Date: 2015-06-10
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the European League Against Rheumatism Annual Congress (EULAR 2015), in Rome, Italy
Company: Novartis (Switzerland)
Product: Cosentyx® (secukinumab) (AIN457)
Action
mechanism: monoclonal antibody. Secukinumab (AIN457) is a fully human monoclonal antibody being investigated for diseases that affect the immune system. Secukinumab stops a protein called interleukin-17A (IL-17A), a protein that is central to the development of inflammatory diseases, including ankylosing spondylitis. Cosentyx® (secukinumab) has been approved for the treatment of adults with active ankylosing spondylitis in January 2016 in the US and in November 2015 in the EU.
Disease: ankylosing spondylitis
Therapeutic area: Autoimmune diseases – Inflammatory diseases - Rheumatic diseases
Country:
Trial
details: MEASURE 1 and MEASURE 2 are multi-center, randomized, placebo-controlled Phase III studies to evaluate the efficacy of IL-17A inhibition with secukinumab in AS compared to placebo, and to assess the safety, tolerability, and effectiveness in patients with AS. Both MEASURE 1 and MEASURE 2 evaluated secukinumab 75 mg and 150 mg versus placebo. In the MEASURE 1 study patients received an intravenous loading dose of 10 mg/kg every two weeks for the first four weeks of treatment followed by monthly subcutaneous doses that aimed to provide high exposure for induction of response in order to confirm the clinical benefit observed in an initial proof-of-concept study. MEASURE 2 evaluated subcutaneous loading regimens. MEASURE 2 is a randomized, double-blind, Phase III study evaluating the efficacy and safety of secukinumab versus placebo in subjects with active AS. A total of 219 patients were randomized to receive subcutaneous secukinumab (150 or 75 mg) or placebo at baseline, Week 1, 2 and 3 and every 4 Weeks starting at Week 4. This differed from the MEASURE 1 study, in which patients received an intravenous loading dose of secukinumab followed by monthly subcutaneous doses. At Week 16, subjects in the placebo group were re-randomized to secukinumab 150 mg or 75 mg every 4 weeks. In total, 181 (82.6%) of patients completed one year of treatment.
Latest
news: * On June 10, 2015, Novartis announced new one-year study results from the MEASURE 2 pivotal Phase III study of secukinumab in ankylosing spondylitis (AS). Data from the study demonstrated that approximately 74% of patients achieved clinically significant improvement in their symptoms after one year of treatment, as measured by ASAS20, a standard tool used to assess clinical improvement in AS. Detailed study results will be presented at the European League Against Rheumatism Annual Congress (EULAR 2015), in Rome, Italy. * On November 15, 2014, Novartis announced results from the MEASURE 1 and MEASURE 2 pivotal Phase III studies of AIN457 (secukinumab) in ankylosing spondylitis (AS). In the studies, secukinumab met the primary endpoint demonstrating statistically significant improvements versus placebo in the signs and symptoms of AS. Detailed study results will be presented during a plenary session (MEASURE 1) and in a poster presentation (MEASURE 2) at the American College of Rheumatology (ACR) Annual Meeting in Boston. Statistically significant improvements in signs and symptoms of AS were achieved with secukinumab versus placebo at Week 16, as measured by at least 20% improvement in the Assessment of Spondyloarthritis International Society criteria (ASAS20), a standard tool used to assess clinical improvement in AS. More than 60% of secukinumab 150 mg treated patients achieved an ASAS20 response in MEASURE 1 (p<0.0001) and MEASURE 2 (p<0.001). This is in comparison to 28.7% and 28.4% of placebo patients who achieved an ASAS20 response in MEASURE 1 and MEASURE 2, respectively. Both studies met their primary endpoint of ASAS20 (a >20% improvement of at least one unit in each of three domains, with no worsening in the fourth domain) in at least one study dose arm of secukinumab: MEASURE 1: 60.8% and 59.7% for secukinumab 150 mg and 75 mg, respectively, versus 28.7% for placebo; p<0.0001 Full results of secondary endpoints will be presented at ACR. Secondary endpoints at Week 16 for MEASURE 1 and MEASURE 2 included: ASAS40 response (a >40% improvement of at least two units in each of three domains, with no worsening in the fourth domain) In