Sonelokimab (M-1095) is currently in development to address moderate to severe plaque psoriasis, psoriatic arthritis, palmo-plantar pustulosis, ankylosing spondylitis (r-axSpA), and hidradenitis suppurativa. This drug candidate is administered via subcutaneous injection. Its mechanism of action involves inhibiting IL-17A and IL-17F, key cytokines implicated in inflammatory processes, thereby targeting the underlying immune-mediated pathways driving these conditions.

In phase II study (NCT05640245) with 207 patients randomized into different treatment groups (sonelokimab 120 mg, n=43; sonelokimab 60 mg, n=41; sonelokimab 60 mg NI, n=41; placebo, n=40; adalimumab, n=42), less than 4% of participants discontinued the trial. Baseline characteristics were similar across all groups, with 49% female participants, an average age of 49 years, an average BMI of 29.0 kg/m2, a mean PsA duration of 5.4 years, and 17% prior biologic use.

The primary and key secondary endpoints were achieved. By week 12, a significantly higher percentage of patients receiving sonelokimab 120 mg (46.5%) and 60 mg (46.3%) achieved ACR 50 compared to placebo (20.0%). The 60 mg NI group had 36.6%. For ACR 20, the results were sonelokimab 120 mg (72.1%), sonelokimab 60 mg (78.0%), sonelokimab 60 mg NI (75.6%), and placebo (37.5%). PASI 90 results were sonelokimab 120 mg (59.3%), sonelokimab 60 mg (76.9%), sonelokimab 60 mg NI (50.0%), and placebo (15.4%).

Significant clinical responses were seen as early as week 4. By week 12, over 40% of patients in the sonelokimab 60 mg group achieved the MDA composite (43.9%) compared to placebo (20.0%). More than 30% in the sonelokimab 120 mg and 60 mg groups achieved both ACR 50 and PASI 100, and over 25% in the sonelokimab 60 mg group achieved both ACR 70 and PASI 100. These improvements were also reflected in better quality-of-life measures, including PsAID-12 scores.

Sonelokimab was well tolerated with no unexpected safety issues. There were no cases of inflammatory bowel disease (IBD) or major adverse cardiovascular events (MACE), and only two mild or moderate cases of oral candidiasis (1.6%).

KOL Insight

“Exciting results from the ARGO trial! Sonelokimab, a novel IL-17A and IL-17F inhibiting nanobody, shows significant clinical response in PsA patients at Week 12. High efficacy with a favorable safety profile that needs to be verified in bigger, Phase III RCTs.”- Researchers, US

Conclusion:

MoonLake Immunotherapeutics aims to uphold its prominence as a significant contender in developing an IL-17 inhibitor for inflammatory skin conditions, as evidenced by a successful Phase II trial. The trivalent camelid nanobody, named sonelokimab, demonstrated a notable and statistically significant improvement. Acelyrin's setback with izokibep in the clinical trial for hidradenitis suppurativa contrasts with the success of sonelokimab's Phase II results, positioning sonelokimab to potentially capture a significant market share in treating this condition.

In PsA the company will face competition with bimekizumab as in EULAR UCB presented data of Phase III.  Bimekizumab treatment consistently maintained robust efficacy in PsA patients, demonstrating durable improvement in joint and skin outcomes over two years, irrespective of prior bDMARD use.

The 12-week ARGO Phase II trial data indicate that sonelokimab nanobody provides rapid and robust clinical responses in patients with active PsA compared to placebo. This includes achieving high-threshold outcomes and showcasing its potential effectiveness. The trial demonstrated a favorable benefit-risk profile for sonelokimab, with significant improvements in disease activity and quality of life measures and no unexpected safety concerns. These promising results suggest that Nanobody-mediated inhibition of pivotal cytokine pathways could be a valuable therapeutic strategy in PsA, warranting further investigation.