OP0195 EFFICACY AND SAFETY OF SONELOKIMAB, A NOVEL IL-17A- AND IL-17F-INHIBITING NANOBODY®, IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS (PsA): RESULTS FROM THE GLOBAL, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 2 ARGO TRIAL (2024)

Abstract

Background: Nanobodies represent a new generation of antibody-derived targeted therapies; their small size and pharmacodynamics confer a potential pharmacologic advantage to directly target sites of inflammation, which may be enhanced through the inclusion of an albumin-binding domain. Sonelokimab is a ~40 kDa novel humanized Nanobody that selectively binds with high affinity to IL-17A and IL-17F, which are central drivers of psoriatic disease, and also contains an albumin-binding domain.

Objectives: Describe the Week (W) 12 primary outcome results of the Phase 2 ARGO trial assessing the efficacy and safety of sonelokimab in patients with active PsA.

Methods: ARGO is a 24-week global, randomized, prospective, parallel-group, double-blind, placebo-controlled Phase 2 trial (NCT05640245). Eligible patients were ≥18 years old with active PsA (68-tender joint count ≥3, 66-swollen joint count ≥3), and had active psoriasis and/or a dermatologist-confirmed diagnosis of psoriasis. Patients were randomized (1:1:1:1:1) to sonelokimab 120 mg Q4W (with induction), sonelokimab 60 mg Q4W (with induction), sonelokimab 60 mg Q4W (no induction [NI]), placebo, or adalimumab (ADA) 40 mg Q2W (reference arm, not powered for statistical comparison); induction was Q2W until W8, and randomization was stratified by sex and prior biologic use. Primary endpoint was the American College of Rheumatology (ACR) 50 response at W12. Key secondary endpoints were ACR 20 and Psoriasis Area and Severity Index (PASI) 90; other endpoints included ACR 70, PASI 100, and achievement of minimal disease activity (MDA). The primary analysis was intention-to-treat (PASI outcomes were examined in patients with ≥3% BSA at baseline; 69%), with missing data imputed as non-responders.

Results: 207 patients were randomized (sonelokimab 120 mg, n=43; sonelokimab 60 mg, n=41; sonelokimab 60 mg NI, n=41; placebo, n=40; ADA, n=42). The discontinuation rate was <4% overall. Baseline characteristics were well balanced between arms (49% female, mean age 49 years, mean BMI 29.0 kg/m², mean duration of PsA 5.4 years, and 17% had prior biologic use). Primary and all key secondary endpoints were met. A significantly greater proportion of patients treated with either sonelokimab 120 mg or 60 mg achieved ACR 50 vs. placebo at W12 (sonelokimab 120 mg, 46.5%, P=0.009; sonelokimab 60 mg, 46.3%, P=0.012; sonelokimab 60 mg NI, 36.6%, P=0.086; placebo, 20.0%; Figure 1A). Key secondary outcomes also supported a positive impact of sonelokimab (ACR 20: sonelokimab 120 mg, 72.1%, P=0.002; sonelokimab 60 mg, 78.0%, P<0.001; sonelokimab 60 mg NI, 75.6%, nominal P<0.001; placebo, 37.5% [Figure 1B]; PASI 90: sonelokimab 120 mg, 59.3%, P=0.003; sonelokimab 60 mg, 76.9%, P<0.001; sonelokimab 60 mg NI, 50.0%, nominal P=0.009; placebo, 15.4%; [Figure 1C]). Significant clinical responses across domains were observed by W4. Additionally, by W12, >40% of patients in the sonelokimab 60 mg arm achieved MDA composite (43.9%, nominal P=0.022; placebo, 20.0%; Figure 2A), >30% in the sonelokimab 120 and 60 mg arms achieved a composite of both ACR 50 and PASI 100 (Figure 2B), and >25% in the sonelokimab 60 mg arm achieved a composite of both ACR 70 and PASI 100 (Figure 2C). Achievement of higher treatment response thresholds was reflected by improvements in patient QOL, including Psoriatic Arthritis Impact of Disease (PsAID)-12 (Figure 2D). Sonelokimab was well tolerated with no unexpected safety findings; there were no cases of IBD or MACE and two (1.6%) mild or moderate cases of oral candidiasis.

Conclusion: The 12-week ARGO Phase 2 trial dataset suggests that the IL-17A- and IL-17F-inhibiting Nanobody sonelokimab delivers rapid onset and robust levels of clinical response, including high-threshold outcomes, compared with placebo in patients with active PsA, with a favorable benefit–risk profile. These data support further exploration of the role for Nanobody-mediated inhibition of pivotal cytokine pathways in PsA.

Acknowledgements: NIL.

