daxdilimab (HZN-7734) / SBI Biotech, Amgen - LARVOL DELTA

'RF - New treatments in cutaneous lupus erythematosus: current and future perspectives". (PubMed, Actas Dermosifiliogr) - No abstract available

Journal • Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus

A focused report on IFN-1 targeted therapies for lupus erythematosus. (PubMed, Expert Opin Investig Drugs) - "Despite these challenges, anifrolumab, voclosporin, and belimumab were approved by FDA...This review summarizes the clinical trial outcomes of four upcoming medications targeting cytokine activity: Litifilimab showed a 7-point reduction in CLASI-A in its phase II trial. Daxdilimab was unsuccessful in its phase II trial...Anifrolumab binds to the IFN-I receptor, blocking the activity of all IFN-Is, and deucravacitinib reduces IFN-I by inhibiting TYK2, thereby interfering with downstream signaling. Therapies that target IFN-I represents a promising class of medications for SLE patients."

Journal • Immunology • Infectious Disease • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • TYK2

Efficacy and Safety Results from a Phase 2 Trial of Daxdilimab in Patients with Systemic Lupus Erythematosus (ACR Convergence 2024) - P2 | "The primary endpoint was the proportion of pts achieving a British Isles Lupus Assessment Group 2004 Index–based Combined Lupus Assessment (BICLA) response and an oral glucocorticoid dose ≤7.5 mg/day and ≤baseline dose (prednisone or equivalent) at W48. DAX did not show a significant difference vs PBO in the primary endpoint, driven by the high response rate in the PBO group (Furie P, et al. Arthritis Rheumatol. 2017; 69:376-86)."

Clinical • P2 data • Cardiomyopathy • Cardiovascular • Immunology • Inflammatory Arthritis • Lupus • Rheumatology • Systemic Lupus Erythematosus

A Phase 2 Proof of Concept Study to Evaluate the Efficacy and Safety of Daxdilimab in Participants With Dermatomyositis (DM) or Anti-synthetase Inflammatory Myositis (ASIM) (clinicaltrials.gov) - P2 | N=12 | Active, not recruiting | Sponsor: Amgen | Recruiting ➔ Active, not recruiting | N=96 ➔ 12 | Trial completion date: May 2027 ➔ Oct 2025 | Trial primary completion date: Oct 2026 ➔ Mar 2025

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Dermatomyositis • Immunology • Myositis

RECAST DLE: Study of Daxdilimab (HZN-7734) in Patients With Moderate-to-Severe Primary Discoid Lupus Erythematosus (clinicaltrials.gov) - P2 | N=72 | Active, not recruiting | Sponsor: Amgen | Recruiting ➔ Active, not recruiting | Trial completion date: Mar 2025 ➔ Sep 2025 | Trial primary completion date: Mar 2025 ➔ Sep 2025

Enrollment closed • Trial completion date • Trial primary completion date • Discoid Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus

RECAST DLE: Study of Daxdilimab (HZN-7734) in Patients With Moderate-to-Severe Primary Discoid Lupus Erythematosus (clinicaltrials.gov) - P2 | N=99 | Recruiting | Sponsor: Amgen | Trial completion date: Dec 2024 ➔ Mar 2025 | Trial primary completion date: Jul 2024 ➔ Mar 2025

Trial completion date • Trial primary completion date • Discoid Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus

Study of Daxdilimab (HZN-7734) in Participants With Active Proliferative Lupus Nephritis (LN) (clinicaltrials.gov) - P2 | N=19 | Terminated | Sponsor: Horizon Therapeutics Ireland DAC | Trial completion date: Nov 2026 ➔ Jan 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Sep 2025 ➔ Jan 2024; Sponsor Decision

Trial completion date • Trial primary completion date • Trial termination • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology

HZNP-DAX-201: Study of DAXDILIMAB for the Treatment of Moderate-to-Severe Alopecia Areata (clinicaltrials.gov) - P2 | N=30 | Completed | Sponsor: Amgen | Active, not recruiting ➔ Completed

Trial completion • Alopecia • Dermatology • Immunology

Study of Daxdilimab (HZN-7734) in Participants With Active Proliferative Lupus Nephritis (LN) (clinicaltrials.gov) - P2 | N=19 | Active, not recruiting | Sponsor: Horizon Therapeutics Ireland DAC

Trial completion date • Trial primary completion date • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology

