Results from two pivotal phase III studies evaluating the interleukin-17A ( IL-17A ) inhibitor Secukinumab ( AIN457 ) were published in the New England Journal of Medicine ( NEJM ).
Secukinumab met all primary and key secondary endpoints at week 12 in the ERASURE and FIXTURE studies, showing superiority to Etanercept ( Enbrel ) in improving moderate-to-severe plaque psoriasis symptoms in the FIXTURE study, and superiority over placebo in both studies.
Over half of Secukinumab 300 mg patients experienced clear ( PASI 100 ) or almost clear ( PASI 90 ) skin, described as Psoriasis Area and Severity Index 90 or 100 ( PASI 90/PASI 100 ) by week 12 ( 59.2% for ERASURE and 54.2% for FIXTURE, p less than 0.001 ).
In comparison, only 20.7% of Etanercept-treated patients experienced PASI 90 or 100 in FIXTURE.
Secukinumab 300 mg patients' response continued to improve from week 12, with more than 70% experiencing clear or almost clear skin by week 16 ( 72.4% and 36.8% for PASI 90 and 100, respectively ) in the FIXTURE study, which was maintained in the majority of patients up to week 52 ( with continued treatment ).
Data published in NEJM have also shown that Secukinumab-treated patients had their symptoms resolved faster than those treated with Etanercept in the FIXTURE study.
Clinically relevant differences were observed as early as week 2, and on average Secukinumab 300 mg patients had their symptoms halved by week 3, compared to week 7 for Etanercept patients.
In addition to high rates of clear to almost clear skin, Secukinumab patients also reported superior improvements in itching, pain and scaling, compared to placebo at week 12, in ERASURE. Similarly, health-related quality of life ( HRQoL ) was significantly improved among Secukinumab-treated patients at week 12 compared to placebo in both studies, as assessed by the Dermatology Quality of Life Index ( DLQI ).
The effect of psoriasis on quality of life has been shown to be similar to diseases such as cancer, heart disease, arthritis, type 2 diabetes and depression.
In ERASURE and FIXTURE Secukinumab exhibited an acceptable safety profile consistent with phase II studies. In both studies, the incidence of adverse events was similar between both Secukinumab treatment arms ( 300 mg and 150 mg ), and were slightly higher than in the placebo group during the 12-week induction period, mostly consisting of mild to moderate upper respiratory tract infections.
Incidences of adverse reactions in the Secukinumab groups during induction and the entire 52-week treatment period in FIXTURE were comparable with Etanercept.
ERASURE ( Efficacy of Response And Safety of two fixed secUkinumab REgimens in psoriasis ) and FIXTURE ( the Full year Investigative eXamination of secukinumab vs. eTanercept Using 2 dosing Regimens to determine Efficacy in psoriasis ) are 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.
ERASURE and FIXTURE assessed the efficacy, safety and tolerability of induction period ( at week 12 ) and maintenance therapy ( at week 52 ) with subcutaneous Secukinumab 300 mg or 150 mg in patients with moderate-to-severe plaque psoriasis. Both studies were multicenter, randomized, double-blind, placebo-controlled ( FIXTURE: also active controlled ), parallel-group phase III trials involving 738 patients and 1,306 patients with moderate-to-severe plaque psoriasis, respectively. Each study consisted of a 1-to-4-week screening period, a 12-week induction period, a 40-week maintenance period and an 8-week follow-up period. FIXTURE is the first full-year blinded, direct comparison of biologic therapies for psoriasis in a phase III study.
The co-primary endpoints in both studies, PASI 75 response and Investigator's Global Assessment ( IGA mod 2011 ) 0/1 response at week 12, were used to demonstrate superiority of Secukinumab versus placebo ( p less than 0.001 for all comparisons ).
Secukinumab 300 mg demonstrated significant improvements in PASI 75 at week 12 ( 81.6% vs. 4.5% for placebo in ERASURE and 77.1% vs. 44.0% for Etanercept vs. 4.9% for placebo in FIXTURE ).
Secukinumab 300 mg was also superior to comparator arms in IGA mod 2011 0/1 response at week 12. Response over time suggests that PASI and IGA response rates improved from week 12 to week 16 and then maintained after week 16.
The 300 mg dose showed numerically and clinically relevant improvements compared to 150 mg in both studies.
Key secondary endpoints in both studies included comparisons with placebo according to PASI 90 at week 12, patient-reported outcomes of itching, pain and scaling from the Psoriasis Symptom Diary at week 12 and HRQoL according to the DLQI.
In addition, the FIXTURE study assessed Secukinumab superiority versus Etanercept across several measures including PASI 90 at week 12, maintenance of PASI 75 from week 12 to week 52, and maintenance of IGA mod 2011 0/1 from week 12 to week 52. ( Xagena )
Source: Novartis, 2014