LILLY’S IXEKIZUMAB (TALTZ®) RECEIVES EU MARKETING AUTHORISATION FOR THE TREATMENT OF AXIAL SPONDYLOARTHRITIS (axSpA)

Ixekizumab has been granted an additional indication for the treatment of patients across the full axSpA spectrum,

including Ankylosing Spondylitis (AS), also known as radiographic axSpA (r-axSpA),

and non-radiographic-axSpA (nr-axSpA).

BASINGSTOKE, 04 June, 2020 – Eli Lilly and Company announced today that the European Medicines Agency has granted marketing authorisation (MA) for Taltz^® (ixekizumab) for the treatment of adult patients with active ankylosing spondylitis (also referred to as radiographic axial spondyloarthritis (r-axSpA)) who have responded inadequately to conventional therapy and for the treatment of adult patients with active non-radiographic axial spondyloarthritis (nr-axSpA) with objective signs of inflammation as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI) who have responded inadequately to nonsteroidal anti-inflammatory drugs (NSAIDs).[i]

AxSpA is a chronic, immune-mediated inflammatory condition characterised by inflammation of the sacroiliac joints (sacroiliitis), inflammation of the spine or both resulting in chronic back pain, fatigue and significantly reduced function and quality of life.[ii]

Dr. Dale Webb, Chief Executive Officer, NASS (National Axial Spondyloarthritis Society) said:

“Although many people may not be aware of axSpA, around 1 in 200 people have the condition, twice as many as multiple sclerosis (MS). Arthritis is often thought of as something which affects older people but 95% of people with axSpA experience their first symptoms before the age of 45 and long-term pain, impaired mobility and fatigue can have a significant negative impact on the lives of patients. For patients living with a long-term condition, new treatment options are always welcome.”

“Many patients living with axSpA suffer from chronic inflammatory back pain and the associated loss of sleep and mobility for many years before being diagnosed, and we’re pleased to be able to offer a new treatment option,” said Dr Arash Tahbaz, Senior Medical Director Eli Lilly and Company, UK and Northern Europe. “This approval reflects Lilly’s continued commitment to supporting rheumatologists and people with autoimmune conditions.”

Dr Raj Sengupta Consultant Rheumatologist, Royal National Hospital for Rheumatic Diseases said: “As a Rheumatologist, I welcome the license of ixekizumab for treatment of axial spondyloarthritis patients in the UK. The clinically meaningful benefits seen in the phase three trials supports ixekizumab to be an effective new option in the treatment paradigm for these patients.”

AxSpA comprises a spectrum of disease diagnostically divided into two subsets termed r-axSpA (synonymous with the older term ankylosing spondylitis (AS)) and nr-axSpA. R-axSpA and nr-axSpA results in a similar burden of disease on health-related quality of life.[iii]

For an axSpA diagnosis, patients are required to have at least one SpA feature (inflammatory back pain, arthritis, enthesitis, uveitis, dactylitis, psoriasis, Crohn’s disease, ulcerative colitis, good response to NSAIDS, family history of SpA, HLA-B27 positive, elevated CRP) and meet one of the imaging criteria below:

• The distinguishing characteristic of nr-axSpA is inflammation of the sacroiliac joints or spine that may be detected with magnetic resonance imaging (MRI) without definitive structural damage of the sacroiliac joints visible on x-ray.
• When definitive structural damage of the sacroiliac joints is visible on x-ray the disease is classified as r-axSpA.[iv]

The European Commission marketing authorisation for ixekizumab in axSpA was based on findings from three randomised placebo-controlled trials designed to assess the efficacy and safety in both r-axSpA and nr-axSpA:

• In r-axSpA the efficacy and safety were investigated in patients who were naïve to previous treatment with biologic disease modifying anti rheumatic drugs (bDMARDs) in COAST-V and in patients who had previous inadequate response to up to two anti-tumor-necrosis factor inhibitors (TNFi) in COAST W.
• The efficacy and safety in nr-axSpA was assessed in COAST X which included patients naïve to treatment with bDMARDs.

In all three studies ixekizumab demonstrated significant reduction of the signs and symptoms of axSpA as assessed by the proportion of patients achieving the primary endpoint of ASAS 40 improvement criteria at week 16 compared to placebo:[v] [vi] [vii]

Major secondary endpoints of all studies included improvements in disease activity assessed with the Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Disease Activity (BASDAI) and improvements in health-related quality of life assessed with the 36 Item Short Form Survey Physical Component Score (SF-36 PCS) and/or ASAS health index (ASAS-HI). The impact of ixekizumab treatment on spinal inflammation was assessed with MRI in COAST V and W and the impact on sacroiliac joint inflammation was assessed in patients with nr-axSpA in COAST X. Ixekizumab treatment resulted in significant improvements in all secondary endpoints across all 3 studies. The safety profile of ixekizumab in axSpA was consistent with that in patients with active psoriatic arthritis and moderate to severe psoriasis with the most frequently reported adverse events being, upper respiratory tract infections (most frequently nasopharygitis) and injection site reactions. The majority of adverse events were mild to moderate in nature.

[i] Lilly Data on File (CHMP notification)

[ii] Deodhar A et al. Am J Manag Care 2019;25:S319-S330

[iii] López-Medina C RMD Open. 2019;5(2):e001108

[iv] Rudwaleit M, et al. Ann Rheum Dis. 2009;68:777-783

[v] Deodhar A et al. Arthritis Rheumatol 2019;71:599-611

[vi] Van der Heijde D et al. Lancet 2018;392:2441-2451

[vii] Deodhar A et al. Lancet 2020;395:53-64