The results from the head-to-head phase III FIXTURE study showing Secukinumab ( AIN457 ), an interleukin-17A ( IL-17A ) inhibitor, was significantly superior to Etanercept ( Enbrel ) in moderate-to-severe plaque psoriasis.
Etanercept is a current standard-of-care anti-TNF medication approved to treat moderate-to-severe plaque psoriasis.
The results were presented at the 22nd Congress of the European Association of Dermatology and Venereology ( EADV ) in Istanbul, Turkey.
The pivotal FIXTURE study met all primary and pre-specified key secondary endpoints ( p less than 0.0001 for placebo comparisons and p=0.0250 for Etanercept comparisons ).
Both doses of Secukinumab showed improved efficacy to Etanercept throughout the 52 week study, beginning as early as Week 2 and confirmed by Week 12 when the primary endpoints were assessed.
More Secukinumab patients experienced almost clear skin ( PASI 90 ) and completely clear skin ( PASI 100 ) compared to Etanercept, which are higher standards of skin clearance compared to the standard efficacy measures used in most psoriasis clinical studies.
FIXTURE has compared two doses of Secukinumab ( 300 mg and 150 mg ) with Etanercept 50 mg and placebo. The co-primary endpoints were assessed at week 12 and compared Secukinumab efficacy versus placebo according to the Psoriasis Area and Severity Index 75 ( PASI 75 ) and the Investigator's Global Assessment ( IGA mod 2011 ).
The study has also showed that 72% of Secukinumab 300 mg patients experienced at least a 90% reduction in skin redness, thickness and scaling ( PASI 90 ) by week 16 of the study. More than half ( 54% ) of Secukinumab 300 mg patients achieved PASI 90 as early as week 12, compared to 21% of Etanercept patients. Secukinumab 300 mg patients were also more likely to experience completely clear skin compared to those taking Etanercept in the study, as measured by PASI 100 at week 12 ( 24% versus 4% ).
Secukinumab-treated patients also had their symptoms resolved faster than those treated with Etanercept in the 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 8 for Etanercept patients.
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% ).
There were no major safety signals identified in FIXTURE or the broader Secukinumab phase III clinical trial program in moderate-to-severe plaque psoriasis.
In FIXTURE, the incidence of adverse events ( AEs ) was similar between both Secukinumab treatment arms ( 300 mg and 150 mg ), and was comparable to Etanercept.
The most common adverse effects in any treatment group ( including placebo ) throughout the 52 week treatment period were nasopharyngitis and headache ( occurring in between 12-36 patients per 100 patient years in all groups ).
At the same time point, serious adverse events were experienced by 6% of Secukinumab 300 mg, 5% of Secukinumab 150 mg and 6% of Etanercept patients.
There were no deaths reported during the study.
Secukinumab is the first therapy selectively targeting IL-17A to have phase III results presented. IL-17A is a central cytokine ( messenger protein ) involved in the development of psoriasis, and is found in high concentrations in psoriasis skin plaques.
The research has shown that IL-17A, in particular, 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. ( Xagena )
Source: Novartis, 2013