Date: 2014-11-16
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the American College of Rheumatology (ACR) Annual Meeting in Boston
Company: Novartis (Switzerland)
Product: secukinumab (AIN457)
Action
mechanism: monoclonal antibody. Secukinumab (AIN457) is a fully human monoclonal antibody that selectively binds to and neutralizes interleukin-17A (IL-17A). 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.
Disease: psoriatic arthritis
Therapeutic area: Autoimmune diseases – Inflammatory diseases - Rheumatic diseases
Country:
Trial
details: FUTURE 1 and FUTURE 2 are multi-center, randomized, placebo-controlled Phase III studies to evaluate the efficacy of IL-17A inhibition with secukinumab in PsA. In FUTURE 1, patients received an intravenous loading dose of 10 mg/kg every two weeks for the first four weeks of treatment, followed by monthly subcutaneous dose of 75 mg or 150 mg compared to placebo. FUTURE 2 patients received a subcutaneous loading dose of 75 mg, 150 mg, or 300 mg of secukinumab every week for the first four weeks of treatment, followed by the same monthly subcutaneous maintenance dose compared to placebo. The intravenous loading period used in FUTURE 1 was designed to provide high systemic exposure for induction of response, in keeping with the initial proof of concept study in PsA with secukinumab. FUTURE 2 utilized an administration route (subcutaneous loading dose) and dose range (up to 300 mg) that is more consistent with the psoriasis program. A combined total of more than 1,000 patients were enrolled in the studies.
Latest
news: * On November 16, 2014, Novartis announced results from the pivotal Phase III FUTURE 1 and FUTURE 2 studies showing AIN457 (secukinumab) met primary endpoints demonstrating statistically significant improvement of the signs and symptoms of psoriatic arthritis (PsA) versus placebo. PsA is part of a spectrum of long-term diseases impacting joints, known as spondyloarthritis (SpA). There is a high unmet need for new treatment options for patients with PsA and approximately 45% of people are dissatisfied with their treatments. Secukinumab binds to and neutralizes interleukin-17A (IL-17A), which has been shown to play an important role in the development of inflammatory diseases. These results are being presented at the American College of Rheumatology (ACR) Annual Meeting in Boston. Data at ACR presented at ACR showed that statistically significant improvements in signs and symptoms of PsA were achieved with secukinumab versus placebo at Week 24, as measured by a 20% reduction in the American College of Rheumatology (ACR20) response criteria, a standard tool used to assess improvement. Between 50% to 54% of secukinumab patients achieved ACR20 in both FUTURE 1 (p<0.0001) and FUTURE 2 (p<0.0001). This is in comparison to 17.3% and 15.3% of placebo patients who achieved ACR20, respectively. Exploratory analyses in FUTURE 1 showed more secukinumab-treated patients in the 75 mg (20.3%) and 150 mg (20.8%) dose groups experienced ACR20 responses by Week 1 versus placebo (5.4%) (p<0.0001). In FUTURE 2, more secukinumab-treated patients in the 150 mg (42.0%) and 300 mg (37.0%) dose groups experienced ACR20 responses by Week 3 (150 mg p<0.0001;300 mg p<0.001) versus placebo (15.3%); secukinumab-treated patients who received the 75 mg (23.2%) dose did not achieve a statistically significant response. In an additional exploratory analysis in FUTURE 1, a majority of secukinumab-treated patients achieving ACR20 responses at Week 24 also maintained the response at Week 52 with continued treatment. Additional analyses evaluated clinical benefits in patients who had not been previously treated with anti-TNF therapies (anti-TNF naïve) and also in patients who had an inadequate or no response to anti-TNFs. Those who had prior exposure to anti-TNFs included 29.5% (FUTURE 1) and 35.0% (FUTURE 2) of study participants. In FUTURE 1, patients on secukinumab had significantly less progression of joint structural damage compared to placebo, as evaluated by erosion and joint narrowing scores. Improvements in joint damage were shown in both anti-TNF naïve patients and in the patients with inadequate or no response to anti-TNFs. Additionally, secukinumab demonstrated significant improvements in skin psoriasis in both FUTURE 1 and FUTURE 2 compared to placebo. Both studies met their primary endpoint of ACR20 at Week 24: FUTURE 1, 50.5% for secukinumab 75 mg and 50.0% for secukinumab 150 mg versus 17.3% for placebo; p<0.0001 Full results of secondary endpoints will be presented at ACR. Secondary endpoints at Week 24 in FUTURE 1 and FUTURE 2 included: 75% and 90% improvement in Psoriasis Area-and-Severity Index score (PASI 75 and PASI 90) Secukinumab was well tolerated in both studies, with a safety profile generally consistent with that observed in the psoriasis clinical trial program involving nearly 4,000 patients. In FUTURE 1, the most common adverse events (AEs) were nasopharyngitis, headache, upper respiratory tract infection, hypercholesterolaemia (increased lipid levels), and nausea. In FUTURE 1, 60.4% (75 mg), 64.9% (150 mg) and 58.4% (placebo) of patients reported an AE. Serious adverse event (SAE) rates were 2.5%, 4.5%, and 5.0%, respectively. In FUTURE 2, the most common AEs were upper respiratory tract infection, nasopharyngitis, headache, nausea, diarrhea, and urinary tract infection. In FUTURE 2, 53.8% of patients in the pooled secukinumab group and 58.2% in the placebo group reported an AE. SAE rates were 3.3% and 2.0%, respectively. Global regulatory applications for secukinumab in PsA are planned for 2015. This follows the secukinumab global regulatory applications for moderate-to-severe plaque psoriasis which were filed in October 2013 with approvals anticipated in late 2014 or early 2015. In addition to PsA, secukinumab is also in clinical trials for the treatment of ankylosing spondylitis (AS) and rheumatoid arthritis (RA). Following the presentation of the first moderate-to-severe plaque psoriasis Phase III results of secukinumab in October 2013, EU and US regulatory filings were submitted at the end of 2013.
FUTURE 2, 29.3% for secukinumab 75 mg (p<0.05); 51.0% and 54.0% for secukinumab 150 mg and 300 mg, respectively, versus 15.3% for placebo; p<0.0001
Change from baseline in 28-joint Disease Activity Score using C-reactive protein (DAS28 – CRP)
Physical function assessed using the Medical Outcome Short Form (36) Health Survey physical component summary scores (SF-36 PCS)
Physical function assessed using the Health Assessment Questionnaire Disability Index (HAQ-DI)
ACR50 response
Proportion of subjects with dactylitis and enthesitis
Overall safety and tolerability of each secukinumab regimen compared with placebo
