Rezurock (belumosudil) / Meiji Seika, Nano Terra, Romeck Pharma, BioNova Pharma, Sanofi - LARVOL DELTA

ROCK 2 inhibition with belumosudil for the treatment of chronic graft-versus-host disease: a narrative review. (PubMed, Ther Adv Hematol) - "Clinical trials demonstrated rapid and sustained overall response with belumosudil, and a favorable adverse effects profile with a low risk of infection and cytopenia in pretreated and multiorgan involved cGVHD patients, resulting in its approval for use in cGVHD. This narrative review provides an overview of the pathophysiology of cGVHD and the limitations of current treatment, and describes the pharmacologic activity, clinical studies, and real-world data supporting belumosudil use in patients with cGVHD."

Journal • Review • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Fibrosis • Graft versus Host Disease • Hematological Disorders • Immunology • Infectious Disease • Transplantation

Approved and emerging therapies for glucocorticoid-refractory chronic graft-versus-host disease. (PubMed, Curr Opin Immunol) - "In recent years, the Food and Drug Administration (FDA) has approved four agents - ibrutinib, ruxolitinib, belumosudil, and axatilimab - each targeting distinct immune and fibrotic pathways. Greater incorporation of patient-reported outcomes and long-term functional assessments into clinical trials and practice is urgently needed. Collectively, this review offers a roadmap for optimizing glucocorticoid-refractory cGVHD management, and evolving strategies hold promise for transforming glucocorticoid-refractory cGVHD from a life-limiting condition into a manageable chronic disease."

Journal • Review • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Fibrosis • Graft versus Host Disease • Immunology • Oncology • Transplantation

New molecules in the therapy of chronic graft-versus-host disease. (PubMed, Curr Opin Hematol) - "Expanding therapeutic options in cGvHD require decision-making based on organ involvement, prior therapy, and tolerability. Emerging compounds offer the potential to modulate chronic inflammation and fibrosis more precisely, supporting a move toward personalized and combinatorial approaches in advanced-line settings."

Journal • Chronic Graft versus Host Disease • Fibrosis • Graft versus Host Disease • Immunology • Inflammation • Transplantation

FDA-approved Therapies for Chronic GVHD (ICBMT 2025) - "Chronic graft-versus-host disease (cGVHD) arises in 30-50% of all patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) receiving non-manipulated donor grafts and standard calcineurin/antimetabolite GVHD prophylaxis, with randomized trials showing a lower incidence in patients receiving post-transplant cyclophosphamide or ATG. While little progress was made for several decades, in the last ten years the drugs ibrutinib, ruxolitinib, belumosudil and axatilimab were FDA-approved for cGVHD. Here we discuss which signaling pathways and cell types are targeted, the clinical studies that were the basis for FDA-approval, and future directions for clinical research."

Chronic Graft versus Host Disease • Fibrosis • Graft versus Host Disease • Immunology

Pathophysiology and Management of Chronic GVHD (ICBMT 2025) - "First-line therapy involves corticosteroids (prednisone 0.5-1 mg/kg/day) ± calcineurin inhibitors, achieving response in ~50% of patients. Steroid-refractory cGVHD, occurring in >50% of cases, is effectively managed with ruxolitinib (category 1, REACH3 trial: 49.7% response rate), ibrutinib, belumosudil, or axatilimab...Multidisciplinary care and patient-reported outcomes enhance quality of life. Ongoing trials and personalized approaches are essential to optimize efficacy, reduce toxicity, and address unmet needs in this complex post-HSCT complication."

Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • Infectious Disease • CSF2 • IFNG • TNFA

Belumosudil for Severe cGVHD: Insights from a Real-World Observational Study (ICBMT 2025) - "The median number of prior treatment lines was 4, and 15 (75%) had previously received ruxolitinib. In real-world practice, belumosudil showed favorable efficacy and safety profiles in cGVHD patients with a history of severe disease and multi-organ involvement. Key words: Belumosudil; ROCK2 inhibitor; Chronic graft-versus-host disease; Allogeneic hematopoietic stem cell transplantation; Real-world evidence"

Clinical • Observational data • Real-world • Real-world evidence • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease

Molecular Profiling of Belumosudil-Treated IOMM-Lee Meningioma Cells Reveals Repurposing Potential via Enhanced Oxidative Phosphorylation and ROS-Mediated Cell Death. (PubMed, J Proteome Res) - "The intracellular and mitochondrial ROS concentrations have also been found to be increased with FACS-based assays. The efficacy of belumosudil observed in the cell-line-based study opens up the possibility of advancing to the next stages of in vivo studies and clinical trials for its use in the treatment of high-grade meningioma, either as a standalone therapy or in combination with other therapeutics."

