Novartis announced results from the pivotal phase III FEATURE and JUNCTURE studies showing secukinumab (AIN457), an interleukin-17A (IL-17A) inhibitor, demonstrated consistent high efficacy when administered with a convenient pre-filled syringe (PFS) or autoinjector/pen (AI).These results, along with patient-reported outcomes showing high patient satisfaction with PFS and AI, were presented for the first time at the 72nd Annual Meeting of the American Academy of Dermatology (AAD) in Denver, USA.
FEATURE and JUNCTURE are the first phase III studies to evaluate secukinumab in clearing patients' skin with the PFS and AI administration. Both methods allow secukinumab self-administration anywhere (including the workplace or home) versus healthcare professional administration, if allowed by local regulations. This is important because many psoriasis patients prioritise easy self-administration at a location of their choice.
"It is important that people living with psoriasis, a chronic skin disease, have highly effective and safe treatments they can conveniently self-administer," said Tim Wright, Global Head of Development for Novartis Pharmaceuticals. "These exciting results from our specialty dermatology portfolio show that secukinumab, the first IL-17A inhibitor with regulatory submissions completed, had similar efficacy in clearing skin with a convenient pre-filled syringe and autoinjector pen as in the landmark FIXTURE study, where it was significantly superior to Enbrel, a biologic psoriasis therapy approved 10 years ago."
Importantly, in both studies more secukinumab 300 mg patients experienced almost clear skin, described as Psoriasis Area and Severity Index 90 (PASI 90), at Week 12 (60.3 per cent for FEATURE and 55 per cent for JUNCTURE, p<0.0001) compared to placebo. PASI 90 is considered the best evidence of efficacy, and a more robust measure of the extent of skin clearance compared to standard efficacy measures that have been used in most psoriasis clinical studies, such as PASI 75.
The FEATURE and JUNCTURE studies met all primary and pre-specified secondary endpoints. Across the co-primary endpoints in both studies, secukinumab 300 mg demonstrated significant improvements in PASI 75 at Week 12 versus placebo (75.9 per cent vs. 0 per cent for FEATURE; 86.7 per cent vs. 3.3 per cent for JUNCTURE, p<0.0001), and was also superior to placebo according to the Investigator's Global Assessment (IGA mod 2011).
Patients also benefitted from rapid and significant skin clearance with secukinumab in both studies. Already by Week 3, patients taking secukinumab 300 mg experienced superior efficacy in clearing skin compared to placebo. In addition, the 300 mg dose showed numerically and clinically relevant improvements compared to 150 mg.
Both studies measured usability and patient satisfaction with secukinumab delivered via PFS and AI. At Week 1, all patients successfully self-injected secukinumab by following instructions, with no administration issues observed. Patient satisfaction scores were consistently high, showing acceptability of the PFS and AI. Satisfaction was assessed using a self-administered Self-Injection Assessment Questionnaire (SIAQ), which measures overall experience, feelings about injections, self-confidence, satisfaction with self-injection, injection-site reactions, ease of use, and self-image before and after treatment.
Secukinumab demonstrated a positive safety profile consistent with findings from previous studies, with adverse events (AEs) similar between both secukinumab treatment arms (300 mg and 150 mg). In FEATURE, the most common AEs in any treatment group were diarrhea, nasopharyngitis and headache. In JUNCTURE, the most common AEs in any treatment group were nasopharyngitis, headache and pruritus. There were no deaths reported during either study, and no new or unexpected safety findings were observed.
The FEATURE and JUNCTURE results support the head-to-head phase III FIXTURE data first presented in October 2013, which showed secukinumab cleared skin faster and for longer than Enbrel(etanercept). Clinically relevant differences were observed as early as Week 2 in FIXTURE, and by Week 16 nearly three quarters (72 per cent) of secukinumab 300 mg patients experienced almost clear skin (PASI 90). Secukinumab efficacy was also sustained over the full one year study, with significantly more ,00 mg patients experiencing PASI 90 at Week 52 compared to Enbrel (65per cent per cent)
FEATURE and JUNCTURE are the final secukinumab phase III studies to be presented as part of the largest phase III program in moderate-to-severe plaque psoriasis completed to date, which involved more than 3,300 patients in over 35 countries.
FEATURE (First study of sEcukinumAb in pre-filled syringes in subjecTs with chronic plaqUe-type psoriasis REsponse) was a randomized double-blind, placebo-controlled, multicentre phase III study involving 177 subjects with moderate-to-severe plaque psoriasis. In this study, a PFS was introduced into the secukinumab program.
JUNCTURE (Judging the efficacy of secUkinumab in patients with psoriasis using autoiNjector: a Clinical Trial evalUating treatment Results) was a double-blind, placebo-controlled, multicentre phase III study involving 182 subjects with moderate-to-severe plaque psoriasis. In this study, the AI device was introduced into the secukinumab programme.
In both studies, the co-primary endpoints, PASI 75 and IGA mod 2011 at Week 12, were used to demonstrate superiority of secukinumab vs. placebo. Secondary endpoints included PASI 90 at Week 12 and patient satisfaction of secukinumab administered via PFS and AI, determined by a self-administered SIAQ. The trials are continuing up to one year (52 weeks).
FIXTURE (the Full year Investigative eXamination of secukinumab vs. eTanercept Using 2 dosing Regimens to determine Efficacy in psoriasis) was a randomised double-blind, placebo-controlled, multicenter, global pivotal phase III registration study involving 1,306 patients.
Secukinumab (AIN457) is a fully human monoclonal antibody that selectively binds to and neutralizes interleukin-17A (IL-17A)[8]-[10]. IL-17A is a central cytokine (messenger protein) involved in the development of psoriasis, and is found in high concentration in skin affected by the disease. Research shows that IL-17A plays a key role in driving the body's autoimmune response in disorders such as moderate-to-severe plaque psoriasis and is a preferred target for investigational therapies.
Secukinumab is the first therapy selectively targeting IL-17A with phase III results. Regulatory submissions for secukinumab in the EU and US were completed in 2013.
Phase III results for secukinumab in moderate-to-severe plaque psoriasis were first presented in October 2013, with additional results to be presented in 2014 for both moderate-to-severe plaque psoriasis and arthritic conditions (psoriatic arthritis and ankylosing spondylitis). Phase IIIb studies are also ongoing, including the head-to-head study of secukinumab versus Stelara in moderate-to-severe plaque psoriasis (CLEAR) and studies in palmo-plantar psoriasis, nail psoriasis and palmo-plantar pustulosis. Phase II studies are also ongoing in other areas.
Nearly 3 per cent the world's population, or more than 125 million people, are affected by plaque psoriasis with more than one third of these suffering from its moderate-to-severe form. Psoriasis is a chronic autoimmune disease characterised by thick and extensive skin lesions, called plaques, known to cause itching, scaling and pain. This common and distressing disease is not simply a cosmetic problem - even those with very mild symptoms find their condition affects their everyday lives. Psoriasis is also associated with psychosocial effects and those with more severe disease are at a greater risk of death from comorbid diseases such as heart disease and diabetes. Between 40-50 per cent of patients are dissatisfied with their current psoriasis therapies, indicating an unmet need for new therapies that act faster and longer to relieve the debilitating symptoms.