mavrilimumab (KPL-301) / Kiniksa, CSL Behring, Huadong Medicine - LARVOL DELTA

A Systematic Literature Review to Inform the 2025 EULAR Recommendations for Management of Polymyalgia Rheumatica and Large Vessel Vasculitis: Management of Disease Including Relapse and Complications (ACR Convergence 2025) - "RCTs of GCA (low RoB) reported superiority of secukinumab (Phase-2, n=1), mavrilimumab (Phase-2, n=1) and upadacitinib (Phase-3, n=1) vs placebo; Phase-2 trials of sarilumab (n=1) and sirukumab (n=1) were prematurely terminated (high RoB)...RCTs of TAK reported similar effectiveness of methotrexate or mycophenolate (unclear RoB), and superiority of adalimumab vs tocilizumab (high RoB). Phase-3 RCTs in PMR revealed superiority of tocilizumab and sarilumab (low RoB) vs. placebo while smaller phase-2 studies provided initial evidence for efficacy of rituximab (low RoB) and abatacept (unclear RoB) vs placebo (Table 1). A RCT showed similar efficacy of tofacitinib or glucocorticoids in PMR although this study was at high risk of bias. The SLR identified several new Phase-2 and Phase-3 RCTs about the efficacy and safety of IL-6i, IL-17i, Janus kinase inhibitors and B-cell depletion therapies in GCA and PMR. The SLR identified several new Phase-2 and Phase-3 RCTs about the..."

Review • Fatigue • Giant Cell Arteritis • Immunology • Musculoskeletal Pain • Pain • Rheumatology • Vasculitis

Blocking GM-CSF receptor alpha with mavrilimumab reduces production of growth factors involved in vascular remodeling in an ex-vivo model of temporal artery culture from patients with giant-cell arteritis (GCA) (ACR Convergence 2025) - "In a phase 2 clinical trial, MAV, along with a standardized prednisone taper, was superior to placebo in reducing the risk of GCA flare and increasing the rate of sustained remission at week 26(4), indicating that MAV efficiently blocks clinically-relevant inflammatory pathways in GCAPurpose: We aimed to investigate the impact of MAV on pathways involved in myofibroblast differentiation and vascular remodeling. Three patients (1 placebo, 2 MAV) consented to have a second temporal artery biopsy (TAB) at the trial completion. MAV modulates production of molecules involved in vascular remodeling in cultured arteries from patients with GCA. Whether MAV acts directly on myofibroblasts or indirectly through impairing macrophage function is being currently investigated. Further studies are ongoing to assess the functional impact of the modulated pathways on myofibroblast biology in GCA."

Preclinical • Fibrosis • Giant Cell Arteritis • Immunology • Inflammation • CSF2 • FGF2 • PDGFA • TGFB1 • XIAP

Cytokine Blockade Attenuates Inflammation and Improves Depressive Psychopathology After COVID-19: A Naturalistic Observational Study. (PubMed, J Neuroimmune Pharmacol) - "In the present naturalistic observational study we evaluated the possible effect of the cytokine-blocking agents in preventing the development of post-COVID depression in a large sample of survivors also exploring the relationship between post-COVID depressive risk, treatment with cytokine-blocking agents, and innate immune response markers. 588 COVID-19 survivors were included, of them 374 received the best available treatment at the time and 131 received standard treatment combined with cytokine-blocking agents (anakinra, tocilizumab, sarilumab, reparixin and mavrilimumab). Finally, we observed that cytokine-blocking agents' impact on depression was mediated by lowering of systemic inflammation. Our findings indicate potential efficacy of cytokine-blocking agent treatment during the early stages of COVID-19, mitigating post-COVID depressive symptoms by attenuating systemic inflammation. Further investigation through preclinical and clinical studies is..."

