Novartis has started patient enrollment in a new phase IIIb head-to-head study of IL-17A inhibitor secukinumab (AIN457) versus Stelara (ustekinumab) in moderate-to-severe plaque psoriasis. A total of twenty-five secukinumab abstracts, including two pivotal phase III convenience studies to be presented for the first time, will be unveiled at the 72nd Annual Meeting of the American Academy of Dermatology (AAD), taking place in Denver, Colorado, USA from 21-25 March 2014.
"We are pleased to announce the start of CLEAR, our global phase IIIb head-to-head psoriasis study of secukinumab versus Stelara at the 2014 AAD annual meeting, which will provide further evidence regarding the benefit IL-17A inhibitor secukinumab brings to patients," said Tim Wright, global head of development, Novartis Pharmaceuticals. "We initiated this study following the positive results from the phase III FIXTURE study, which showed secukinumab was significantly superior to Enbrel in clearing skin, and we look forward to presenting additional new phase III data from our specialty dermatology portfolio at AAD."
Nearly 3 per cent of 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. Between 40-50 per cent of patients are dissatisfied with their current psoriasis therapies, indicating an unmet need for convenient therapies that act faster and longer to relieve the debilitating symptoms.
CLEAR (Comparison to assess Long-term Efficacy, safety and tolerability of secukinumab vs. ustekinumab), the new 52-week, multicenter, randomised, double-blind study, is the second head-to-head phase III study initiated with secukinumab, and will compare the long-term safety, tolerability and efficacy of secukinumab versus Stelara, a current standard-of-care therapy, in patients with moderate-to-severe plaque psoriasis. The target enrollment for this global phase IIIb study is approximately 640 patients with sites in 25 countries across North America, Europe, Asia and Australia.
The primary endpoint measured at Week 16 is at least 90 per cent reduction in the severity of psoriasis symptoms (redness, thickness and scaling) and the extent of skin affected by the disease, known as Psoriasis Area and Severity Index (PASI) 90. PASI 90 is considered the best evidence of efficacy and is therefore a more robust measure of the extent of skin clearance compared to the standard efficacy measures used in most psoriasis clinical studies.
The CLEAR study follows the pivotal phase III head-to-head Fixture study, which showed secukinumab was significantly superior to Enbrel in clearing skin. Enbrel is a current standard-of-care anti-TNF-alpha medication approved to treat moderate-to-severe plaque psoriasis, and results from the FIXTURE study were first announced in October 2013.
Secukinumab (AIN457) is a fully human monoclonal antibody that selectively binds to and neutralises interleukin 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, based on the largest phase III programme in moderate-to-severe plaque psoriasis completed to date, which involved more than 3,300 patients in over 35 countries.
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 of 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.