MoonLake Immunotherapeutics announced positive top-line results from its global Phase 2 ARGO trial evaluating the efficacy and safety of the Nanobody® sonelokimab in patients with active psoriatic arthritis (PsA). The ARGO trial (M1095-PSA-201), which enrolled 207 patients, met its primary endpoint with a statistically significant greater proportion of patients treated with either sonelokimab 60mg or 120mg (with induction) achieving an American College of Rheumatology (ACR) 50 response compared to those on placebo at week 12. Specifically, for the 60mg and 120mg doses with induction, respectively, 46% and 47% of patients treated with sonelokimab achieved ACR50 (p<0.01 versus placebo); 78% and 72% of patients achieved ACR20; and 29% and 26% achieved ACR70.

The primary analyses were based on the most stringent type of analysis for such trials, intention-to-treat with non-responder imputation (ITT-NRI). As expected, the 60mg dose without induction did not reach statistical significance, confirming the 60mg and 120mg with induction as the potential dose regimens to carry forward into Phase 3. All key secondary endpoints were met for the 60mg and 120mg doses with induction. The key secondary endpoint Psoriasis Area and Severity Index (PASI) 90 was met for all doses with induction; 77% of patients responding at week 12 to the 60mg dose (ITT-NRI, p<0.001 versus placebo).

For this dose, 58% of patients achieved complete skin clearance (PASI100) at week 12. PASI responses across dose arms were consistent with the previously reported Phase 2b data of sonelokimab in moderate-to-severe plaque-type psoriasis, with the 120mg dose achieving the highest responses for PASI100 (close to 60% of patients at week 12, ITT-NRI) in patients with more severe skin lesions (PASI score = 10 at baseline). Other clinically relevant secondary endpoints, such as Minimal Disease Activity (MDA), the modified Nail Psoriasis Severity Index (mNAPSI), the Leeds Enthesitis Index (LEI) and the patient self-reported Psoriatic Arthritis Impact of Disease (PsAID-12), each show promising levels of response at week 12.

Adalimumab was used as an active reference to validate responses across arms (not powered for statistical comparisons to active treatment). Sonelokimab 60mg and 120mg (with induction) numerically outperformed adalimumab on the primary endpoint and all key secondary endpoints, with the observed deltas further supporting the potential for sonelokimab as a future leading therapy. The patient discontinuation rate in the ARGO trial was low at week 12 (less than 4%), similar to what was observed in previous trials of sonelokimab in psoriasis and hidradenitis suppurativa.

The safety profile of sonelokimab in ARGO was consistent with previously reported studies with no new safety signals. Specifically, oral candidiasis was observed in less than 2% of patients on sonelokimab, with no case leading to discontinuation. No cases of inflammatory bowel disease (IBD), major adverse cardiovascular events (MACE) or suicidal ideation and behavior (SI/B) were observed.

Overall, sonelokimab continues to show a favorable safety profile. Across the sonelokimab clinical program to date, the company has not seen any signal of SI/B or liver enzyme elevations related to sonelokimab treatment. The results suggest that, as early as week 12, the Nanobody® sonelokimab reaches levels of clinical response at or above those seen with other therapies tested in similarly stringent trials.

The high performance of sonelokimab and its favorable safety profile continue to support the potential of using a smaller biologic with albumin-binding capacity to inhibit IL-17A and IL-17F for the treatment of inflammatory diseases. The ARGO trial proceeds to week 24, with a 4-week safety follow-up. Important data is being collected regarding longer-term efficacy and safety of sonelokimab, as well as results from the cross-over of patients treated with placebo or adalimumab to sonelokimab and the continued monthly dosing of sonelokimab.

top-line data announcement follows the announcement in July 2023 that the ARGO trial successfully completed randomization of its target 200 patients, several weeks ahead of schedule. Full results from the ARGO trial will be submitted for publication in a peer-reviewed medical journal and for presentation at an upcoming scientific meeting. The positive top-line12-week results from the Phase 2 ARGO trial in PsA follows the positive top-line 12-week and 24-week results from the Phase 2 MIRA trial in hidradenitis suppurativa (HS) as announced in June 2023 and October 2023.

The MIRA trial set a landmark milestone as the first placebo-controlled randomized trial in HS to report positive top-line results using HiSCR75 as the primary endpoint.