Journal • Observational data • CNS Disorders • Depression • Infectious Disease • Inflammation • Novel Coronavirus Disease • Psychiatry

Endothelial-Mesenchymal Transition in Tumor Microenvironment Promotes Neuroendocrine Differentiation of Prostate Cancer. (PubMed, Cancer Sci) - "Neutralization of GM-CSF signaling using mavrilimumab, a monoclonal antibody targeting the GM-CSF receptor alpha (CSF2RA), and siRNA-mediated CSF2RA knockdown both suppressed the neuroendocrine phenotype and STAT3 signaling of LNCaP cells. Enzalutamide-treated LNCaP cells secreted IL-1β and TGF-β2, which in turn triggered EndoMT, suggesting a reciprocal loop. These findings indicate that anti-androgen therapy may inadvertently promote NEPC through a paracrine loop involving tumor-derived cytokines and endothelial GM-CSF secretion, highlighting EndoMT as a microenvironmental driver of treatment resistance."

Biomarker • Journal • Castration-Resistant Prostate Cancer • Fibrosis • Genito-urinary Cancer • Immunology • Neuroendocrine Tumor • Oncology • Prostate Cancer • Solid Tumor • IL1B • TGFB1

A SYSTEMATIC LITERATURE REVIEW TO INFORM THE 2025 EULAR RECOMMENDATIONS FOR MANAGEMENT OF POLYMYALGIA RHEUMATICA AND LARGE VESSEL VASCULITIS: MANAGEMENT OF DISEASE INCLUDING RELAPSE AND COMPLICATIONS (EULAR 2025) - "RCTs of GCA (low RoB) reported superiority of secukinumab (Phase-2, n=1), mavrilimumab (Phase-2, n=1) and upadacitinib (Phase-3, n=1) vs placebo; Phase-2 trials of sarilumab (n=1) and sirukumab (n=1) were prematurely terminated (high RoB)...RCTs of TAK reported similar effectiveness of methotrexate or mycophenolate (unclear RoB), and superiority of adalimumab vs tocilizumab (high RoB). Phase-3 RCTs in PMR revealed superiority of tocilizumab and sarilumab (low RoB) vs. placebo while smaller phase-2 studies provided initial evidence for efficacy of rituximab (low RoB) and abatacept (unclear RoB) vs placebo (Table 1). A RCT showed similar efficacy of tofacitinib or glucocorticoids in PMR although this study was at high risk of bias... The systematic review identified several new Phase-2 and Phase-3 RCTs about the efficacy and safety of IL-6i, IL-17i, Janus kinase inhibitors and B-cell depletion therapies in GCA and PMR. High quality adequately sized RCTs in TAK are still..."

Review • Fatigue • Giant Cell Arteritis • Immunology • Musculoskeletal Pain • Pain • Rheumatology • Vasculitis

SYSTEMATIC REVIEW OF EFFICACY AND SAFETY OF PHARMACOLOGICAL TREATMENTS FOR GIANT CELL ARTERITIS (EULAR 2025) - P, P2, P3, P4 | "Tocilizumab (TOC; biologic, IL-6 inhibitor), upadacitinib (UPA; small molecule JAK inhibitor) and adalimumab (ADA; biologic, anti-TNF) were the only treatments reporting results from Phase 3 RCTs [8–12]...Data for the remaining 4 treatments were based on Phase 2 RCTs [mavrilimumab (MAV; biologic, GM-CSFr antagonist), secukinumab (SEC; biologic, IL-17A inhibitor), abatacept (ABA; biologic, CLTA-4Ig)] and single-arm trial [baricitinib (BAR; small molecule JAK inhibitor)] [11–16]... Based on the findings from the review there are limited treatment options available for GCA patients. TOC received regulatory approval [4], while Phase 3 results for UPA demonstrate promising efficacy and SEC is a monoclonal antibody currently in active Phase 3 development. Continued development of effective alternative glucocorticoid-sparing treatment options will support patients contraindicated or unresponsive to current treatment options and reduce the clinical burden among..."

