(ACR2014) With FDA approval of the new IL-17A inhibitor expected soon, results of the latest clinical trials presented here show the expected benefits of a first-of-its-kind treatment for axial spondylitis, psoriatic arthritis, and psoriasis.
With FDA approval of secukinumab expected soon, results of the latest clinical trials promise a first-of-its-kind treatment for axial spondylitis (AS), psoriatic arthritis (PsA), and psoriasis.
Clinical trials reported here at the annual meeting of the American College of Rheumatology (ACR) show that the interleukin-17A (IL-17A) inhibitor significantly reduces radiographic progression and joint damage in AS and PsA, while improving physical function and quality of life.
“The first approval of secukinumab is likely to be in psoriasis, because those studies have been going on longer. But the FDA now has all the data from two substantial phase III trials, so approvals for AS and PsA are likely to follow,” remarks Philip J. Mease MD, director of rheumatology research at the Swedish Medical Center in Seattle and a clinical professor of medicine at the University of Washington. Mease is a key investigator in the studies.
“The application will be for subcutaneous administration. So the expected approach in treating AS and PsA will be either with 150 mg or the 300 mg dose, if both are approved,” Mease told Rheumatology Network. “If you look at the magnitude of skin response and the quality of responses among patients who have previously been exposed to anti-TNF agents, the 300 mg dose works better than 150 mg. That’s why we would like to have it available in both doses to give us some flexibility.”
Secukinumab selectively binds to and neutralizes IL-17A, a proinflammatory cytokine that plays a key role in the pathogenesis of AS, PsA, and plaque psoriasis. It has been studied in more than 10 clinical trials among 40,000 psoriasis patients, as well as in AS and PsA.
In the 24-week FREEDOM 2 trial, the 300 mg dose of secukinumab proved effective in active PsA in both TNF-exposed and TNF-naÃ¯ve patients, reports Iain B. McInnes PhD, the trial leader and Muirhead Chair of Medicine at the University of Glasgow, UK.
FREEDOM 2 is a phase 3, randomized, placebo-controlled, multi-center trial conducted among 379 patients with active PsA selected to receive one of three doses of subcutaneous secukinumab (300 mg, 150 mg, or 75 mg). The two higher doses provided clinically significant improvements in ACR20 responses at 4 months in more than half of patients on those doses (54% for 300 mg, 51% for 150 mg). Clinically significant responses were seen regardless of whether or not patients had previously taken TNFi drugs.1
Other major clinical trials reported at ACR also show impressive benefits:
• MEASURE 2: A 52-week, phase 3, randomized controlled trial conducted among 371 patients in the Netherlands found that secukinumab provides swift and substantial improvement in signs and symptoms of active AS, starting as soon as one week and lasting through 52 weeks.2
The trial employed two subQ doses of secukinumab, 75 mg and 150, with the higher dose proving more effective, reports lead investigator Dominique l. Baeten, MD, of the University of Amsterdam. “There were also significant and rapid responses both in signs and symptoms and radiographic progression,” Baeten told a press conference.
• FUTURE 1: A one-year multicenter phase III trial among 606 patients with severe PsA (which used both intravenous and subQ secukinumab) found that the IL-17 blocker significantly inhibited radiographic progression regardless of TNF status or concomitant MTX administration after 52 weeks.3
• Another phase III randomized trial, this one among 371 AS patients (also using IV and subQ doses), found that secukinumab produced rapid and sustained improvements in patient reported outcomes including fatigue, quality of life and work productivity.4
All of the trials report a favorable risk-benefit safety profile, with the main adverse events including Candida infections and neutropenia.
On October 20th, the FDA’s Dermatologic and Ophthalmic Drugs Advisory committee voted unanimously to recommend approval of secukinumab for the treatment of moderate to severe plaque psoriasis in adults. Formal approval is expected before the end of the year.
The FDA panel also recommends that a 450-mg dose of secukinumab, which was not formally studied in the clinical trials, be evaluated in postmarketing studies.
Other IL-17 inhibitors currently in phase III trials show promise in PsA, including ustekinumab (Stelara), brodalumab, and ixekizumab, an experimental IL-17A-blocker.6
1-ACR Late-breaking abstract L1: McInnes IB, Mease PJ, Kirkham B, et al., Secukinumab, a human Anti- Interleukin 17A, Monoclonal antibody, Improves Active Psoriatic Arthritis: 24-Week Efficacy and Safety Data from a Phase 3, Randomized, Multicenter, Double-Blind, Placebo-Controlled Study Using Subcutaneous Dosing. Presented Tuesday, November 18, 4:30 PM. ACR 2014 Annual Meeting, Boston, MA.
2- Baeten DL, Braun J, Baraliakios, et al., Secukinumab, a Monoclonal Antibody to Interleukin-17A, Significantly Improves Signs and Symptoms of Active Ankylosing Spondylitis: Results of a 52-Week Phase 3 Randomized Placebo-Controlled Trial with Intravenous Loading and Subcutaneous Maintenance Dosing. Arthritis & Rheumatism (2014) 66(1) Supplement. ACR Abstract #819.
3-Mease PJ, McInnes IB, Kirkham B, et al. Secukinumab, a Human Anti–Interleukin-17A Monoclonal Antibody, Improves Active Psoriatic Arthritis and Inhibits Radiographic Progression: Efficacy and Safety Data from a Phase 3 Randomized, Multicenter, Double-Blind, Placebo-Controlled Study. Arthritis & Rheumatism (2014) 66(1) Supplement. ACR Abstract #953
4-Deodhar AA, Baeten DL, Brun J, et al., Secukinumab, a Monoclonal Antibody to Interleukin-17A, Significantly Improves Physical Function and Quality of Life in Subjects with Active Ankylosing Spondylitis: Results of a Phase 3 Randomized, Placebo-Controlled Trial with Intravenous Loading and Subcutaneous Maintenance Dosing. Arthritis & Rheumatism (2014) 66(1) Supplement. ACR Abstract #538
6-http://www.rheumatologynetwork.com/psoriatic-arthritis/despite-new-drugs-psa-treatment-options-still-fall-short#sthash.LNyOZtr7.dpuf and http://www.rheumatologynetwork.com/psoriatic-arthritis/il-17-superfamily-what-future-psa