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

A Clinical Study to Evaluate the Pharmacokinetics, Efficacy, and Safety of Belumosudil in Chinese Adolescents With cGVHD Who Have Had an Inadequate Response to Glucocorticoids or Other Systemic Therapies (clinicaltrials.gov) - P4 | N=6 | Active, not recruiting | Sponsor: Sanofi | Recruiting ➔ Active, not recruiting

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

ANALYSIS OF BASELINE AND CLINICAL CHARACTERISTICS OF EUROPEAN AND ITALIAN PATIENTS WITH CHRONIC GRAFT-VERSUS-HOST DISEASE: INSIGHTS INTO CURRENT TREATMENT LANDSCAPE IN ITALY (EHA 2025) - "While several drugs, such as belumosudil (BEL), are approved for steroid-refractory GvHD (SR-GvHD) in the United States (US), no treatments (tx) are approved in Europe (EU) for patients who fail ≥2 lines of therapy (LOTs). In Italy (IT), patients who fail corticosteroids (CS) and ruxolitinib (RUX) are often managed with off-label therapies as the best available treatment (BAT) beyond the second line... This analysis compares the characteristics of patients with SR-GvHD treated with BAT in EU and IT to identify potential national tx preferences in IT centers. Apart from higher ECP use in IT centers beyond 2 LOTs, no significant differences were observed. This supports that IT subset largely reflects the EU cohort from ROCKreal study."

Clinical • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • Pediatrics

REAL WORLD TREATMENT DURATION IN PATIENTS WITH CHRONIC GRAFT VERSUS HOST DISEASE RECEIVING BELUMOSUDIL COMPARED TO BEST AVAILABLE THERAPY (ROCKREAL) (EHA 2025) - "Prior ruxolitinib use was recorded for 36% of BAT and 68% of belumosudil LOTs, and ruxolitinib was used concomitantly in 49% of BAT LOT and 27% of belumosudil LOT. Leveraging consistent high-quality data captured from large transplant centers in the US, we demonstrated longer treatment duration with belumosudil compared to BAT. The improved treatment continuity in belumosudil arm may be due to better tolerability, efficacy, and patient satisfaction compared to BAT.Reference1, Hall K, et al. Oral presentation, 51st Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT), Florence, Italy, 30 March - 2 April 2025."

Clinical • HEOR • Real-world • Real-world evidence • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology

THE EFFECTS OF PRIOR LINES OF THERAPY ON CLINICAL OUTCOMES FOR PATIENTS WITH CHRONIC GRAFT-VERSUS-HOST DISEASE RECEIVING AXATILIMAB: A POST HOC ANALYSIS OF AGAVE-201 (EHA 2025) - P2 | "Patients across all doses and with 0.3 mg/kg had a median (range) of 4 ( -15) and 4 ( -1 ) prior LOT respectively; 04 patients (85%) across all doses and 67 (84%) in the 0.3 mg/kg group had prior cGVHD therapy (ruxolitinib belumosudil or ibrutinib). In AGAVE- 01 ORRs and response durability with axatilimab were consistent regardless of the number of prior LOT received. Patients who received axatilimab immediately after a regimen with ruxolitinib demonstrated rapid durable clinical responses. Organ-specific responses to axatilimab were noted regardless of last prior therapy and there is a trend toward higher response rates for those treated in their last LOT with ruxolitinib compared with belumosudil in some organs (joints/fascia mouth lungs eyes and skin)."

Clinical • Clinical data • Retrospective data • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • CSF1R

ITALIAN RETROSPECTIVE REAL-LIFE ANALYSIS ON BELUMOSUDIL FOR TREATMENT-RESISTANT/REFRACTORY CHRONIC GVHD (EHA 2025) - "Treatment beyond the second-line relies on new drugs not yet approved in Italy such as belumosudil and axatilimab. This analysis showed the efficacy of belumosudil in a real world setting of heavily pre-treated patients suffering from a mostly severe refractory cGVHD. The drug was well tolerated showing low rate of discontinuation infection and progression of cGVHD. PROs were consistent with objective responses."

