Date: 2012-09-27
Type of information: Results
phase: 2
Announcement: results
Company: Novartis (Switzerland)
Product: secukinumab (AIN457)
Action
mechanism: AIN457 is a fully human monoclonal antibody inhibiting interleukin-17A (IL-17A), a key pro-inflammatory cytokine. Proof-of-concept and Phase II studies in moderate-to-severe plaque psoriasis and arthritic conditions (psoriatic arthritis, ankylosing spondylitis and rheumatoid arthritis) have suggested that AIN457 may provide a new mechanism of action for the treatment of immune-mediated diseases.
Disease: psoriasis
Therapeutic area: Autoimmune diseases – Dermatological diseases
Country:
Trial
details: Data are based on a double-blind, parallel group, placebo-controlled Phase II study involving 404 patients, which met its primary endpoint of PASI 75 (Psoriasis Area and Severity Index) responses at Week 12. It was designed to evaluate the safety and efficacy of AIN457 in different regimens (weekly for the first month; once every four weeks; or single dose) of 150 mg given subcutaneously.
The undertaken sub-analyses included assessment of AIN457 treatment efficacy in 131 patients with hand and/or foot psoriasis, often described as palmoplantar psoriasis. All 404 patients were involved in assessing health-related quality of life, and data from 304 patients were used to assess AIN457 treatment efficacy in nail psoriasis.
Latest
news: * On September 27, 2012, Novartis has announced new Phase II data showing AIN457 (secukinumab) may significantly improve moderate-to-severe plaque psoriasis on the hands, feet and nails when used every week for the first month of treatment, compared to placebo. Additional analysis on patients with moderate-to-severe plaque psoriasis also showed that AIN457 may successfully improve quality of life by Week 12 in the study.The results have been presented at the European Academy of Dermatology and Venereology (EADV) 21st Congress, in Prague, Czech Republic. They provide additional insight into the safety and efficacy of AIN457, following the presentation of the study's primary endpoint at EADV in 2011 (See below). The new data from the sub-analyses undertaken on the Phase II study show AIN457 was nearly three times more effective than placebo at reducing moderate-to-severe plaque psoriasis on the hands and/or feet when given every week during the first month of treatment (54.3% of patients vs. 19.2% respectively, p=0.005), as measured by the Investigator\'s Global Assessment (IGA). Patients also benefited if they received AIN457 once every four weeks, with 39.0% experiencing either \"clear\" or \"minimal\" psoriasis after 12 weeks of treatment[1]. Another analysis found that these AIN457 treatment schedules also notably reduced the signs and symptoms of finger nail psoriasis compared to placebo.
The study safety analysis of these data showed a comparable safety profile between treatment and placebo, with the most common adverse events (AEs) observed being infections.
Other new data presented at EADV in the total moderate-to-severe plaque psoriasis study population show that AIN457 improved skin-related quality of life in 25 times more patients after 12 weeks of treatment when given every week for the first month, compared to placebo (40.8% vs. 1.6%, p<0.001), as measured by the Dermatology Life Quality Index (DLQI)[8]. In this same treatment group, significantly more patients experienced improvements in pain and discomfort compared to placebo (36.2% vs. -1.5%) from baseline; and in anxiety and depression versus placebo (16.3% vs. 6.2%), as measured by EuroQol (EQ-5D). The effect of psoriasis on patients\' health-related quality of life has been shown to be similar to diseases such as cancer, heart attack, arthritis, type 2 diabetes and depression.
All core pivotal trials for AIN457 in moderate-to-severe plaque psoriasis are on track, involving more than 3,000 patients worldwide, and indicating a high interest from both medical and patient communities. Phase III data in moderate-to-severe plaque psoriasis is expected in 2013, with regulatory submissions to follow shortly thereafter.
The Phase III programs for these potential indications are ongoing, and first interpretable results are expected in 2013 for moderate-to-severe plaque psoriasis and in 2014 for arthritic conditions. Phase II studies are also ongoing in other areas, including multiple sclerosis.
* On October 24, 2011, Novartis has announced positive results from three Phase II trials showing that AIN457 (secukinumab) produced a quick and significant improvement of symptoms in patients with moderate-to-severe plaque psoriasis. The results were presented at the annual European Academy of Dermatology and Venereology (EADV) Congress, in Lisbon, Portugal.
The three double-blind, parallel group, placebo-controlled Phase II studies presented at EADV were designed to evaluate the safety and efficacy of AIN457 in different doses and administration regimens. The primary endpoints of the studies were PASI 75 responses at Week 12, with PASI 90 responses at Week 12 among the secondary endpoints. The primary endpoint was met for one or more of the doses (25, 75 and 150 mg, subcutaneously; 3 mg/kg, 10mg/kg and 3x10mg/kg, intravenously) and regimens (Early, Monthly and Single) studied in each trial. In all three studies, 60% of patients experienced adverse events with AIN457 in the first twelve weeks compared to 61% with placebo. Serious adverse events were reported in 3% of AIN457 patients vs 1% with placebo.
In one study, 81% of patients receiving AIN457 150mg subcutaneously once a month experienced at least a 75% improvement of psoriasis signs and symptoms as measured by PASI (Psoriasis Area and Severity Index) vs 9% for placebo at week 12 (p<0.001).
In another study, results also showed that 83% of patients who were given an intravenous starting dose of AIN457 experienced at least a 75% improvement of symptoms vs 10% for placebo. A third study showed that receiving AIN457 in the first month was beneficial to 55% of patients vs 2% for placebo at week 12 (p<0.001).
Larger-scale and longer-term Phase III studies with AIN457 have already began this year.
