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

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

Safety and Efficacy of Oral Belumosudil in Black or African American, American Indian or Alaska Native, and Native Hawaiian or Other Pacific Islander Male and Female Participants Aged 12 Years and Above With Chronic Graft Versus Host Disease (cGVHD) After At Least 2 Prior Lines of Systemic Therapy (clinicaltrials.gov) - P2 | N=36 | Recruiting | Sponsor: Kadmon, a Sanofi Company | Trial completion date: Aug 2025 ➔ Aug 2026 | Trial primary completion date: Aug 2025 ➔ Aug 2026

Trial completion date • Trial primary completion date • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology

Drug and siRNA screens identify ROCK2 as a therapeutic target for ciliopathies. (PubMed, Commun Med (Lond)) - "Our results indicate that specific ROCK2 inhibitors (e.g. belumosudil) could be repurposed for cystic kidney disease treatment. We propose that ROCK2 inhibition represents a novel, disease-modifying therapeutic approach for heterogeneous ciliopathies."

Journal • Genetic Disorders • Nephrology • Polycystic Kidney Disease • Renal Disease

The dual targeting effects of KD025 on casein kinase 2 and ROCK2 in a mouse model of diet-induced obesity. (PubMed, Biochem Pharmacol) - "KD025(belumosudil), a selective ROCK2 inhibitor, exhibits unique anti-adipogenic activity through inhibition of casein kinase 2 (CK2)...C57BL/6 mice on a high fat diet (HFD) were treated with KD025 for 4 weeks, while fasudil (a pan-ROCK inhibitor) and CX-4945 (a CK2-specific inhibitor) served as comparison treatments...Furthermore, KD025 and CX-4945 upregulated adipogenic and browning markers, such as Cebpa, Cidea, and Pparg, in the epiWAT, though without significant UCP1 expression. Overall, KD025 effectively reduced weight gain in HFD-fed mice through dual inhibition of CK2 and ROCK2, highlighting its potential as a therapeutic agent for obesity-related conditions."

Journal • Preclinical • Genetic Disorders • Metabolic Disorders • Obesity • Oncology • CEBPA • IL6 • PPARG • TNFA

A Cry of Defiance and Not of Fear: Emerging CLAD Treatments and Clinical Trials (ISHLT 2025) - "Novel therapies being explored include belumosudil, ruxolitinib, mesenchymal stromal cells, pirfenidone, inhaled sirolimus or cyclosporine, and macitentan. This talk will describe rationale and results from ongoing and planned clinical trials for CLAD."

Clinical • Respiratory Diseases

Neural network analysis as a novel skin outcome in a trial of belumosudil in patients with systemic sclerosis. (PubMed, Arthritis Res Ther) - "Belumosudil was associated with non-clinically meaningful mRSS improvement. The histologic features that significantly correlated with Fibrosis Score changes (e.g., hyalinized collagen, SC fat loss) were distinct from those associated with mRSS changes (e.g., telangiectasia and perivascular CD3 +). These data suggest that AI applied to SSc biopsies may be useful for quantifying pathologic features of SSc beyond skin thickness."

Journal • Dermatopathology • Fibrosis • Immunology • Inflammation • Scleroderma • Systemic Sclerosis • CD8

A Randomized, Placebo-Controlled Phase I Single Ascending Dose Study to Evaluate the Tolerability, Safety, and Pharmacokinetic Profiles of Single-dose BN101 in Healthy Volunteers (ChiCTR) - P1 | N=24 | Completed | Sponsor: Xuzhou Medical University Affiliated Hospital; BioNOVA Pharma

New P1 trial • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology

CLINICALLY MEANINGFUL IMPROVEMENT OF MODIFIED LEE SYMPTOM SCALE IN PATIENTS TREATED WITH BELUMOSUDIL FOR STEROID-REFRACTORY CHRONIC GVHD: EVIDENCE FROM REAL-WORLD OUTCOMES (EBMT 2025) - "Thirteen patients (41%) received BEL/ruxolitinib (RUX) in combination. Prior to BEL, failure to RUX, ibrutinib (IBR) or ECP were noted in 21 (58%), 11 (31%) and 11 patients (31%), respectively... Our findings demonstrate that mLSS is feasible to capture signs of early clinical improvement in cGvHD following BEL treatment before objective response is achieved. There is an urgent need for a practical tool to capture early clinical improvement with the novel agent in cGvHD treatment before achieving objective response by the NIH consensus response criteria. The mLSS has a potential for cGvHD-related symptom burden tracking purpose."