Clinical • Review • Cardiovascular • Giant Cell Arteritis • Immunology • Infectious Disease • Inflammation • Pain • IL17A

Blocking GM-CSF receptor alpha with mavrilimumab reduces production of growth factors involved in vascular remodeling in an ex-vivo model of temporal artery culture from patients with giant-cell arteritis (GCA) (EULAR 2025) - "In a phase 2 clinical trial, MAV, along with a standardized prednisone taper, was superior to placebo in reducing the risk of GCA flare and increasing the rate of sustained remission at week 26 [4], indicating that MAV efficiently blocks clinically-relevant inflammatory pathways in GCA. MAV modulates production of molecules involved in vascular remodelling in cultured arteries from patients with GCA. Whether MAV acts directly on myofibroblasts or indirectly through impairing macrophage function needs to be elucidated. Further studies are ongoing to assess the functional impact of the modulated pathways on myofibroblast biology in GCA."

Preclinical • Fibrosis • Giant Cell Arteritis • Immunology • Inflammation • CSF2 • FGF2 • PDGFA • TGFB1 • XIAP

Corporate Update (GlobeNewswire) - "Kiniksa announced today that it is advancing KPL-1161 towards clinical development with a target profile of quarterly SC dosing...Kiniksa announced today that it plans to discontinue abiprubart development in Sjögren’s Disease. The company will explore strategic alternatives for the asset; Kiniksa announced today that it has exercised its right to terminate its exclusive license agreement for mavrilimumab with MedImmune."

Commercial • Pipeline update • Cardiovascular • Rheumatoid Arthritis • Sjogren's Syndrome

Mavrilimumab to Reduce Progression of Acute Respiratory Failure in COVID-19 Pneumonia and Systemic Hyper-inflammation (clinicaltrials.gov) - P2 | N=1 | Completed | Sponsor: Kristin Hudock | N=60 ➔ 1 | Recruiting ➔ Completed

Enrollment change • Trial completion • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Network-Based In Silico Analysis of New Combinations of Modern Drug Targets with Methotrexate for Response-Based Treatment of Rheumatoid Arthritis. (PubMed, J Pers Med) - "New game-changing drugs including Mavrilimumab, Iguratimod, Upadacitinib, Fenebrutinib, and nanoparticles may be crucial in controlling symptoms in poorly managed RA patients. Emerging therapeutic targets like Toll-like 4 receptors, NLRP3 inflammasome complexes, and mesenchymal stem cells can further transform RA therapy."

Journal • Review • Immunology • Inflammatory Arthritis • Oncology • Rheumatoid Arthritis • Rheumatology • DHFR • NLRP3 • SYK • TYMS

Giant Cell Arteritis and Polymyalgia Rheumatica: Treatment Approaches and New Targets. (PubMed, Rheum Dis Clin North Am) - "The objective of this review is to define current treatment approaches as well as new therapeutic targets and strategies. Studies investigating inhibition of cytokine pathways, including interleukin-6, interleukin-17, interleukin-23, granulocyte-macrophage colony-stimulating factor, Janus kinase-signal transduction and activator of transcription, and others, will be reviewed."

Journal • Review • Giant Cell Arteritis • Immunology • Musculoskeletal Pain • Pain • Rheumatology • IL17A • IL6

[VIRTUAL] Mavrilimumab, a human monoclonal antibody targeting GM-CSFRα, inhibits polarization to myeloid-derived suppressor cells (MDSCs) that express PD-L1 and restores T-cell proliferation in vitro. (SITC 2020) - P2 | "Ethics Approval The study was approved by the Institute of Immunology and Immunotherapy, University of Birmingham, UK Ethics Board. Healthy volunteer human material was obtained from commercial sources and approved by Stemexpress Institutional Review Board (IRB)."

