Date: 2015-03-21
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the 73rd Annual Meeting of the American Academy of Dermatology (AAD) in San Francisco, USA
Company: Novartis (Switzerland)
Product: Cosentyx® - secukinumab (AIN457)
Action
mechanism: monoclonal antibody. Secukinumab (AIN457) is a fully human monoclonal antibody that selectively binds to and neutralizes interleukin-17A (IL-17A). 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 to publish phase III results. Regulatory submissions for secukinumab in the EU and US were completed in 2013. In January 2015, Cosentyx® (at a dose of 300 mg) became the first and only IL-17A inhibitor approved in Europe as a first-line systemic treatment of moderate-to-severe plaque psoriasis in adult patients, and in the US as a treatment for moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy (light therapy). In addition to the EU and the US, Cosentyx® has been approved in Switzerland, Chile, Australia, Canada and Singapore for the treatment of moderate-to-severe plaque psoriasis and in Japan for the treatment of moderate-to-severe plaque psoriasis and active psoriatic arthritis (PsA). Cosentyx® is also in Phase III development for PsA and ankylosing spondylitis; global regulatory applications are planned for 2015.
Disease: psoriasis
Therapeutic area: Autoimmune diseases - Dermatological diseases
Country: ERASURE : Argentina, Canada,Colombia, Estonia, Iceland, Israel, Japan, Latvia, Lithuania, Mexico, Taiwan, USA FIXTURE : Australia, Belgium, Canada, Egypt, Finland, France, Germany, Guatemala, Hungary, Iceland, India, Italy, Republic of Korea, Philippines, Poland, Romania,Russian Federation, Singapore, Sweden,Turkey, UK, USA
Trial
details: ERASURE (Efficacy of Response And Safety of two fixed secUkinumab REgimens in psoriasis - NCT01365455) and FIXTURE (the Full year Investigative eXamination of secukinumab vs. eTanercept Using 2 dosing Regimens to determine Efficacy in psoriasis -NCT01358578) are part of a 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 vs. placebo. 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 vs. Enbrel 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.
The A2302E1 Extension Study (Cosentyx Extension Study to the FIXTURE and ERASURE studies) is a multicenter, double-blind, randomized withdrawal extension study to the FIXTURE and ERASURE pivotal Phase III studies. The extension study was conducted to collect long term efficacy, safety and tolerability data on Cosentyx in patients who achieved a PASI 75 response to Cosentyx at Week 52 of the FIXTURE and ERASURE core studies in moderate-to-severe plaque psoriasis.
Patients who had been receiving Cosentyx 300 mg or 150 mg during the maintenance period of the core studies, and who exhibited a PASI 75 response at Week 52 of the core studies, were randomized to continue the same Cosentyx dose or receive placebo. Patients who exhibited partial response (PASI 50 to
Latest
news: * On March 21, 2015, Novartis announced new two-year results demonstrating strong and sustained efficacy with Cosentyx® (secukinumab) with a favorable safety profile for the treatment of psoriasis patients. The data comes from the extension study of the pivotal Phase III FIXTURE and ERASURE trials. Results were presented for the first time in a late-breaking session at the 73rd Annual Meeting of the American Academy of Dermatology (AAD) in San Francisco, USA. In this extension of the FIXTURE and ERASURE studies, 995 patients who achieved Psoriasis Area Severity Index (PASI) 75 response after a year of therapy (Week 52) received either Cosentyx 300 mg, Cosentyx 150 mg or placebo for an additional year (Week 104). After two full years of therapy, 7 out of 10 (71%) patients treated with Cosentyx 300 mg had clear or almost clear skin (PASI 90); 4 out of 10 (44%) had clear skin (PASI 100) and almost 9 out of 10 (88%) patients maintained their PASI 75 response. PASI assesses treatment efficacy by measuring the reduction in redness, scaling and thickness of psoriatic plaques and the extent of involvement in each region of the body. In the study, 70% of patients who initially received placebo and were switched to receive Cosentyx 300 mg after losing treatment response, were able to achieve PASI 90 within 12 weeks of starting Cosentyx treatment[1]. The safety profile of Cosentyx was favorable and consistent with previously reported Phase III clinical trials. No new or unexpected safety findings were identified during the two year extension. The most common adverse were nasopharyngitis, upper respiratory tract infection, hypertension, headache and arthralgia. 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 Cosentyx vs. placebo (p * On July 9, 2014, Novartis announced that detailed results from two pivotal phase III studies evaluating the interleukin-17A (IL-17A) inhibitor secukinumab (AIN457) were published online in the New England Journal of Medicine (NEJM - Langley RG, Elewski BE, Lebwohl M, et al. Secukinumab in plaque psoriasis: results of two phase three trials. New Engl J Med. 2014 [published online ahead of print 9 July 2014]). Secukinumab met all primary and key secondary endpoints at Week 12 in the ERASURE and FIXTURE studies, showing superiority to Enbrel®* (etanercept) 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<0.001). In comparison, only 20.7% of Enbrel-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 also show that secukinumab-treated patients had their symptoms resolved faster than those treated with Enbrel 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 Enbrel® 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[1]. In both studies, the incidence of adverse events (AEs) 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 AEs in the secukinumab groups during induction and the entire 52-week treatment period in FIXTURE were comparable with Enbrel®. 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 CLEAR study of secukinumab versus Stelara® in moderate-to-severe plaque psoriasis and studies in palmo-plantar psoriasis, nail psoriasis and palmo-plantar pustulosis. Phase II studies are also ongoing in other indications. * On October 3, 2013, Novartis has announced results from the head-to-head Phase III FIXTURE study showing secukinumab (AIN457) was significantly superior to Enbrel® (etanercept) in moderate-to-severe plaque psoriasis. These new 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. The study 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 Enbrel patients. Secukinumab 300 mg patients were also more likely to experience completely clear skin compared to those taking Enbrel 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 Enbrel 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 Enbrel 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 Enbrel (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 Enbrel. The most common AEs 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 AEs (SAEs) were experienced by 6% of secukinumab 300 mg, 5% of secukinumab 150 mg and 6% of Enbrel 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[2]-[4]. Research shows 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. * On July 8, 2013, Novartis has announced top-line results from the head-to-head Phase III psoriasis study which showed the superiority of secukinumab (AIN457) in clearing skin to Enbrel® (etanercept), an anti-tumor necrosis factor (anti-TNF) therapy. In addition, secukinumab (AIN457) met all primary and secondary endpoints. Full results from the secukinumab (AIN457) Phase III study program are expected to be presented at major medical congresses later this year. In the FIXTURE study, the observed safety profile of secukinumab (AIN457) was consistent with previously reported results from Phase II studies in moderate-to-severe plaque psoriasis and no new safety concerns were identified.