Retrospective data • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Fatigue • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Oncology • Respiratory Diseases

UNMET NEEDS IN CHRONIC GRAFT-VERSUS-HOST DISEASE MANAGEMENT: FRENCH SUBSET ANALYSIS OF EUROPEAN PATIENTS WHO PREVIOUSLY RECEIVED 2 TO 5 LINES OF THERAPY (EHA 2025) - "In France the patients who fail corticosteroids and ruxolitinib (RUX) are often treated with off-label alternatives as the best available therapy (BAT) beyond second line...The ROCKreal study a US-based non-interventional RW study evaluated the effectiveness of belumosudil (BEL) vs clinician-chosen BAT for patients with cGVHD who failed –5 prior LOTs (Hall K et al... Across EU and France similar baseline profiles and treatment approaches were observed for patients with cGVHD who failed –5 prior LOTs. Many patients required new treatments even post-RUX. This highlights the need of more effective therapies beyond LOTs which may offer improved outcomes as observed in the comparable RW US patient populations."

Clinical • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology

EFFICACY AND SAFETY OF BELUMOSUDIL MONOTHERAPY AND COMBINATION WITH RUXOLITINIB IN REFRACTORY CHRONIC GRAFT-VERSUS-HOST-DISEASE: A SINGLE CENTRE, REAL-WORLD EXPERIENCE (EHA 2025) - "Despite lower response rates compared to the trial leading to its approval (ROCKstar study) BEL shows reasonable efficacy in the treatment of heavily pretreated cohort of patients with cGVHD. The combination of BEL and Ruxolitinib displayed comparable efficacy. Taking into consideration the potential confounding effect of concurrent liver GVHD BEL demonstrates a satisfactory safety profile."

Clinical • Monotherapy • Real-world • Real-world evidence • Chronic Graft versus Host Disease • Gastrointestinal Disorder • Graft versus Host Disease • Immunology • Infectious Disease

UNMET NEEDS IN CHRONIC GRAFT-VERSUS-HOST DISEASE MANAGEMENT: GREAT BRITAIN SUBSET ANALYSIS OF EUROPEAN PATIENTS TREATED ACROSS 2 TO 5 LINES OF THERAPY (EHA 2025) - "Although belumosudil (BEL) is approved in Great Britain (GB) there is no standardized approach in Europe (EU) for those failing the first lines of therapy (LOTs). In GB patients unresponsive to corticosteroids often use unlicensed alternatives as the best available therapy (BAT) after LOTs with limited use of ruxolitinib (RUX) and BEL (before BEL reimbursement)... Across EU and GB patients with cGvHD who failed -5 prior LOTs exhibited similar baseline profiles and tx approaches yet none of the BAT were effective in halting disease progression. Patients progressed quickly through the initial LOTs but stagnated due to limited tx options not because of improvement. The lack of effective therapies highlights the critical need for alternatives and new tx like BEL may offer improved outcomes as seen in comparable RW US patient populations."

Clinical • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology

THE EFFICACY AND SAFETY OF BELUMOSUDIL IN TREATING PEDIATRIC CHRONIC GRAFT-VERSUS-HOST DISEASE, A REAL-WORLD STUDY (EHA 2025) - "Belumosudil demonstrates good effectiveness and tolerance in the treatment of pediatric cGVHD improving the quality of life for children suffering from cGVHD and reducing the dose of corticosteroids."

Clinical • Real-world • Real-world evidence • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Gastrointestinal Disorder • Graft versus Host Disease • Immunology • Musculoskeletal Pain • Pain • Pediatrics

BELUMOSUDIL FOR CHRONIC GRAFT-VERSUS-HOST DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS (EHA 2025) - "Studies investigated belumosudil alone and the combination of belumosudil with ruxolitinib in patients with steroid-refractory or steroid-dependent cGVHD. Belumosudil demonstrates promising efficacy in heavily pretreated patients with steroid-refractory cGvHD with meaningful overall response rates. This analysis underscores the therapeutic potential of belumosudil in managing steroid-refractory or -dependent cGVHD with rapid response onset and sustained efficacy across multiple organ systems."

Retrospective data • Review • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Gastrointestinal Disorder • Graft versus Host Disease • Immunology

A SINGLE CENTRE EXPERIENCE OF USING BELUMOSUDIL FOR THE TREATMENT OF CHRONIC GRAFT VERSUS HOST DISEASE (EHA 2025) - "7 % of patients were receiving systemic steroids 31% of patients undergoing regular extracorporeal photopheresis and 17% on ruxolitinib. In our patient cohort belumosudil was well tolerated in combination with other immunotherapies and associated with limited toxicity. In line with other studies (ROCKstar Study) the responses observed were partial contributing to an improvement in cGVHD and a reduction in overall immunosuppression. These preliminary findings highlight belumosudil as a promising treatment for this challenging condition."