IO Biomarker • Myeloid-derived suppressor cells • Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Mesothelioma • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CD14 • CD33 • CD8 • CSF2 • IL2 • ITGAM • PD-L1

[VIRTUAL] Mavrilimumab, a human monoclonal antibody targeting GM-CSFRα, inhibits polarization to myeloid-derived suppressor cells (MDSCs) that express PD-L1 and restores T-cell proliferation in vitro. (SITC 2020) - P2 | "Ethics Approval The study was approved by the Institute of Immunology and Immunotherapy, University of Birmingham, UK Ethics Board. Healthy volunteer human material was obtained from commercial sources and approved by Stemexpress Institutional Review Board (IRB)."

IO Biomarker • Myeloid-derived suppressor cells • Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Mesothelioma • Oncology • Pancreatic Adenocarcinoma • Pancreatic Cancer • Solid Tumor • CD14 • CD33 • CD8 • CSF2 • IL2 • ITGAM • PD-L1

13S112: Molecular Mechanisms of Novel Therapeutic Agents in Vasculitis (ACR Convergence 2022) - "Several new therapeutics are in clinical trials for giant cell arteritis, including anti-GM-CSF receptor, mavrilimumab, and JAK-STAT inhibitors...New therapeutics for IgG4 vasculitis will also be discussed.. Learning Objectives: Define the anti-inflammatory molecular mechanisms of anti-GM-CSF receptor in giant cell arteritis Review the new findings of a tissue resident T cell population driving smoldering large vessel vasculitis amendable to JAK-STAT inhibition Discuss the molecular mechanism of several therapeutic agents in IgG4 clinical trials"

Cognitive Disorders • Giant Cell Arteritis • Immunology • Inflammation • Vasculitis

Recent advances in the diagnosis and therapy of large vessel vasculitis. (PubMed, Pol Arch Intern Med) - "On the other hand, tocilizumab may be used to treat both diseases. Promising targeted therapies evaluated in ongoing clinical trials include, for example, anti-IL-12/23 (ustekinumab), anti-IL-17 (secukinumab), anti-IL-1 (anakinra), anti-IL-23 (guselkumab), anti-cytotoxic T-lymphocyte antigen 4 (abatacept), Janus kinase inhibitors (tofacitinib and upadacitinib), anti-granulocyte / macrophage colony-stimulating factor (mavrilimumab), and endothelin receptor (bosentan) therapies."

Journal • Cardiovascular • Giant Cell Arteritis • Immunology • Inflammation • Oncology • Rheumatoid Arthritis • Rheumatology • Vasculitis • IL12A • IL17A • IL23A

TRANSCRIPTOMIC CHANGES INDUCED BY MAVRILIMUMAB VERSUS TOCILIZUMAB IN EX-VIVO CULTURED ARTERIES FROM PATIENTS WITH GIANT-CELL ARTERITIS (EULAR 2022) - "Of 11 GCA donors, 2 had received no treatment prior to biopsy, 2 had received a single prednisone (60 mg) dose, 1 had received 2 daily doses, and the remaining 6 had extended treatment; in prednisone-treated patients, mean (SEM) treatment duration was 17.9 ±8.7 days. Mavrilimumab and tocilizumab have a different transcriptomic impact on cultured arteries from patients with GCA, with some overlapping effects, although differential effects may have been attenuated by prior GC use. A better understanding of the impact of targeted therapies on vascular inflammation is needed to improve treatment options for patients with GCA."

Preclinical • Giant Cell Arteritis • Immunology • Inflammation • BCL6 • CSF2 • CXCL1 • CXCL8 • GNAS • IL2 • IL6 • MRC1

Proinflammatory monocytes and macrophages in synovial fluid and bursal tissue of patients with polymyalgia rheumatica: potent producers of IL-6 and GM-CSF (EULAR 2022) - "Although treatment with anti-IL-6 receptor (tocilizumab) has shown promising results 2 , it is unclear whether macrophages contribute to IL-6 production in PMR. Additionally, anti-GM-CSF receptor therapy (mavrilimumab), recently shown to be efficacious in the closely related disease giant cell arteritis 3 , may also be useful for the treatment of PMR... SF monocytes and bursal tissue macrophages show a pro-inflammatory phenotype in PMR. Moreover, tissue-infiltrating macrophages show a prominent IL-6 and GM-CSF response in PMR. Our data add to the rationale of targeting IL-6 and GM-CSF as treatment options in PMR."