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

CASE SERIES: CHRONIC PULMONARY GRAFT VERSUS HOST DISEASE AFTER HAEMOPOIETIC STEM CELL TRANSPLANT (EBMT 2025) - "There are many therapeutic options including inhalation therapy with fluticasone, azithromycin, montelukast, imatinib, ibrutinib, ruxolitinib, belumosudil, extracorporeal photopheresis (ECP) and lung transplantation...She was managed with fluticasone, montelukast, azithromycin, belumosudil, ciclosporin eye ointment and ECP... All three cases had pulmonary GvHD with bronchiolitis obliterans syndrome. The cases highlight the morbidity and mortality associated with the condition. There was variability in the frequency of lung function monitoring and a pause in monitoring during the COVID-19 pandemic."

Clinical • Asthma • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Cough • Fibrosis • Graft versus Host Disease • Immunology • Infectious Disease • Inflammation • Musculoskeletal Diseases • Myelofibrosis • Novel Coronavirus Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • Transplantation • JAK2

SPANISH REAL WORLD EXPERIENCE (GETH-TC) OF BELUMOSUDIL FOR CHRONIC GRAFT-VERSUS-HOST DISEASE AFTER 2 OR MORE PRIOR LINES OF THERAPY (EBMT 2025) - "Patients had received a median of 4 prior lines of therapy for cGVHD (range 2-10) including ruxolitinib in 59 (94%)...Sixty-one (97%) patients received 200 mg/qd; 2 (3%) received 400 mg due to concomitant treatment with omeprazole... In our real-world experience, including heavily pretreated patients with mostly severe cGVHD, belumosudil treatment was safe and response was consistent to that observed in the pivotal trial."

Clinical • Real-world • Real-world evidence • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Hepatology • Immunology • Infectious Disease • Leukemia • Novel Coronavirus Disease • Oncology • Pneumonia • Respiratory Diseases

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 (EBMT 2025) - P2 | "Patients across all doses and with 0.3 mg/kg had a median (range) of 4 (2-15) and 4 (2-12) prior LOT, respectively; 204 patients (84.6%) across all doses and 67 (83.8%) in the 0.3 mg/kg group had prior cGVHD therapy (ruxolitinib, belumosudil, or ibrutinib). In AGAVE-201, 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

REAL-WORLD PATIENT CHARACTERISTICS AND TREATMENT PATTERNS IN PATIENTS WITH CHRONIC GRAFT-VERSUS-HOST DISEASE RECEIVING BELUMOSUDIL IN THE UNITED STATES (EBMT 2025) - "In this real-world cGVHD cohort, belumosudil was initiated after a median of 489 days from cGVHD diagnosis; most patients received ruxolitinib prior to belumosudil. Most patients received belumosudil in the absence of other cGVHD treatments, and twice-daily dosing was common, possibly owing to concurrent proton pump inhibitor use. Patients had changes (discontinuation/interruption, switch, or add-on) in index belumosudil line of treatment after a median of approximately 4.5 months."

Clinical • Real-world • Real-world evidence • Bone Marrow Transplantation • 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 (EBMT 2025) - P2 | "Patients across all doses and with 0.3 mg/kg had a median (range) of 4 (2-15) and 4 (2-12) prior LOT, respectively; 204 patients (84.6%) across all doses and 67 (83.8%) in the 0.3 mg/kg group had prior cGVHD therapy (ruxolitinib, belumosudil, or ibrutinib). In AGAVE-201, 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

PHASE 1 STUDY OF PACRITINIB, A CSF1R/JAK2/IRAK1 INHIBITOR, FOR REFRACTORY CHRONIC GRAFT-VERSUS-HOST DISEASE: A PRELIMINARY ANALYSIS (EBMT 2025) - P1/2 | "83% were refractory to novel agents including ruxolitinib and belumosudil. Pacritinib, an oral CSF1R/JAK2/IRAK1 inhibitor, has shown a favorable safety profile with promising response rates in a multi-refractory severe CGVHD patients at the initial dose level. Accrual for DL2 is ongoing. Clinical Trial Registry: NCT05531786https://clinicaltrials.gov/study/NCT05531786"

P1 data • Chronic Graft versus Host Disease • Fibrosis • Graft versus Host Disease • Hematological Disorders • Immunology • Infectious Disease • Musculoskeletal Pain • Myelofibrosis • Respiratory Diseases • IRAK1 • JAK2

BELUMOSUDIL IS EFFICACIOUS FOR THE MANAGEMENT OF HEAVILY PRETREATED AND PROLONGED CHRONIC GRAFT-VERSUS-HOST DISEASE: A RETROSPECTIVE MULTI-CENTER STUDY BY THE ISRAEL BONE MARROW TRANSPLANTATION ASSOCIATION (EBMT 2025) - "GVHD prophylaxis included a calcineurin inhibitor and methotrexate in 66.7%, post-transplant cyclophosphamide in 13.3%, and others in 20% of patients...Notably, 86.7% had prior ruxolitinib exposure, and 13.3% concurrently received belumosudil and ruxolitinib... These findings, while comparable to those observed in the ROCKstar trial, are encouraging, considering the heavily pretreated patient population with prolonged severe cGVHD. No new safety signals emerged. Future studies are warranted to optimize patient selection and timing for treatment initiation."