Clinical • Chronic Graft versus Host Disease • Gastrointestinal Disorder • Graft versus Host Disease • Immunology • Infectious Disease • Musculoskeletal Diseases • Septic Shock

UNMET NEEDS IN CGVHD MANAGEMENT: REAL-WORLD ANALYSIS OF BASELINE AND DISEASE CHARACTERISTICS IN EUROPEAN AND SPANISH PATIENTS PREVIOUSLY TREATED WITH 2 TO 5 LINES OF THERAPY (EHA 2025) - "In the United States (US) belumosudil (BEL) and ibrutinib are approved for patients who fail the first LOTs; however there is no standardized treatment (tx) approach for similar patient populations in Europe (EU) highlighting a significant unmet medical need. In Spain beyond the first LOTs (commonly corticosteroids and Ruxolitinib [RUX]) patients are frequently managed with off-label alternatives as the best available therapy (BAT) for subsequent LOTs... Similar baseline characteristics were observed for EU and Spanish patients who failed -5 prior LOTs. Furthermore given the number of patients receiving -4 LOTs this sub-analysis demonstrated the need for more effective treatment options after LOT- which may offer improved outcomes as observed in the comparable RW US patient populations. Given the severe impact of cGvHD on patient's quality of life and the inadequacy of current therapeutic options novel tx options are urgently required in EU."

Clinical • Real-world • Real-world evidence • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • Pediatrics

Evaluation of the efficacy and safety of belumosudil mesylate tablets in the treatment of chronic graft-versus-host disease in children: An observational study based on real-world data (ChiCTR) - P=N/A | N=30 | Not yet recruiting | Sponsor: Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University; Shanghai Children’s Medical Center, School of Medicine, Sha

New trial • Real-world evidence • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology

BElumosudil for Bronchiolitis Obliterans Prevention/Therapy (BEBOP) (clinicaltrials.gov) - P2 | N=45 | Recruiting | Sponsor: Dana-Farber Cancer Institute | Trial completion date: Dec 2026 ➔ Dec 2027 | Trial primary completion date: Jun 2026 ➔ Jun 2027

Trial completion date • Trial primary completion date • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • Pulmonary Disease • Respiratory Diseases • Transplantation

A Study of Belumosudil in People at Risk of Developing Graft-Versus-Host Disease After a Stem Cell Transplant (clinicaltrials.gov) - P2 | N=46 | Recruiting | Sponsor: Memorial Sloan Kettering Cancer Center

New P2 trial • Graft versus Host Disease • Hematological Malignancies • Immunology • Oncology • Transplantation

Treatment Advances in Steroid-Dependent/Refractory Chronic Graft versus Host Disease : Episode 9: FDA Approvals of Systemic Therapy for Steroid-Refractory cGVHD (Targeted Oncology) - "Panelists discuss how FDA-approved therapies such as ibrutinib, ruxolitinib, belumosudil, and axatilimab provide treatment options for steroid-refractory chronic graft-vs-host disease (cGVHD)."

Video

Changes in Chronic Graft-versus-Host Disease Treatment over Time: A 15-Years Survey within Allogeneic Hematopoietic Stem Cell Transplant Centers in Germany, Austria, and Switzerland. (PubMed, Transplant Cell Ther) - "The survey documents the effect of evidence and approval on clinical care with single agent prednisone representing the standard of care in 1st-line treatment while rux combined with steroids defines the new standard for 2nd-line treatment of cGVHD. ECP is used in case of contraindication for rux and both agents are also used in progressive onset cGVHD. In contrast, treatment of BOS and sclerotic cGVHD beyond 2nd-line treatment remains heterogeneous with new agents being integrated in the treatment landscape."

Journal • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Immunology • Infectious Disease • Pulmonary Disease • Respiratory Diseases • Transplantation

FEV1 Trajectory in a Multicenter Prospective Cohort of Patients With Bronchiolitis Obliterans Syndrome After Hematopoietic Cell Transplantation (ATS 2025) - P | "Current treatments include inhaled corticosteroids (ICS), azithromycin, montelukast, and long-acting beta-agonists ('FAM+LABA' regimen), ± additional systemic immunosuppression (IS)...Initial treatments including IS (e.g. steroids, ruxolitinib, belumosudil, etc.) were tracked... There is heterogeneity in BOS FEV1 trajectories. ppFEV1 at BOS diagnosis and use of systemic therapy did not significantly influence overall progression of BOS in our cohort. Additional work is needed to further elucidate factors that influence BOS phenotypes."