RECAST SLE OLE: Study of Daxdilimab (HZN-7734) for the Treatment of Systemic Lupus Erythematosus in an Open-label Extension Study (clinicaltrials.gov) - P2 | N=155 | Terminated | Sponsor: Horizon Therapeutics Ireland DAC | Trial completion date: Jul 2024 ➔ Oct 2023 | Active, not recruiting ➔ Terminated | Trial primary completion date: May 2024 ➔ Oct 2023; Sponsor Decision

Trial completion date • Trial primary completion date • Trial termination • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

HZNP-DAX-201: Study of DAXDILIMAB for the Treatment of Moderate-to-Severe Alopecia Areata (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: Horizon Therapeutics Ireland DAC | Phase classification: P2a ➔ P2

Phase classification • Alopecia • Immunology

Study of Daxdilimab (HZN-7734) in Participants With Active Proliferative Lupus Nephritis (LN) (clinicaltrials.gov) - P2 | N=19 | Active, not recruiting | Sponsor: Horizon Therapeutics Ireland DAC | Recruiting ➔ Active, not recruiting | N=210 ➔ 19

Enrollment change • Enrollment closed • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology

Emerging immunotherapeutic strategies for cutaneous lupus erythematosus: an overview of recent phase 2 and 3 clinical trials. (PubMed, Expert Opin Emerg Drugs) - "While the recent literature has few trials for CLE, drugs targeting type I interferon, its downstream signaling and plasmacytoid dendritic cells have shown promising results. Further research is required to develop long-awaited effective therapies, and this review highlights the importance of implementing trials dedicated to CLE to fill the current gap in CLE therapeutics."

Journal • P2 data • Review • Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

RECAST SLE OLE: Study of Daxdilimab (HZN-7734) for the Treatment of Systemic Lupus Erythematosus in an Open-label Extension Study (clinicaltrials.gov) - P2 | N=155 | Active, not recruiting | Sponsor: Horizon Therapeutics Ireland DAC | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Study Design and Rationale for the Efficacy and Safety Assessment of Daxdilimab, a Selective Plasmacytoid Dendritic Cell Depleter, in a Phase 2 Trial of Patients with Moderate-to-Severe Primary Discoid Lupus Erythematosus (EADV 2023) - P2 | "There is a significant unmet need for novel, fast-acting, and safe new therapies to reduce disease activity and damage and improve the quality of life for patients living with DLE. This is a proof-of-concept study that aims to evaluate a potentially new therapy in subjects with DLE. Figure."

Clinical • P2 data • Discoid Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus

RECAST DLE: Study of Daxdilimab (HZN-7734) in Patients With Moderate-to-Severe Primary Discoid Lupus Erythematosus (clinicaltrials.gov) - P2 | N=99 | Recruiting | Sponsor: Horizon Therapeutics Ireland DAC

New P2 trial • Discoid Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus

RECAST SLE: Study of VIB7734 for the Treatment of Moderate to Severely Active SLE (clinicaltrials.gov) - P2 | N=214 | Completed | Sponsor: Viela Bio (acquired by Horizon Therapeutics) | Active, not recruiting ➔ Completed

Trial completion • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

Horizon Therapeutics plc Announces Phase 2 Trial Evaluating Daxdilimab for the Treatment of Systemic Lupus Erythematosus (SLE) Did Not Meet Primary Endpoint (Horizon Pharma Press Release) - P2 | N=214 | RECAST SLE (NCT04925934) | Sponsor: Viela Bio (acquired by Horizon Therapeutics) | "Horizon Therapeutics plc...today announced that its Phase 2 clinical trial evaluating daxdilimab for the treatment of SLE did not show a statistically significant separation between daxdilimab and placebo on the primary endpoint, which was the proportion of patients to achieve a British Isles Lupus Assessment Group (BILAG) 2004 Index-based Combined Lupus Assessment (BICLA) response and an oral glucocorticoid (OGC) dose of ≤7.5 mg/day (prednisone equivalent), which represented a reduction from the Baseline OGC dose at 48 weeks. BICLA is a composite measure indicating low SLE disease activity. Numerical differences were seen in other endpoints. No safety concerns were reported."