Retrospective data • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Oncology • Pediatrics • Respiratory Diseases • Transplantation

REAL-WORLD TREATMENT PATTERNS OF PATIENTS WITH CHRONIC GRAFT-VERSUS-HOST DISEASE WHO RECEIVED 3 OR MORE LINES OF TREATMENT IN THE UNITED STATES (EBMT 2025) - "cGVHD treatment options have evolved, with multiple contemporary agents (ruxolitinib, belumosudil, ibrutinib, and axatilimab) approved by the US Food and Drug Administration...The most common 2L regimens were ruxolitinib (45.9%), rituximab (14.0%), methotrexate (13.8%), belumosudil (6.3%), and ibrutinib (4.4%)...The most common 3L regimens were ruxolitinib (19.4%), belumosudil (15.0%), and mycophenolate mofetil (12.7%)... Patients with cGVHD started 3L treatment within 1 year of cGVHD diagnosis; a significant proportion (41.3%) required additional treatment. Ruxolitinib was the most common agent used across treatment lines, suggesting its clinical benefit in early settings as well as for salvage therapy after failure of multiple lines of treatment. Combination treatment in later lines of cGVHD were common, suggesting the need to consider cGVHD mechanistic biology and tailoring therapies with nonoverlapping mechanisms of action when considering therapeutic strategy in..."

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

CLINICALLY MEANINGFUL IMPROVEMENT OF MODIFIED LEE SYMPTOM SCALE IN PATIENTS TREATED WITH BELUMOSUDIL FOR STEROID-REFRACTORY CHRONIC GVHD: EVIDENCE FROM REAL-WORLD OUTCOMES (EBMT 2025) - "Thirteen patients (41%) received BEL/ruxolitinib (RUX) in combination. Prior to BEL, failure to RUX, ibrutinib (IBR) or ECP were noted in 21 (58%), 11 (31%) and 11 patients (31%), respectively... Our findings demonstrate that mLSS is feasible to capture signs of early clinical improvement in cGvHD following BEL treatment before objective response is achieved. There is an urgent need for a practical tool to capture early clinical improvement with the novel agent in cGvHD treatment before achieving objective response by the NIH consensus response criteria. The mLSS has a potential for cGvHD-related symptom burden tracking purpose."

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

DESCRIPTION OF PATIENTS AND MANAGEMENT OF CGVHD IN FRANCE BASED ON NATURAL LANGUAGE PROCESSING (NLP) FROM MEDICAL DOCUMENTS AVAILABLE IN HOSPITAL ELECTRONIC MEDICAL FILES (EBMT 2025) - "This study, using an innovative AI-NLP process, provides a first insight into the real-world management of cGVHD in France."

Clinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Gastrointestinal Disorder • Graft versus Host Disease • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

REAL-WORLD PATIENT CHARACTERISTICS AND TREATMENT PATTERNS IN PATIENTS WITH CHRONIC GRAFT-VERSUS-HOST DISEASE RECEIVING BELUMOSUDIL IN THE UNITED STATES (EBMT 2025) - "In this real-world cGVHD cohort, belumosudil was initiated after a median of 489 days from cGVHD diagnosis; most patients received ruxolitinib prior to belumosudil. Most patients received belumosudil in the absence of other cGVHD treatments, and twice-daily dosing was common, possibly owing to concurrent proton pump inhibitor use. Patients had changes (discontinuation/interruption, switch, or add-on) in index belumosudil line of treatment after a median of approximately 4.5 months."

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

REAL-WORLD TREATMENT PATTERNS OF PATIENTS WITH CHRONIC GRAFT-VERSUS-HOST DISEASE WHO RECEIVED 3 OR MORE LINES OF TREATMENT IN THE UNITED STATES (EBMT 2025) - "cGVHD treatment options have evolved, with multiple contemporary agents (ruxolitinib, belumosudil, ibrutinib, and axatilimab) approved by the US Food and Drug Administration...The most common 2L regimens were ruxolitinib (45.9%), rituximab (14.0%), methotrexate (13.8%), belumosudil (6.3%), and ibrutinib (4.4%)...The most common 3L regimens were ruxolitinib (19.4%), belumosudil (15.0%), and mycophenolate mofetil (12.7%)... Patients with cGVHD started 3L treatment within 1 year of cGVHD diagnosis; a significant proportion (41.3%) required additional treatment. Ruxolitinib was the most common agent used across treatment lines, suggesting its clinical benefit in early settings as well as for salvage therapy after failure of multiple lines of treatment. Combination treatment in later lines of cGVHD were common, suggesting the need to consider cGVHD mechanistic biology and tailoring therapies with nonoverlapping mechanisms of action when considering therapeutic strategy in..."