exploratory analyses, secukinumab 150 mg treated patients experienced ASAS20 responses at Week 1 in both studies (p<0.01, MEASURE1; p<0.05, MEASURE 2) and were sustained through 52 weeks of treatment, according to data from MEASURE 1. Additionally, statistically significant improvements in ASAS20 at Week 16 with secukinumab 150 mg were observed, compared to placebo (p<0.05) in patients who had not been previously treated with anti-TNF therapies (anti-TNF naïve) and also in patients who had an inadequate response or intolerance to anti-TNFs. In both studies, treatment with secukinumab 150 mg resulted in significant improvements in physical function and quality of life at Week 16 versus placebo (p<0.05), as measured by the SF-36 Physical Component Summary (PCS) and ASQoL (AS quality of life), with improvements sustained through 52 weeks of treatment in MEASURE 1. Secukinumab was well tolerated in both studies, with a safety profile consistent with that observed in the psoriasis clinical trial program involving nearly 4,000 patients. In MEASURE 1, the most common adverse events (AEs) were nasopharyngitis, dyslipidemia (imbalance of fats circulating in the blood stream), headache, nausea, and leukopenia (low white blood cell count). In MEASURE 1, 66.9% of secukinumab 75 mg patients and 69.6% of secukinumab 150 mg patients experienced an AE compared to 55.7% of placebo patients. Serious adverse event (SAE) rates were 1.6% (75 mg), 2.4% (150 mg), and 4.1% (placebo). In MEASURE 2, the most common AEs were nasopharyngitis, headache, and influenza. In MEASURE 2, 57.5% of secukinumab 75 mg patients and 62.5% of secukinumab 150 mg patients experienced an AE compared to 63.5% of placebo patients. SAE rates were 5.5% (75 mg), 5.6% (150 mg), and 4.1% (placebo). * On October 23, 2014, Novartis announced that AIN457 (secukinumab) met primary and key secondary endpoints in two pivotal Phase III studies (MEASURE 1 and MEASURE 2) in patients with ankylosing spondylitis (AS). Key endpoints included improvements in signs and symptoms of the disease versus placebo and associated improvements in physical function and quality of life. MEASURE 1 and MEASURE 2 enrolled a combined total of approximately 600 patients. Detailed results of the studies will be presented at an upcoming medical congress. Joint regulatory applications for secukinumab in ankylosing spondylitis and psoriatic arthritis are planned for 2015. This follows the secukinumab global regulatory applications for moderate-to-severe plaque psoriasis which were filed in October 2013 with regulatory decisions anticipated in late 2014 or early 2015.
In MEASURE 2, patients treated with secukinumab 150 mg achieved significantly higher ASAS20 versus placebo at Week 16 (61.1% vs 28.4%; p<0.001). New data at one year show that improvements in the signs and symptoms of AS were sustained through 52 weeks of treatment, confirming data from the MEASURE 1 study. In MEASURE 2, 73.8% of patients achieved ASAS20 response at one year along with associated improvements in physical function and health-related quality of life. Secukinumab was well tolerated in MEASURE 2, with a safety profile consistent with that observed in the psoriasis clinical trial program involving nearly 4,000 patients. The most common adverse events (AEs) were upper respiratory tract infection and headache.
MEASURE 2 trial met its primary endpoint of ASAS20 response at Week 16, which was significantly higher with secukinumab 150 mg versus placebo (61.1% vs 28.4%; p<0.001), with improvements observed by Week 1, and sustained through one year of treatment (ASAS20=73.8%).[1] Secukinumab 150 mg also significantly improved ASAS40, hsCRP, ASAS 5/6, BASDAI, SF-36 PCS and ASQoL compared with placebo at Week 16, with improvements sustained through 1 year. Secukinumab 75 mg did not meet any of the pre-defined primary or secondary endpoints.
MEASURE 2: 61.1% and 41.1% for secukinumab 150 mg and 75 mg, respectively, versus 28.4% for placebo; p
High sensitivity C-reactive protein (hs-CRP)
ASAS 5/6 responses (>20% improvement in five of six domains, adding spinal mobility and C-reactive protein [CRP], with no worsening in the sixth domain)
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), ASAS partial remission (a score of BASDAI, quality of life assessed using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the ASQoL, and ASAS partial remission
