Novartis announced their plan to initiate ARROW, a head-to-head proof of concept study to assess the mechanistic superiority of the direct inhibition of IL-17A with Cosentyx (secukinumab) over the inhibition of IL-23 with Tremfya (guselkumab) in patients with psoriatic plaques resistant to treatment with Stelara.
Study results are expected in 2019.
“We know there are different immune mechanisms driving the clinical manifestations of psoriasis, including the involvement of joints, scalp, nails, palms, and soles psoriasis. Results from the ARROW trial could help us learn more about the differences between the direct targeting of IL-17A and IL-23 in psoriasis,” said Kristian Reich, M.D., Ph.D., Georg-August-University Göttingen and Dermatologikum Hamburg, Germany.
“Treating all manifestations of psoriasis in the most effective way is crucial for patients and physicians. We are proud to be driving scientific activities to elucidate the biologic pathways in these diseases with the goal of transforming treatment options for patients,” said Shreeram Aradhye, CMO and global head, Medical Affairs, Novartis Pharmaceuticals.
The ARROW study objective is to assess the mechanistic superiority of Cosentyx over Tremfya in controlling clinical activity in psoriatic plaques resistant to treatment with Stelara. IL-23 independent pathways of IL-17A release are potentially involved in inflammation of other persistent localizations, including joints, scalp, nails, palms, and soles psoriasis. Up to 90 percent of people with psoriasis may develop nail or palmoplantar psoriasis,. Nail psoriasis is an important predictor of psoriatic arthritis (PsA) which affects up to 40 percent of patients with psoriasis.
Cosentyx is the first fully-human biologic that specifically inhibits interleukin-17A (IL-17A), a cornerstone cytokine involved in the inflammation and development of psoriasis, ankylosing spondylitis (AS), and psoriatic arthritis (PsA)–. IL-17A is produced by both IL-23 dependent and IL-23 independent pathways, by various cells from both the innate immune system (which can be triggered by mechanical stress) and the adaptive immune system. By acting directly on IL-17A, Cosentyx inhibits this cornerstone cytokine irrespective of where the IL-17A comes from.
This study is now the 100th trial with Cosentyx in the last 10 years, adding to the wealth of data. Cosentyx has a broad head-to-head study program that includes FIXTURE, CLEAR, CLARITY, SURPASS and EXCEED clinical superiority trials,–. To date, Cosentyx has been prescribed to more than 150,000 patients with psoriasis, PsA, and AS worldwide.
ARROW (CAIN457A2403) is a global multicenter open label randomized proof of concept Phase 2a study designed to assess the mechanistic superiority of secukinumab 300 mg over guselkumab 100 mg in achieving the clearing of psoriatic skin plaques resistant to treatment with ustekinumab after 16 weeks. 40 patients will be randomized 1:1 to secukinumab or guselkumab and treated for 16 weeks.
The primary endpoint of the study is the percentage of patients achieving clear or almost clear status of the ustekinumab-resistant plaques as assessed through the Total Clinical Score (TCS =<2). The mechanistic exploratory endpoints of this study will explore the hypothesis that the direct targeting of IL-17A is able to overcome IL-23 independent mechanisms of resistance, providing a more complete approach to the control of alternative pathways of psoriasis inflammation.
- Expected to be available on clinicaltrials.gov imminently.
- Clinicaltrials.gov. Active trials include all those that are listed as recruiting, active but not recruiting, enrolling by invitation and not yet recruiting and completed. This list excludes all trials listed as suspended, terminated and withdrawn.
- Novartis. Data on file.
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- Bagel J et al. Secukinumab is Superior to Ustekinumab in Clearing Skin of Patients with Moderate to Severe Plaque Psoriasis: CLARITY, a Randomized, Controlled, Phase 3b Trial. Presented as poster 98 at The Winter Clinical Dermatology Conference – Hawaii. January 13, 2018.
- Effect of Secukinumab on Radiographic Progression in Ankylosing Spondylitis as compared to GP2017 (Adalimumab Biosimilar) (SURPASS). Available at: https://www.clinicaltrials.gov/ct2/show/NCT03259074. Last accessed November 2017.
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- Cosentyx Summary of Product Characteristics. Novartis Europharm Limited. Available at: https://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/003729/human_med_001832.jsp&mid=WC0b01ac058001d124. Accessed April 2018.
- Smith JA et al. Review: The Interleukin 23/Interleukin 17 Axis in Spondyloarthritis Pathogenesis: Th17 and Beyond. Arthritis Rheumatol. 2014;66:231-41.
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Filed Under: Drug Discovery