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

SPANISH REAL WORLD EXPERIENCE (GETH-TC) OF BELUMOSUDIL FOR CHRONIC GRAFT-VERSUS-HOST DISEASE AFTER 2 OR MORE PRIOR LINES OF THERAPY (EBMT 2025) - "Patients had received a median of 4 prior lines of therapy for cGVHD (range 2-10) including ruxolitinib in 59 (94%)...Sixty-one (97%) patients received 200 mg/qd; 2 (3%) received 400 mg due to concomitant treatment with omeprazole... In our real-world experience, including heavily pretreated patients with mostly severe cGVHD, belumosudil treatment was safe and response was consistent to that observed in the pivotal trial."

Clinical • Real-world • Real-world evidence • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Disorders • Hematological Malignancies • Hepatology • Immunology • Infectious Disease • Leukemia • Novel Coronavirus Disease • Oncology • Pneumonia • Respiratory Diseases

PHASE 1 STUDY OF PACRITINIB, A CSF1R/JAK2/IRAK1 INHIBITOR, FOR REFRACTORY CHRONIC GRAFT-VERSUS-HOST DISEASE: A PRELIMINARY ANALYSIS (EBMT 2025) - P1/2 | "83% were refractory to novel agents including ruxolitinib and belumosudil. Pacritinib, an oral CSF1R/JAK2/IRAK1 inhibitor, has shown a favorable safety profile with promising response rates in a multi-refractory severe CGVHD patients at the initial dose level. Accrual for DL2 is ongoing. Clinical Trial Registry: NCT05531786https://clinicaltrials.gov/study/NCT05531786"

P1 data • Chronic Graft versus Host Disease • Fibrosis • Graft versus Host Disease • Hematological Disorders • Immunology • Infectious Disease • Musculoskeletal Pain • Myelofibrosis • Respiratory Diseases • IRAK1 • JAK2

BELUMOSUDIL IS EFFICACIOUS FOR THE MANAGEMENT OF HEAVILY PRETREATED AND PROLONGED CHRONIC GRAFT-VERSUS-HOST DISEASE: A RETROSPECTIVE MULTI-CENTER STUDY BY THE ISRAEL BONE MARROW TRANSPLANTATION ASSOCIATION (EBMT 2025) - "GVHD prophylaxis included a calcineurin inhibitor and methotrexate in 66.7%, post-transplant cyclophosphamide in 13.3%, and others in 20% of patients...Notably, 86.7% had prior ruxolitinib exposure, and 13.3% concurrently received belumosudil and ruxolitinib... These findings, while comparable to those observed in the ROCKstar trial, are encouraging, considering the heavily pretreated patient population with prolonged severe cGVHD. No new safety signals emerged. Future studies are warranted to optimize patient selection and timing for treatment initiation."

Retrospective data • Acute Graft versus Host Disease • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Infectious Disease • Leukemia • Oncology • Pediatrics • Respiratory Diseases • Transplantation

BELUMOSUDIL FOR REFRACTORY CHRONIC GVHD IN CHILDREN: A NATIONAL ISRAELI REAL-WORLD STUDY (EBMT 2025) - "The average prednisone dose at the start of belumosudil was 0.5 mg/kg daily, while at the last follow up it was 0.1 mg/kg daily. This is the first collection of real world data on children below the age of 12 with refractory chronic GVHD treated with belumosudil. There was some toxicity and some responses in this very difficult to treat group of patients. Benefits achieved included clinical responses in 40% of patients and reduction of other immune suppressive drugs."

Clinical • Real-world • Real-world evidence • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology • Infectious Disease • Oncology • Pediatrics • Respiratory Diseases • Septic Shock

EFFICACY AND SAFETY OF BELUMOSUDIL AS COMPARED WITH BEST AVAILABLE THERAPY FOR THE TREATMENT OF CHRONIC GRAFT VERSUS HOST DISEASE IN THE US POPULATION (EBMT 2025) - "This study demonstrated that belumosudil has superior efficacy compared with BAT in real-world patients with relapsed/steroid-refractory cGVHD. Safety profile of belumosudil treated patients in this study was consistent with its previously established clinical profile."

Clinical • Chronic Graft versus Host Disease • Graft versus Host Disease • Immunology