HS Pipeline Update: HS Patients Taking Nanobody Sonelokimab Hit HiSCR 75 as Early as Week 12
This is the first placebo-controlled randomized trial in HS to report positive topline results using HiSCR75 as the primary endpoint, according to MoonLake Immunotherapeutics.
Nanobody Sonelokimab is looking good in patients with moderate-to-severe hidradenitis suppurativa (HS), according to topline Phase 2 results from MoonLake Immunotherapeutics.
Nanobodies are 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). MoonLake Immunotherapeutics' Sonelokimab 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 not yet approved for use in any indication.
The MIRA trial (M1095-HS-201), which recruited 234 patients, is the first randomized, double-blind, placebo-controlled trial to use Hidradenitis Suppurativa Clinical Response (HiSCR) 75 as its primary endpoint, a higher measure of clinical response versus the HiSCR50 measure used in other clinical trials.
The trial met its primary endpoint with a significantly greater proportion of patients treated with both sonelokimab 120mg and 240mg achieving HiSCR75 compared to those on placebo at week 12. The primary analysis was based on the most stringent type of analysis for such trials, intent-to-treat non-responder imputation (ITT-NRI). Both doses performed similarly, with the 120mg dose providing the highest delta on HiSCR75 and HiSCR50. The 120mg dose achieved a 29 ppt delta to placebo on HiSCR75 and a 38ppt delta to placebo on HiSCR50 (p<0.0001). The results suggest that, as early as week 12, the Nanobody sonelokimab, relative to placebo, reaches the highest clinical activity among all other therapies tested in similarly stringent pivotal-like trials.
In addition, other clinically relevant secondary endpoints, such as HiSCR90, improvements in International Hidradenitis Suppurativa Severity Score System (IHS) 4, abscess/nodule and draining tunnel counts as well as patient reported pain and quality of life outcomes also reached statistical significance at week 12. The high performance of the Nanobody at 120mg, the dose found to be optimal in psoriasis, demonstrates the advantage of using a smaller biologic with albumin-binding capacity to inhibit IL-17A and IL-17F for the treatment of inflammatory diseases.
The safety profile of sonelokimab was consistent with previously reported studies with no new safety signals observed. Overall, sonelokimab continues to show a favorable safety profile, in line with the known profile of IL-17 inhibitors.
“Hidradenitis suppurativa is a chronic, inflammatory, recurrent, and debilitating skin disease that has profound and wide-ranging impacts across many aspects of patient’s lives,” says Alexa B. Kimball, MD, MPH, lead investigator of the MIRA trial, investigator at Beth Israel Deaconess Medical Center, Massachusetts, US, and Professor of Dermatology at Harvard Medical School, in a news release. “As a physician, I see tremendous need for new treatment options for people living with HS, particularly for treatments to reach high thresholds of response in clinical trials (e.g., HiSCR75 and beyond). The positive high clinical responses observed with sonelokimab in the Phase 2 MIRA trial are encouraging, demonstrating its promise as a potential future treatment option.”
Jorge Santos da Silva, PhD, Founder and Chief Executive Officer at MoonLake, adds: “As part of our efforts to elevate outcomes for patients, we set an ambitious goal for our Nanobody sonelokimab to ‘meet or beat’ the best results shown in pivotal-like trials of competitors. We have achieved our ‘beat’ goal with the positive outcome of the Phase 2 MIRA trial. In doing so, we have raised the bar for what can be accomplished for HS and these positive topline data provide us with even greater confidence as we look forward to our next steps and our aspiration to become a leader in the inflammation and immunology space.”
“The positive topline results from the MIRA trial establish a new era in the treatment of chronic inflammatory diseases, as our Nanobody sonelokimab indicates a new bar versus what was achieved previously with monoclonal antibodies,” says Kristian Reich, MD, PhD, Founder and Chief Scientific Officer at MoonLake. “Importantly, the results confirm the advantage of the Nanobody’s smaller size versus traditional antibodies in the treatment of diseases in which high-level improvements depend on optimal tissue penetration such as hidradenitis suppurativa and likely psoriatic arthritis. The data also validate sonelokimab’s unique mode of action to efficiently inhibit IL-17F in addition to IL-17A. The positive outcome of the MIRA trial would not have been possible without the support and participation of the patients and investigators to whom we are grateful.”
These topline data will be discussed on Monday June 26, 2023 at 2pm CEST/8am EDT before the Nasdaq market opens, via webcast at:
A replay of the webcast and the presentation document will be made available at https://ir.moonlaketx.com.
The MIRA 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 switching to sonelokimab from the placebo and the adalimumab arms. Full results from the MIRA trial will be submitted for publication in a peer-reviewed medical journal and for presentation at an upcoming scientific meeting.
Sonelokimab has already been successfully assessed in a randomized, placebo-controlled, Phase 2b trial in 313 patients with moderate-to-severe plaque-type psoriasis in which it demonstrated a rapid and durable skin clearance (PASI100) with no unexpected safety findings.
Sonelokimab is currently being evaluated in a Phase 2 trial (‘ARGO’) in patients with active psoriatic arthritis with the primary end-point readout expected in Q4 this year.
*Nanobody and Nanobodies are trademarks of Ablynx, a Sanofi company.