Novartis’ Axial Spondyloarthritis Drug, Cosentyx Shines in Phase 3 Study
By T. Chakraborty, Ph.D.
The Annual European Congress of Rheumatology organized by the European League Against Rheumatism (EULAR) was held between June 3-6. At the virtual meeting, the encouraging Phase 3 trial results of Cosentyx were announced.
Axial Spondyloarthritis (axSpA)
Axial Spondyloarthritis is a form of long-term inflammatory arthritis that most commonly affects the spine and is characterized by chronic inflammatory back pain. AxSpA is used as the broad-spectrum term which includes Ankylosing Spondylitis (AS), where changes to the spine can be seen on X-ray, and non-radial axial spondyloarthritis (nr-axSpA), where symptoms are not visible.
Approximately 1.7 million people are diagnosed with nr-axSpA in the top five European countries and the USA, which not only presents a socioeconomic burden to the patients but also renders them debilitating pain. The number could be much higher as this condition remains unrecognized due to an average delay in diagnosis of seven years.
Cosentyx, an anti-IL-17A Monoclonal Antibody
On June 4th, Novartis, a biopharma leader with a keen focus in rheumatology and immuno-dermatology, announced promising results of their Phase 3 PREVENT trial that evaluated Cosentyx (secukinumab) across the axSpA span .
Jürgen Braun, MD, Professor of Rheumatology at Ruhr-University Bochum, Germany, who is also an investigator in the PREVENT trial, said, “Axial spondyloarthritis can have a serious impact on a patient’s quality of life and ability to carry out everyday tasks. PREVENT demonstrated the efficacy and safety of secukinumab in non-radiographic axial spondyloarthritis, showing early and sustained relief from the signs and symptoms of this often-painful disease” .
The treatments for axSpA is mainly aimed to reduce pain and stiffness in patients so that they can continue their normal activities. Existing treatments include non-steroidal anti-inflammatory drugs (NSAID), exercise, and physical therapy. Recently, targeted therapy against proteins involved in inducing axSpA like inflammatory proteins is coming to the forefront. One such inflammatory molecule in the disease etiology is IL-17A.
Genome-wide association studies (GWAS) have identified the major histocompatibility class (MHC) I region as highly associated with the development of axSpA. Various immunological functions, including IL-17A signaling, can be altered by these genetic associations. Further, multiple single nucleotide polymorphism (SNP) studies have identified SNPs on IL-17, which are associated with axSpA. Furthermore, patients have elevated levels of IL-17A in serum, making it an interesting target for the treatment [3,4].
Cosentyx is a fully-humanized monoclonal antibody against IL-17A developed by Novartis. This drug went into clinical trials for other inflammatory diseases in 2010 and first received FDA approval in 2015 to treat plaque psoriasis. Since then, this drug has been approved for the treatment of psoriatic arthritis and ankylosing spondylitis. Earlier this year, Cosentyx received approval for the treatment of nr-axSpA .
The trial started by enrolling 555 patients with active nr-axSpA who have been on two different NSAIDs for up to 4 weeks before the study. The primary endpoint was achieving the ASAS40 response, meaning that there will be at least a 40% improvement in disease symptoms. The secondary endpoint of this clinical trial included health-related quality of life, mobility, and pain. 90% of the patients enrolled were biologic-naïve. The drug was administered at a dose of 150 mg subcutaneously on a monthly basis. The drug significantly improved the disease state compared to placebo both at 16 weeks (41.5% vs. 29.2%) and at 52 weeks (35.4% vs. 19.9%). Further, at 52 weeks, secondary endpoints were also significantly improved post drug treatment. No new safety concerns or side effects were observed, suggesting that IL-17A inhibition using Cosentyx is a feasible treatment paradigm for this inflammatory form of the disease .
Multiple biopharmaceutical companies have recognized the importance of IL-17 as a target for axSpA and have developed monoclonal antibodies to target the pathways. Of notable interest is Ixekizumab from Eli Lilly. Ixekizumab (Taltz) has been shown to improve nr-axSpA in phase III COAST-X study. Brodalumab is an IL-17 inhibitor developed by Amgen, which is also under investigation. Other monoclonal antibodies like Bimekizumab and Netakimab are also under clinical trials for the treatment of axSpA .
Editor: Rajaneesh K. Gopinath, Ph.D.
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