Novartis has nnounced the results from the head-to-head Phase III FIXTURE study showing secukinumab (AIN457), an interleukin-17A (IL-17A) inhibitor, showed superior efficacy to etanercept in moderate-to-severe plaque psoriasis1. Etanercept is a NICE-approved anti-tumour necrosis factor (anti-TNF) therapy, used to treat moderate-to-severe plaque psoriasis2. These significant results are being presented today at the 22nd Congress of the European Association of Dermatology and Venereology (EADV) in Istanbul, Turkey1. Secukinumab is the first psoriasis treatment that selectively targets IL-17A to present Phase III results.
The pivotal FIXTURE study met all primary and pre-specified key secondary endpoints1. Both doses of secukinumab showed improved efficacy compared to etanercept throughout the 52 week study1.
“Psoriasis profoundly affects people’s lives both physically and psychologically and moderate-severe disease can be difficult to treat. These new data suggest that with secukinumab we may have the potential to help patients achieve clear skin, which is the ultimate treatment goal,” said Professor Chris Griffiths, Foundation Professor of Dermatology, The University of Manchester.
FIXTURE compared two doses of secukinumab (300 mg and 150 mg) with etanercept 50 mg and placebo1. The co-primary endpoints were assessed at Week 12 and compared secukinumab efficacy versus placebo and etanercept according to the Psoriasis Area and Severity Index 75 (PASI 75) and the Investigator’s Global Assessment (IGA mod 2011)1. Secukinumab 300 mg and 150 mg significantly increased PASI 75 rates versus placebo p<0.0001 (77.1% and 67.0% of subjects achieved a PASI 75 response rate respectively versus 44.0% with etanercept and 4.9% with placebo) at week 121. A significantly higher percentage of patients receiving secukinumab 300 mg and 150 mg also achieved a IGA 0/1 response rate (62.5% p<0.0001 ,and 51.1% p<0.0001 respectively) versus placebo, compared to 27.2% etanercept patients1.
Secondary endpoints assessed the efficacy of secukinumab versus placebo and etanercept over time and up to 52 weeks. It also assessed the safety and tolerability of secukinumab over 52 weeks. Secukinumab 150 mg and 300 mg sustained higher response rates over 52 weeks versus etanercept1. Secukinumab was also shown to clear skin more rapidly, with patients receiving secukinumab 300 mg achieving on average ~50% reduction in their PASI score after three weeks treatment, versus eight weeks with etanercept1.
Significantly more secukinumab patients experienced almost clear skin (described as PASI90) and completely clear skin (PASI100) compared to etanercept1, which are higher standards of skin clearance than the standard efficacy measure (PASI 75) used in most psoriasis clinical studies and in the NICE clinical guideline for psoriasis2.
The FIXTURE study showed that 54% of secukinumab 300 mg patients achieved at least a 90% reduction in skin redness, thickness and scaling (PASI 90)1 as early as Week 12, compared to 21% of etanercept patients (p<0.0001), additionally at week 16, 72% of secukinumab 300 mg patients achieved this higher standard of efficacy (PASI 90)1. Secukinumab 300 mg patients were also significantly more likely to experience completely clear skin compared to those taking etanercept in the study, as measured by PASI 100 at Week 16 (36.8% versus 7.4%)1.
Secukinumab efficacy was sustained over the full one year duration of the study. In FIXTURE, nearly twice as many patients treated with secukinumab 300 mg had a PASI 90 response at Week 52 compared to etanercept (65% vs. 33.4%)1.
There were no major safety signals identified in FIXTURE1. In FIXTURE, the incidence of adverse events (AEs) was similar between both secukinumab treatment arms (300 mg and 150 mg), and was comparable to etanercept1. The most common exposure adjusted AEs in any treatment group (including placebo) throughout the 52 week treatment period were nasopharyngitis and headache (occurring in between 12-36% of patients in all groups)1. At the same time point, non-fatal serious AEs (SAEs) were experienced by 5.8% of secukinumab 300 mg, 5.1% of secukinumab 150 mg and 6.2% of etanercept and 2.1% of placebo patients1. There were no deaths reported during the study1.
Secukinumab is an investigational medicine and the first psoriasis treatment that selectively targets IL-17A to present Phase III results. IL-17A is a central cytokine (messenger protein) involved in the development of psoriasis3. In psoriatic lesions there is increased expression of IL-17A3.
Psoriasis is a chronic inflammatory condition which is estimated to affect between 2% and 3% of the UK population4 – up to 1.8 million people5.
Secukinumab is not licensed for treatment in the UK.
Regulatory submissions for secukinumab in moderate to severe plaque psoriasis are on track for the second half of 2013.