab 75 mg (P <.05); 51% and 54% for secukinumab 150 mg and 300 mg, respectively, versus 15.3% for placebo (P <.0001).
Secukinumab was well tolerated in both studies, with a similar adverse event profile as in the MEASURE 1 and MEASURE 2 studies.—PS