Eli Lilly's Taltz (Ixekizumab) Receives FDA Approval for Expanded Indication in Active Ankylosing Spondylitis

Today, Eli Lilly announced that the U.S. FDA has approved an expanded indication for its new drug Taltz (ixekizumab) for the treatment of active ankylosing spondylitis (AS), also known as radiographic axial spondyloarthritis (r-axSpA). This marks the third approved indication for ixekizumab. Previously, ixekizumab was approved for the treatment of active psoriatic arthritis in adults, as well as moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.

Ankylosing spondylitis (AS) is a type of spondyloarthritis that affects the pelvic joints and spine, manifesting as chronic inflammatory back pain, spinal stiffness, and impaired skeletal function and mobility. In its most severe cases, inflammation can lead to new bone formation, causing spinal segments to fuse in a fixed, immobile position. There are approximately 4.5 million adult AS patients worldwide. Based on whether radiographic damage to the sacroiliac joints can be detected by X-ray, AS patients are classified into two categories: non-radiographic axial spondyloarthritis (nr-axSpA) and radiographic axial spondyloarthritis (r-axSpA).

The monoclonal antibody ixekizumab selectively binds to interleukin-17A (IL-17A) and inhibits its interaction with the IL-17 receptor. IL-17A is a naturally occurring cytokine involved in normal inflammatory and immune responses. By inhibiting IL-17 receptor-mediated signaling pathways, ixekizumab suppresses the release of pro-inflammatory cytokines and chemokines, thereby alleviating symptoms of inflammatory diseases.

The approval of this expanded indication is based on the positive results from two Phase 3 trials, COAST-V and COAST-W. COAST-V and COAST-W were designed to evaluate the efficacy and safety of ixekizumab in patients with ankylosing spondylitis (AS) who were naive to biologic disease-modifying antirheumatic drugs (bDMARDs), and in those who had an inadequate response or were intolerant to standard therapy with tumor necrosis factor inhibitors (TNFi), respectively.

The primary and secondary endpoints of the COAST trial were the proportion of patients achieving Assessment of SpondyloArthritis international Society 40 (ASAS40) response and the proportion achieving ASAS20 response, respectively, at Week 16. ASAS40 represents a ≥40% improvement in disease signs and symptoms, such as pain, inflammation, and function. The COAST trial was the first registrational trial to use ASAS40 as its primary endpoint and to meet this endpoint.

In the ixekizumab groups of the COAST-V and COAST-W trials, 48% and 25% of patients, respectively, achieved the primary endpoint of ASAS40, compared with 18% and 13% in the placebo groups. In the ixekizumab groups of the COAST-V and COAST-W trials, 64% and 48% of patients, respectively, achieved the secondary endpoint of ASAS20, compared with 40% and 30% in the placebo groups.

References:

[1] AstraZeneca agrees to buy US FDA Priority Review Voucher from Sobi. Retrieved Aug. 26, 2019, from https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2019/astrazeneca-agrees-to-buy-us-fda-priority-review-voucher-from-sobi-22082019.html

[2] Express | Eli Lilly's Blockbuster New Drug Approved for the Treatment of Psoriatic Arthritis. Retrieved Aug. 26, 2019, from https://mp.weixin.qq.com/s/sIbOz7RdQcWIHBFw5k7Akg

[3] Flash | Eli Lilly’s IL-17A Antagonist Shows Positive Phase 3 Results, Regulatory Submission to Be Filed This Year. Retrieved Aug. 26, 2019, from https://mp.weixin.qq.com/s/WxdoiJDx0GNjhpvv7x7pdg

Original Title: Express | Eli Lilly's IL-17 Inhibitor Approved for Expanded Indication to Treat Spondyloarthritis

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