Sonelokimab Promising for Patients with PsA

The 24-week, phase 2 ARGO clinical trial (NCT05640245) evaluated the safety and efficacy of subcutaneous sonelokimab (M1095), an investigational humanized nanobody, in adults with active psoriatic arthritis (PsA).^1,2

Sonelokimab consists of three, heavy-chain-only domains that selectively bind with high affinity to interleukin (IL) 17A and IL-17F on two domains that inhibit IL-17A/A, IL-17A/F and IL-17F/F dimers. A third domain binds with human albumin, resulting in the delivery of sonelokimab to inflammatory sites. (Note: Nanobody and nanobodies are trademarks of Ablynx, a Sanofi company.)³

Nanobodies, of which a handful of therapeutic products are already approved, represent a new generation of antibody-derived targeted therapies.⁴ They contain one or more domains based on the small antigen-binding variable regions of heavy-chain-only antibodies. The potential advantages of nanobodies over traditional antibodies include their small size, enhanced tissue penetration, resistance to temperature changes, ease of manufacturing and their ability to be designed into multivalent therapeutic molecules with personalized target arrangements. Nanobodies can also pass the blood-brain barrier, even if the blood-brain barrier is compromised due to neurological conditions.³

The ARGO clinical trial was both double blind and placebo controlled and used adalimumab in an active reference arm. Its primary end point was the percentage of patients who achieved an ACR50 clinical response (i.e., achieving a 50% or greater improvement in the signs and symptoms of PsA from baseline), compared with placebo. Patients received either 60 mg of sonelokimab or 120 mg of sonelokimab with induction, and 207 patients participated in the trial.¹

The Results

The study met this primary end point. Patients continued to improve from week 12 and exceeded a 60% response by week 24. At week 24, approximately 40% of treated patients achieved an ACR70 response. Also at week 24, more than 80% of patients achieved a Psoriasis Area and Severity Index (PASI) 90 response and 60% achieved a PASI100. Both doses of sonelokimab led to similar results, which surpassed the results for the adalimumab arm.¹

Secondary end points included improvement in ACR20 response compared with placebo, complete skin clearance as measured by at least a PASI improvement of 100%, physical function improvement measured by the Health Assessment Questionnaire-Disability Index, enthesitis measured by the Leeds Enthesitis Index and pain improvement as measured by the Patients Assessment of Arthritis Pain. All key secondary end points were met for both doses of sonelokimab.

Sonelokimab vs. Adalimumab

Sonelokimab treatment resulted in improvements in composite scores in different domains, including joints and skin, with up to a 16 to 29 percentage point difference compared with adalimumab treatment. These composite scores included ACR50+PASI90, with up to 59% response; ACR 50+PASI100, with up to 52% response; ACR70+PASI100, with up to 48% response; and minimal disease activity, with up to 61% response.¹

The 60 mg dose of sonelokimab was adequate to reach high levels of response in the general trial population. However, the 120 mg dose of sonelokimab was found to further improve responses in specific patient subgroups. Therefore, it’s anticipated both doses will be investigated in phase 3 clinical trials.

The discontinuation rates were low (~5%), and the safety profile of sonelokimab was consistent with previous studies. No new safety signals were identified.

Michele B. Kaufman, PharmD, BCGP, is a freelance medical writer based in New York City and a pharmacist at New York Presbyterian Lower Manhattan Hospital.

References

1. MoonLake announces significant improvements with nanobody sonelokimab over 24 weeks in active psoriatic arthritis (PsA) and other important updates at its R&D Day [news release]. MoonLake Immunotherapeutics. 2024 Mar 10.
2. Evaluation of sonelokimab for the treatment of patients with active psoriatic arthritis [NCT05640245]. ClinicalTrials.gov. 2024 Apr 25.
3. Jin B-K, Odongo S, Radwanska M, et al. Nanobodies: A review of generation, diagnostics and therapeutics. Int J Mol Sci. 2023:24:5994.
4. Sanofi’s Cablivi (caplacizumab-yhdp): A new era in acquired thrombotic thrombocytopenic purpura (aTTP) treatment [news release]. Sanofi. 2019 Feb 6.