Clinical • Pulmonary Disease • Respiratory Diseases • Transplantation

Role of ROCK2 inhibitors in the Treatment of Chronic Graft-versus-Host disease. (PubMed, Expert Opin Investig Drugs) - "This includes a review of the current and ongoing clinical data with belumosudil, and an overview of current ROCK2 inhibitors in development for cGVHD including rovadicitinib, zelasudil and GV-101. Many of the recent novel agents with unique mechanisms such as ROCK2 inhibitors (i.e. belumosudil) provide high response rates but rarely yield complete responses in cGVHD. The future of management of cGVHD will rely on investigating combination therapy upfront that may achieve deeper complete responses, developing newer preventative therapies, and advancements in biomarker detection/risk stratification for cGVHD."

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

Inhibition of Rho-associated kinases ROCK1 and ROCK2 as a Therapeutic Strategy to Reactivate the Repressed FXN Gene in Friedreich Ataxia. (PubMed, J Neurosci) - "Treatment with small-molecule ROCK inhibitors, including the FDA-approved drug belumosudil and clinically advanced fasudil, restores frataxin levels, alleviates mitochondrial defects, and improves disease phenotypes in cells and animal models. These findings establish ROCK kinases as targets for Friedreich ataxia therapy and open new avenues for repurposing existing ROCK inhibitors, warranting clinical exploration."

Journal • Ataxia • Cardiomyopathy • Cardiovascular • CNS Disorders • Friedreich ataxia • Metabolic Disorders • Movement Disorders • FXN

Evaluating Axatilimab as a treatment option for chronic graft-versus-host disease. (PubMed, Immunotherapy) - "In recent years, newer treatments including ruxolitinib and belumosudil have shown success in the second and third line settings. CSF1R signaling dependent macrophages and monocytes are key mediators of inflammation and fibrosis in chronic GVHD, and thus, this therapy offers a targeted approach. Here we summarize the key clinical studies that have been performed to date of this novel therapy."

Journal • Review • Chronic Graft versus Host Disease • Fibrosis • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Immunology • Oncology • Transplantation • CSF1R

Belumosudil for Chronic Graft-Versus-Host Disease: Analysis of Long-Term Results From the KD025-208 and ROCKstar Studies. (PubMed, Transplant Cell Ther) - P2, P2a | "When compared with the published data, the long-term results from this pooled analysis of these two phase 2 studies demonstrated belumosudil was associated with durable responses, and it remained well tolerated with no new safety concerns."

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

Real-world use of belumosudil: Key insights and future perspectives (YouTube) - "The GvHD Hub spoke to Corey Cutler...about his key insights into real-world use of belumosudil."

Video

Belumosudil reduces oral chronic graft-versus-host disease tissue inflammation and fibrosis: a ROCKstar companion study. (PubMed, Blood Adv) - P2 | "These findings illustrate the tissue-level response to belumosudil therapy and suggest that there is a reduction in tissue fibrosis and inflammation, thereby highlighting the therapeutic impact of ROCK2 inhibition in mitigating cGVHD. The ROCKstar study was registered at www.clinicaltrials.gov as NCT03640481."

Journal • Chronic Graft versus Host Disease • Fibrosis • Graft versus Host Disease • Immunology • Inflammation • CD4 • IL17A • TGFB1

Press Release: Sanofi: strong Q1 performance and 2025 guidance confirmed (Sanofi Press Release) - "Rezurock (chronic graft-versus-host disease) sales were €131 million and increased by 36.6%, driven by the US (+31.0%) from solid volume growth and by launches gaining momentum in Europe (sales of €9 million) and in Rest of World (sales of €9 million). Cablivi (acquired thrombotic thrombocytopenic purpura) sales were €67 million and increased by 11.9%, driven by more patients being identified for treatment, aided by using artificial intelligence in the US and from launches in Europe and Rest of World."

Sales • Chronic Graft versus Host Disease • Thrombocytopenic Purpura