Journal • Brain Cancer • Meningioma • Oncology • Solid Tumor

Taiwan consensus on pulmonary chronic graft-versus-host disease: A joint statement from the Taiwan Society of Blood and Marrow Transplantation (TBMT) and Taiwan Society of Pulmonary and Critical Care Medicine (TSPCCM). (PubMed, Br J Haematol) - "The fluticasone-azithromycin-montelukast (FAM) regimen has demonstrated notable efficacy in stabilizing lung function. Emerging therapies such as ruxolitinib, belumosudil, abatacept and axatilimab offer promising benefits for refractory cases, whereas lung transplantation is a viable last resort for advanced disease...This consensus report highlights the importance of standardized PFT surveillance, early intervention and individualized immunosuppressive strategies. Future research should focus on refining diagnostic biomarkers and optimizing therapeutic approaches to improve patient outcomes."

Journal • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Critical care • Graft versus Host Disease • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Transplantation

Efficacy and Safety of Belumosudil as Compared with Best Available Therapy for the Treatment of cGVHD in the US. (PubMed, Blood Adv) - "Descriptive assessment of safety showed adverse events recorded in 27% of belumosudil and 36% of BAT LOTs. Findings demonstrated that belumosudil improved clinical outcomes versus BAT in cGVHD patients with 2-5 prior LOTs, and safety was consistent with belumosudil's established profile."

Journal • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology

Atypical Skin Bronzing in Response to Belumosudil for Graft-vs-Host Disease. (PubMed, Cutis) - No abstract available

Journal • Graft versus Host Disease • Immunology

Thailand approves Meiji's REZUROCK for treatment of chronic graft-versus-host disease (Biospectrumasia) - "The approved indication for REZUROCK is the treatment of adult and pediatric patients 12 years and older with chronic graft-versus-host disease (chronic GVHD) after failure of at least two prior lines of systemic therapy."

Approval • Chronic Graft versus Host Disease

A Study to Investigate Safety of Belumosudil in Participants Aged 12 Years and Above, With Chronic Graft-versus-host Disease (cGVHD) (clinicaltrials.gov) - P4 | N=26 | Not yet recruiting | Sponsor: Sanofi

New P4 trial • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology

Design and synthesis of ROCK2-selective inhibitors bearing 6-indazolamino-2-pyrrolidinylpyridine for the treatment of breast cancer metastasis. (PubMed, Bioorg Chem) - "To further enhance the ROCK2 inhibitory activity of belumosudil (ROCK2 IC50 = 0.153 μM), a novel series of 6-indazolamino-2-pyrrolidylpyridine derivatives were designed and synthesized...Mechanistic study suggested that such anti-metastatic effect of S9 was closely related to the suppression of STAT3 phosphorylation. Finally, the binding mode of S9 with ROCK2 well rationalized its superior potency structurally, suggesting the potential application of S9 in breast cancer metastasis treatment."

Journal • Breast Cancer • Oncology • Solid Tumor

Rational Design of 6-Amino-2-Piperazinylpyridine-Based ROCK2 Inhibitors With Anti-Breast Cancer Metastatic Efficiency. (PubMed, Arch Pharm (Weinheim)) - "Guided by the lead compound belumosudil, a novel series of ROCK2 inhibitors based on a 6-amino-2-piperazine pyridine scaffold was designed and synthesized...Additionally, molecular docking studies elucidated the binding mode of 14r within the ROCK2 ATP pocket, corroborating its nanomolar-level inhibitory activity. In conclusion, 14r showed great potential for further optimization to suppress breast cancer metastasis."

Journal • Breast Cancer • Oncology • Solid Tumor

A Study of Belumosudil in Children With Chronic Graft Versus Host Disease (schoolROCK) (clinicaltrials.gov) - P2 | N=37 | Not yet recruiting | Sponsor: Sanofi

New P2 trial • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology

ROCKnrol-1: A Study to Test an Oral Medicine, Belumosudil, in Combination With Corticosteroids in Participants at Least 12 Years of Age With Newly Diagnosed Chronic Graft Versus Host Disease. (clinicaltrials.gov) - P3 | N=260 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

Enrollment closed • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology

Infections in steroid-refractory chronic graft versus host disease patients treated with ruxolitinib, ibrutinib, or belumosudil. (PubMed, Bone Marrow Transplant) - No abstract available

Journal • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • Infectious Disease

Successful use of belumosudil in a patient with chronic ocular GVHD: A case report. (PubMed, Transpl Immunol) - "We report the clinical outcomes of a patient with chronic oGVHD treated with belumosudil. The patient's clinical symptoms significantly improved, especially inflammation of the meibomian gland, corneal leukoplakia, and neovascularization. This highlights its application value in patients with cGVHD and provides a promising treatment option for patients with oGVHD."

