Secukinumab is the first therapy that selectively targets IL-17A in psoriasis to complete a Phase III trial.
Novartis announced last week
that secukinumab had demonstrated “significantly superior” efficacy over Enbrel (etanercept) in patients with moderate-to-severe plaque psoriasis.
The products were compared in a head-to-head Phase III trial, and according to a presentation at the 22nd Congress of the European Association of Dermatology and Venereology in Istanbul, secukinumab met all of its primary and secondary endpoints.
The FIXTURE study enrolled more than 3300 patients and was part of the largest clinical program to study moderate-to-severe plaque psoriasis. It compared 2 dosing levels (300 mg and 150 mg) of secukinumab with Enbrel (50 mg) and placebo over 52 weeks. The efficacy of each drug was analyzed using the Psoriasis Area and Severity Index 75 (PASI 75) and the Investigator’s Global Assessment.
Both doses of secukinumab demonstrated improved efficacy over Enbrel throughout the duration of the study, beginning as early as week 2. Notably, more secukinumab patients experienced almost clear skin (described as PASI 90) and completely clear skin (PASI 100) compared with Enbrel. According to a Novartis press release, these are “higher standards of skin clearance compared to the standard efficacy measures used in most psoriasis clinical studies.”
By week 16 of the study, 72% of secukinumab 300 mg patients saw a 90% reduction in skin redness, thickness, and scaling. Participants who were taking secukinumab also experienced results much more quickly—at week 12, more than half (54%) of secukinumab 300 mg patients achieved PASI 90,compared with just 21% of Enbrel patients. In addition, 24% of patients on secukinumab experienced completely clear skin (PASI 100) at week 12 compared with just 4% of those taking Enbrel.
Unlike many of the tumor necrosis factor (TNF) inhibitors used to treat psoriasis, secukinumab employs a unique first-in-class mechanism of action. The drug targets the function of proinflammatory cytokine IL-17A, a messenger protein typically found in high concentrations in psoriasis skin plaques. IL-17A recruits monocytes and neutrophils to the site of inflammation, and psoriasis patients’ skin is in a constant state of inflammation as a result of this IL-17A activity. Secukinumab works by neutralizing the function of this interleukin.
Assuming secukinumab goes on to win FDA approval, it is likely to have a significant impact on clinical decisions and payer policies, as Enbrel is currently considered the standard of care to treat psoriasis and was recently found
to be the most commonly used drug among TNF inhibitors. But even with enhanced head-to-head pharmacoeconomic trial data, a shift in clinical prescribing behaviors would depend on secukinumab’s cost. Given the apparently superior efficacy of secukinumab, Novartis may ultimately set its price higher than that of etanercept, which is approximately $17,270 per treated patient per year.