Taltz progress in COAST-V and COAST-W trials for ankylosing spondylitis.- Eli Lilly

Eli Lilly and Company announced that the company will present positive findings from two Phase III studies, COAST-V and COAST-W , in adults with ankylosing spondylitis (AS), also referred to as radiographic axial spondyloarthritis (axSpA), at the American College of Rheumatology (ACR)/Association of Rheumatology Health Professionals (ARHP) Annual Meeting in Chicago on October 23. The analyses are part of a clinical development program that aims to evaluate Taltz (ixekizumab) across various populations of patients with AS.

In both studies, Taltz demonstrated a statistically significant and clinically meaningful improvement in proportion of patients who achieved Assessment of Spondyloarthritis International Society 40 (ASAS40) over 16 weeks compared to placebo. ASAS40 represents at least a 40-percent improvement in disease signs and symptoms such as pain, inflammation and function. COAST-V is the first successful trial in AS to use ASAS40, a stringent clinical measure indicating a high degree of clinical improvement as the primary endpoint, compared to the standard endpoint of ASAS20. COAST-W is the first AS study to specifically focus on the difficult-to-treat population of patients who had an inadequate response to one or two tumor necrosis factor (TNF) inhibitors (90 percent of enrolled patients) or intolerance to a TNF inhibitor (10 percent).

COAST-V Analysis of Study Results : COAST-V, which included 341 patients, is the first Phase III study of Taltz among patients with AS who had never received a biologic disease-modifying anti-rheumatic drug (bDMARD). It also is the first study to include both a placebo control arm and active reference arm (adalimumab). During the study, patients were treated with 80 mg of Taltz subcutaneously either every four weeks or every two weeks (following 80 mg or 160 mg starting dose at Week 0), adalimumab, or placebo.At 16 weeks, 48 percent of patients treated with Taltz every four weeks, 52 percent of patients treated with Taltz every two weeks and 18 percent of patients treated with placebo achieved ASAS40, the primary endpoint of the study. Taltz also demonstrated a statistically significant improvement on the following secondary endpoints, achieving the following response rates at 16 weeks: ASAS20: 64 percent of patients treated with Taltz every four weeks, 69 percent of patients treated with Taltz every two weeks and 40 percent of patients treated with placebo achieved ASAS20. BASDAI50: 42 percent of patients treated with Taltz every four weeks, 43 percent of patients treated with Taltz every two weeks and 17 percent of patients treated with placebo achieved a Bath Ankylosing Spondylitis Disease Activity Index 50 (BASDAI50). MRI Spine SPARCC CFB: patients treated with Taltz every four weeks experienced a -11.0 change from baseline (CFB) in MRI spine SpA Research Consortium of Canada (SPARCC) score, patients treated with Taltz every two weeks experienced a -9.6 SPARCC CFB and patients treated with placebo experienced a -1.5 SPARCC CFB. "Taltz demonstrated significant improvements in disease activity, functional disability, and spinal and sacroiliac joint inflammation among patients with AS," said D�sir�e van der Heijde, M.D., Ph.D., professor of rheumatology at Leiden University Medical Center.

COAST-W Analysis of Study Results : COAST-W is a Phase III study of 316 patients with AS who had an inadequate response or were intolerant to one or two tumor necrosis factor (TNF) inhibitors. COAST-W is the first dedicated study to measure the effect of biologic therapy in this patient population including spinal inflammation in patients with AS by using magnetic resonance imaging (MRI). During the study, patients were treated with 80 mg of Taltz subcutaneously either every four weeks or every two weeks (following 80 mg or 160 mg starting dose at Week 0), or placebo. At 16 weeks, 25 percent of patients treated with Taltz every four weeks, 31 percent of patients treated with Taltz every two weeks and 13% of patients treated with placebo achieved ASAS40, the primary endpoint of the study. In addition, patients treated with Taltz achieved the following response rates at 16 weeks: ASAS20: 48 percent of patients treated with Taltz every four weeks, 47 percent of patients treated with Taltz every two weeks and 25 percent of patients treated with placebo achieved ASAS20. BASDAI CFB: patients treated with Taltz every four weeks and patients treated with Taltz every two weeks experienced a statistically significant reduction in disease activity compared to placebo as measured by BASDAI (-2.2�0.2 , -2.1�0.2 and -0.9�0.2 respectively). MRI SPARCC Spine CFB: patients treated with Taltz every four weeks and patients treated with Taltz every two weeks experienced a statistically significant reduction in spinal MRI inflammation compared to placebo as measured by the CFB in MRI spine SPARCC score ( -11.0, -9.6 and -1.5, respectively).

In both COAST-V and COAST-W, the 80 mg Q2W and Q4W dosing regimens demonstrated similar safety profiles. There were no new or unexpected safety findings in the AS population, compared to the psoriasis and psoriatic arthritis populations. The COAST-V Phase III data has been published within The Lancet and

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"Ixekizumab, an interleukin-17A antagonist in the treatment of ankylosing spondylitis or radiographic axial spondyloarthritis in patients previously untreated with biological disease-modifying anti-rheumatic drugs (COAST-V): 16 week results of a phase 3 randomised, double-blind, active-controlled and placebo-ontrolled trial."-D�sir�e van der Heijde, MD ,James Cheng-Chung Wei, MD,Maxime Dougados, MD, Philip Mease, MD, et al. Published:October 22, 2018DOI:https://doi.org/10.1016/S0140-6736(18)31946-9.

"Efficacy and Safety of Ixekizumab in the Treatment of Radiographic Axial Spondyloarthritis: 16 Week Results of a Phase 3 Randomized, Double-Blind, Placebo Controlled Trial in Patients with Prior Inadequate Response or Intolerance to Tumor Necrosis Factor Inhibitors."-Atul Deodhar Denis Poddubnyy et.al., First published: 20 October 2018 https://doi.org/10.1002/art.40753.