Clinical • Giant Cell Arteritis • Immune Modulation • Immunology • Musculoskeletal Pain • Pain • Rheumatology • CD14 • CD68 • CD86 • CSF2 • IL6 • MRC1

"mavrilimumab" (@philipcrobinson)

"Future therapeutic options in trial for #GCA include 🔺 Mavrilimumab (targeting GM-CSF) 🔺 Secukinumab (targeting IL-17A) 🔺 JAKi #BSR22" (@chriswincup)

CSF2 • IL17A

Treatment of Giant Cell Arteritis (GCA). (PubMed, J Clin Med) - "Methotrexate was considered an alternative option, but its clinical impact was limited...The approval of tocilizumab, an anti-interleukin 6 (IL-6) receptor inhibitor brought significant improvement...Interestingly, mavrilimumab, ustekinumab and, to a lesser extent, abatacept have shown promising results in phase 2 randomised controlled trials. Despite this recent progress, the value, specific condition and optimal application of each treatment remain undecided. In this review, we discuss the scientific rationale for each treatment and the therapeutic strategy."

Journal • Review • Giant Cell Arteritis • Immunology • Vasculitis • IL12A • IL17A • IL6

Advances in the Treatment of Giant Cell Arteritis. (PubMed, J Clin Med) - "MTX is the only DMARD that has shown to reduce the cumulative dose of GC, while tocilizumab is the first biologic agent approved due to its ability to decrease the relapse rate and lower the cumulative GC doses. However, apart from the IL-6 pathway, there are other pro-inflammatory cytokines and growth factors involved in the typical intima hyperplasia and vascular remodeling of GCA. Among them, the more promising targets in GCA treatment are the IL12/IL23 axis antagonists, IL17 inhibitors, modulators of T lymphocytes, and inhibitors of either the JAK/STAT pathway, the granulocyte-macrophage colony-stimulating factor, or the endothelin, all of which are updated in this review."

Journal • Review • Giant Cell Arteritis • Immunology • Vasculitis • IL12A • IL17A • IL6

Efficacy and Safety of Mavrilimumab in Giant Cell Arteritis (RheumNow) - P2 | N=42| "A phase II trial in patients with active giant cell arteritis shows that mavrilimumab, a monoclonal antibody against granulocyte-macrophage colony-stimulating factor [GM-CSF]) is capable of inducing clinical remission....MAV is an effective adjunct to steroid therapy in GCA; further study is warranted."

P2 data

Efficacy and safety of mavrilimumab in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial. (PubMed, Ann Rheum Dis) - P2 | "Mavrilimumab plus 26 weeks of prednisone was superior to placebo plus 26 weeks of prednisone for time to flare by week 26 and sustained remission in patients with giant cell arteritis. Longer treatment is needed to determine response durability and quantify the glucocorticoid-sparing potential of mavrilimumab."

Journal • P2 data • Giant Cell Arteritis • Immunology • Inflammation • Vasculitis • CSF2

Study of Mavrilimumab (KPL-301) in Participants Hospitalized With Severe Corona Virus Disease 2019 (COVID-19) Pneumonia and Hyper-inflammation (clinicaltrials.gov) - P2/3 | N=815 | Completed | Sponsor: Kiniksa Pharmaceuticals, Ltd. | Active, not recruiting ➔ Completed

Trial completion • Immunology • Infectious Disease • Inflammation • Novel Coronavirus Disease • Pneumonia • Respiratory Diseases

Mavrilimumab: Patent expiry related to composition-of-matter in 2027 (Kiniksa) - Annual Report 2021

Patent • Immunology