- First placebo-controlled randomized trial in active psoriatic arthritis (PsA) using a Nanobody® to report positive topline results in support of potential best-in-class profile
- Primary endpoint ACR50 met with up to 47% (p<0.01 versus placebo) of patients on sonelokimab achieving ACR50 as early as week 12
- All key secondary endpoints met including up to 77% (p<0.001 versus placebo) of patients on sonelokimab achieving PASI90 as early as week 12
- Other secondary endpoints also reached statistical significance at week 12, including endpoints focused on deep tissue inflammation, Minimal Disease Activity (MDA) and patient reported outcomes
- High threshold outcomes, including ACR70 and PASI100, continue to improve beyond week 12, consistent with previous studies of sonelokimab
- Discontinuation rate below 4% and safety results of sonelokimab consistent with previously reported studies with no new safety signals
- The top-line data will be discussed on Monday 6 November, at
2pm CET /8am ET , via webcast (registration link below)
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
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.
These topline data will be discussed on
https://edge.media-server.com/mmc/p/bp43a4xr
A replay of the webcast and the presentation document will be made available at https://ir.moonlaketx.com.
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.
Today’s top-line data announcement follows the announcement in
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
Sonelokimab is not yet approved for use in any indication.
- Ends -
About Psoriatic Arthritis
Psoriatic arthritis (PsA) is a chronic and progressive inflammatory arthritis associated with psoriasis primarily affecting the peripheral joints. The clinical features of PsA are diverse, involving pain, swelling, and stiffness of the joints, which can result in restricted mobility and fatigue. PsA occurs in up to 30% of patients with psoriasis, most commonly those aged between 30 and 60 years. The symptom burden of PsA can have a substantial negative impact on patient quality of life. Although the exact mechanism of disease is not fully understood, evidence suggests that activation of the IL-17 pathway plays an important role in the disease pathophysiology.
About the ARGO trial
The ARGO trial (M1095-PSA-201) is a global, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of the Nanobody® sonelokimab, administered subcutaneously, in the treatment of adult patients with active PsA. The trial is designed to evaluate different doses of sonelokimab, with placebo control and adalimumab as an active reference arm. The primary endpoint of the trial is the percentage of participants achieving ≥50% improvement in signs and symptoms of disease from baseline, compared to placebo, as measured by the
About Sonelokimab
Sonelokimab (M1095) is an investigational ~40 kDa humanized Nanobody® consisting of three VHH domains covalently linked by flexible glycine-serine spacers. With two domains, sonelokimab selectively binds with high affinity to IL-17A and IL-17F, thereby inhibiting the IL-17A/A, IL-17A/F, and IL-17F/F dimers. A third central domain binds to human albumin, facilitating further enrichment of sonelokimab at sites of inflammatory edema.
Sonelokimab is being assessed in two trials, the Phase 2 ARGO trial in PsA (trial ongoing) and the Phase 2 MIRA trial in HS. In
Sonelokimab has also been assessed in a randomized, placebo-controlled Phase 2b trial (NCT03384745) in 313 patients with moderate-to-severe plaque-type psoriasis. Clinical response (considering the Investigator’s Global Assessment Score 0 or 1, and the Psoriasis Area and Severity Index 90/100) was observed in patients with moderate-to-severe plaque-type psoriasis. Sonelokimab was generally well tolerated, with a safety profile similar to the active control, secukinumab (Papp KA, et al.
In an earlier Phase 1 trial in patients with moderate-to-severe plaque-type psoriasis, sonelokimab has been shown to decrease (to normal skin levels) the cutaneous gene expression of pro-inflammatory cytokines and chemokines (Svecova D. J Am Acad Dermatol. 2019;81:196–203).
About Nanobodies®
Nanobodies® represent a new generation of antibody-derived targeted therapies. They consist of one or more domains based on the small antigen-binding variable regions of heavy-chain-only antibodies (VHH). Nanobodies® have a number of potential advantages over traditional antibodies, including their small size, enhanced tissue penetration, resistance to temperature changes, ease of manufacturing, and their ability to be designed into multivalent therapeutic molecules with bespoke target combinations.
The terms Nanobody® and Nanobodies® are trademarks of Ablynx, a Sanofi company.
About MoonLake Immunotherapeutics
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