Journal • Cataract • Chronic Graft versus Host Disease • Dry Eye Disease • Graft versus Host Disease • Immunology • Inflammation • Ocular Inflammation • Ophthalmology • IL17A • IL21 • TGFB1

Press Release: Q2: double-digit sales and solid business EPS growth. 2025 sales guidance is now high single-digit growth, at upper end of range (GlobeNewswire) - "ALTUVIIIO (hemophilia A) sales were €291 million of which 82% were in the US. Growth was driven by continued patient switches from older plasma-derived and recombinant factor medicines and to a lesser extent from non-factor treatments. Rest of World sales of €53 million benefited from the launch in Japan and supply sales to the collaborator Sobi. The hemophilia A franchise (ALTUVIIIO and Eloctate combined) sales were €356 million and increased by 41.1%, primarily driven by ALTUVIIIO’s strong performance of €291 million, while Eloctate contributed €65 million...Rezurock (chronic graft-versus-host disease, third line) sales were €132 million and increased by 21.1%, driven by launches gaining further momentum in Europe (sales of €14 million) and in Rest of World (sales of €11 million), including in China...Cablivi (acquired thrombotic thrombocytopenic purpura) sales were €69 million...Qfitlia (hemophilia A and B) sales were €1 million..."

Sales • Chronic Graft versus Host Disease • Hemophilia • Hemophilia A • Hemophilia B • Thrombocytopenic Purpura

Rezurock: Regulatory decision in EU for cGVHD in H2 2025 (Sanofi) - Q2 2025 Results

EMA approval • Chronic Graft versus Host Disease • Graft versus Host Disease

Effectiveness of Belumosudil for Chronic Lung Allograft Dysfunction after Lung Transplantation (WTC 2025) - "Belumosudil provided clinical benefit and was well tolerated in patients with CLAD after lung transplantation, demonstrating potential therapeutic effectiveness, particularly in those with early-stage CLAD (stages 1-2)."

Late-breaking abstract • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • Pulmonary Disease • Respiratory Diseases • Transplantation

Simultaneous Pharmacological Inhibition of ROCK2 and HDAC6 Impairs Macrophage Motility and Induces Early Apoptosis through the mTOR/Akt Signaling Pathway (WTC 2025) - "We investigated the effects of dual inhibition on mouse macrophages using a combination of selective inhibitors for HDAC6 and ROCK2, the Ricolonostat (Rico) and Rezurock (Rezu).* Combined treatment affected macrophage cytoskeleton, significantly reducing macrophage migration in wound healing and invasion assays... Combined inhibition of HDAC6 and ROCK2 impairs macrophage migration and proliferation by destabilizing cytoskeletal structures and disrupting cell cycle regulation. This strategy can potentially be used as a novel therapy to treat immune-related disorders, transplant rejection, and graft fibrosis."

Fibrosis • Immunology • Transplant Rejection • CDKN1A • RAC1

“Early access authorization refused for the specialty REZUROCK (belumosudil) in the indication “Treatment of patients aged 12 years and older with chronic graft-versus-host disease (chronic disease (chronic GvHD) after failure of at least two prior lines of systemic treatment” [Google translation] (Haute Autorité de santé)

European regulatory • Graft versus Host Disease • Immunology

Identification and Characterization of Belumosudil Degradation Impurities Using the LC-MS/MS Method and Its Validation. (PubMed, Biomed Chromatogr) - "The formed degradation compounds were identified by using mass spectral data, and plausible fragmentation patterns were proposed by using mass data. This validated stability-indicating assay method confirms its appropriateness for routine analysis and stability investigations of BSL."

Journal • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology

Pharmacokinetics of Belumosudil and Its Metabolites in Individuals With Hepatic Impairment. (PubMed, Clin Transl Sci) - P1 | "Assessment by NCI-ODWG criteria, compared with Child-Pugh criteria, revealed a higher range of exposure in participants with moderate hepatic impairment. Belumosudil can be taken by patients with mild hepatic impairment without dose adjustment; avoid use in patients with moderate hepatic impairment (Child-Pugh B) or severe hepatic impairment (Child-Pugh C) without liver GVHD."

Journal • PK/PD data • Chronic Graft versus Host Disease • Graft versus Host Disease • Hepatology • Immunology • Oncology