Disclosure of Interests: Iain B. Mc Innes Speakers bureau: Abbvie, UCB, Consulting fees received from: Abbvie, Amgen, AstraZeneca, BMS, Causeway Therapeutics, Cabaletta, Compugen, Eli Lilly, Evelo, Gilead, Janssen, Novartis, MoonLake Immunotherapeutics, Pfizer, Sanofi Regeneron, UCB Pharma, Grants/research support from: GSK, AstraZeneca, BMS, Eli Lilly, Janssen, Novartis, UCB Pharma, Laura C. Coates Speakers bureau: has been paid as a speaker for AbbVie, Amgen, Biogen, Celgene, Eli Lilly, Galapagos, Gilead, GSK, Janssen, Medac, Novartis, Pfizer and UCB, Worked as a paid consultant for AbbVie, Amgen, Bristol Myers Squibb, Celgene, Eli Lilly, Gilead, Galapagos, Janssen, MoonLake Immunotherapeutics, Novartis, Pfizer and UCB, Has received grants/research support from AbbVie, Amgen, Celgene, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Philip J. Mease Speakers bureau: Abbvie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer and UCB, Consultant for: Abbvie, Acelyrin, Alcaris, Alumis, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Inmagene, Janssen, MoonLake Immunotherapeutics, Novartis, Pfizer, Takeda, UCB and Ventyx, Grant/research support: Abbvie, Acelyrin, Amgen, Bristol Myers Squibb, Eli Lilly, Genascence, Janssen, Novartis, Pfizer, UCB, Alexis Ogdie Consultant for: AbbVie, Inc., Amgen, Inc., Bristol-Myers Squibb, Celgene Corporation, CorEvitas, Gilead, Janssen, Kopa/Twill Health, Lilly, Novartis Pharmaceuticals, Pfizer, UCB, and Takeda, Grant/research support: Abbvie (to Penn), Novartis Pharmaceuticals (to Penn), Pfizer, Inc (to Penn), Amgen (to Forward/NDB), NIH/NIAMS, National Psoriasis Foundation, Rheumatology Research Foundation, Forward Databank, Arthur Kavanaugh Consultant for: MoonLake Immunotherapeutics, Novartis, UCB, Pfizer, Amgen, Eli Lilly, AbbVie, Lihi Eder Speakers bureau: Abbvie, Advisory board/consultant: Abbvie, Janssen, Eli Lilly, Novartis, Pfizer, BMS, Educational/research grant: Abbvie, Eli Lilly, Pfizer, Novartis, UCB, Amgen, Fresenius Kabi, Georg Schett: None declared, Alan Kivitz Speakers bureau: AbbVie, Amgen, Flexion, GSK, Lilly, Sanofi-Regeneron, Shareholder of: Pfizer, GSK, Gilead, Novartis, Amgen, Consultant for: AbbVie, Coval, Ecor1, Fresenius Kabi, Gilead, Grunenthal, GSK, Horizon, Janssen, Prime, Prometheus, Selecta, Synact, Takeda-Nimbus, UCB, XBiotech, Nuala Brennan Shareholder in MoonLake Immunotherapeutics, Employee of MoonLake Immunotherapeutics, Alex Godwood May be a stockholder of MoonLake Immunotherapeutics, Employee of MoonLake Immunotherapeutics, Eva Cullen Speakers bureau: has presented at congresses as part of current employment with MoonLake Immunotherapeutics, May be a stockholder of MoonLake Immunotherapeutics, Employee of MoonLake Immunotherapeutics, Kristian Reich Professor Reich has served as advisor and/or paid speaker for and/or participated in clinical trials sponsored by Abbvie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Galderma, Janssen-Cilag, Kyowa Kirin, LEO Pharma, Lilly, Medac, Novartis, Ocean Pharma, Pfizer, Sanofi, UCB, Professor Reich is a shareholder of MoonLake Immunotherapeutics, Professor Reich is an employee of MoonLake Immunotherapeutics, Christopher T. Ritchlin Consultant for: Abbvie, UCB, MoonLake Immunotherapeutics, BMS, Novartis, Janssen, Solarea, Lilly, Joseph F. Merola Consultant and/or investigator for: Amgen, Astra-Zeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Abbvie, Dermavant, Eli Lilly, Incyte, MoonLake Immunotherapeutics, Novartis, Janssen, UCB, Sanofi-Regeneron, Sun Pharma, Biogen, Pfizer and Leo Pharma, Consultant and/or investigator for: Amgen, Astra-Zeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Abbvie, Dermavant, Eli Lilly, Incyte, MoonLake Immunotherapeutics, Novartis, Janssen, UCB, Sanofi-Regeneron, Sun Pharma, Biogen, Pfizer and Leo Pharma.