P2 data • Immunology • Lupus • Systemic Lupus Erythematosus

A Phase 2 Proof of Concept Study to Evaluate the Efficacy and Safety of Daxdilimab in Participants With Dermatomyositis (DM) or Anti-synthetase Inflammatory Myositis (ASIM) (clinicaltrials.gov) - P2 | N=96 | Recruiting | Sponsor: Horizon Therapeutics Ireland DAC | Trial completion date: Jan 2026 ➔ May 2027 | Initiation date: Apr 2023 ➔ Oct 2023 | Trial primary completion date: May 2025 ➔ Oct 2026

Trial completion date • Trial initiation date • Trial primary completion date • Dermatomyositis • Immunology • Myositis

Immunohistological pattern-stratification opens the door for reliabletargeted treatment strategies in cutaneous lupus erythematosus (ISID 2023) - "This IHC-screening algorithm identified 92% (n=109) patients who expressed atleast one on these IHC-markers. 28% expressed all 3 markers at the same time, 17% MxA& CD20, 5% CD123 & CD20, 9% CD123 & MxA, 18% MxA, 7% CD20 and 9% CD123. This study demonstrates that > 90% of CLE patients might be prone to betreated with at least one targeted drug, which were developed for the treatment of SLE oris in clinical studies for CLE. These drugs include belimumab (anti-Blys/ B cells) andanifrolumab (anti-IFNabR), which have already been approved for the treatment of SLEby FDA and EMA, but also anti-pDCs drugs (BIIB059 (anti-BDCA2); Daxdilimab (AntiILT7)) and inhibitors of the JAK/STAT pathway (Tofacitinib (JAK), Lanraplenib &Filgotinib (JAK/SYK), Deucravacitinib (TYK2), which block IFN-mediatedinflammatory pathways."

Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus • CD123 • CD20 • IFNAR2 • SYK • TYK2

Horizon Therapeutics plc Announces First Patient Enrolled in Phase 2 Trial Evaluating Daxdilimab for the Treatment of Lupus Nephritis (Businesswire) - "Horizon Therapeutics plc...announced the first patient has enrolled in a Phase 2 randomized placebo-controlled trial to evaluate its development-stage medicine daxdilimab, a potentially first-in-class, fully human monoclonal antibody targeting immunoglobulin-like transcript 7 (ILT7) that depletes certain dendritic cells, to treat people with active proliferative lupus nephritis (LN)....Approximately 210 participants who meet trial eligibility are expected to be enrolled. "

Trial status • Immunology • Inflammation • Lupus • Lupus Nephritis

Session VI Treatment of CLE: Update on clinical trials for cutaneous lupus erythematosus (ISID 2023) - "Anifrolumab and belimumab have both been approved for the treatment of SLE inrecent years, and clinical trial evidence suggests some forms of CLE may improve withthese agents. Promising new therapies in development that are being evaluated withCLE-specific outcome measures include litifilimab and daxdilimab, which targetplasmacytoid dendritic cells (pDCs), iberdomide, a cereblon modulator, anddeucravacitinib, a TYK2 inhibitor. These novel therapies all have demonstrated clinicalbenefit in some forms of CLE in phase 1-2 trials. Other therapies which targetmolecules believed to play a role in CLE pathogenesis, such as janus kinases (JAKs),spleen tyrosine kinase (SYK), interferon γ (IFNγ), IL-12, and IL-23, have beenevaluated in lupus clinical trials with skin-specific outcomes but failed to meet theirprimary endpoints."

Clinical • Cutaneous Lupus Erythematosus • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • CRBN • IFNG • IL12A • IL23A • SYK • TYK2

Study of Daxdilimab (HZN-7734) in Participants With Active Proliferative Lupus Nephritis (LN) (clinicaltrials.gov) - P2 | N=210 | Recruiting | Sponsor: Horizon Therapeutics Ireland DAC | Trial primary completion date: Nov 2026 ➔ Sep 2025

Trial primary completion date • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology

A Phase 2 Proof of Concept Study to Evaluate the Efficacy and Safety of Daxdilimab in Participants With Dermatomyositis (DM) or Anti-synthetase Inflammatory Myositis (ASIM) (clinicaltrials.gov) - P2 | N=96 | Recruiting | Sponsor: Horizon Therapeutics Ireland DAC | Not yet recruiting ➔ Recruiting

Enrollment open • Dermatomyositis • Immunology • Myositis

HZNP-DAX-201: Study of DAXDILIMAB for the Treatment of Moderate-to-Severe Alopecia Areata (clinicaltrials.gov) - P2a | N=30 | Active, not recruiting | Sponsor: Horizon Therapeutics Ireland DAC | Recruiting ➔ Active, not recruiting

Enrollment closed • Alopecia