Chemistry:Belumosudil

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Belumosudil, sold under the brand name Rezurock among others, is a medication used for the treatment of chronic graft versus host disease (cGvHD).[1][2][3] It is in the class of drugs known as serine/threonine kinase inhibitors.[3] Specifically, it is an inhibitor of Rho-associated coiled-coil kinase 2 (ROCK2; ROCK-II).[4] ROCK2-mediated signaling pathways are major players in pro- and anti-inflammatory immune cell responses. A study in cultured human cells demonstrated that the drug also has effects on oxidative phosphorylation, WNT signaling, angiogenesis, and KRAS signaling.[5]

The most common side effects include infection, tiredness or weakness, nausea, diarrhea, shortness of breath, cough, swelling, bleeding, stomach (abdominal) pain, muscle or bone pain, headache, and high blood pressure.[6]

Belumosudil was approved for medical use in the United States in July 2021.[2][3] The US Food and Drug Administration considers it to be a first-in-class medication.[7]

Medical uses

Belumosudil is indicated for the treatment of people aged twelve years and older with chronic graft-versus-host disease (chronic GVHD) after failure of at least two prior lines of systemic therapy.[2][3]

Chronic graft-versus-host disease is a complication that can occur after stem cell or bone marrow transplantation in which the transplanted donor cells attack the transplant recipient's body.[6]

History

Originally developed by Surface Logix, Inc,[4] belumosudil was later acquired by Kadmon Corporation. By July 2020, the drug completed Phase II clinical studies for cGvHD, IPF, and psoriasis.[8]

Chronic graft-versus-host disease is a complication that can follow allogeneic stem cell or hematopoietic stem cell transplantation where the transplanted cells (graft) attack healthy cells (host). This causes inflammation and fibrosis in multiple tissues. Two cytokines controlled by the ROCK2 signaling pathway, IL-17 and IL-21, have a major role in the chronic graft-versus-host disease response. In a 2016 report using both mouse models and a limited human clinical trial ROCK2 inhibition with belumosudil targeted both the immunologic and fibrotic components of chronic graft-versus-host disease and reversed the symptoms of the disease.[9]

In October 2017, belumosudil was granted orphan drug status in the United States for treatment of people with chronic graft-versus-host disease.[10]

Efficacy of belumosudil was evaluated in clinical trial NCT03640481,[11] a randomized, open-label, multicenter dose-ranging trial that included 65 patients with chronic graft-versus-host disease who were treated with belumosudil 200 mg taken orally once daily.[3][6] A total of eighty-three (83) participants were evaluated for safety; therefore, the number of participants representing efficacy findings may differ from the number of participants representing safety findings due to different pools of study participants analyzed for efficacy and safety.[6] The trial was conducted at 28 sites in the United States.[6]

In July 2021, the US Food and Drug Administration (FDA) approved belumosudil for people aged twelve years of age and older with chronic graft-versus-host disease after failure of at least two prior lines of systemic therapy.[3][7]

Society and culture

In October 2025, the European Medicines Agency (EMA) recommended the refusal of the marketing authorization for Rezurock, a medicine intended for the treatment of chronic graft-versus-host disease (a condition in which donor cells attack the body's organs) after a stem-cell transplant.[12] In January 2026, the Committee for Medicinal Products for Human Use of the EMA, following a re-examination procedure, adopted a positive opinion, recommending the granting of a conditional marketing authorization for the medicinal product Rezurock, intended for the treatment of chronic graft-versus-host disease (cGVHD) in last line patients, aged twelve years of age and older who weigh at least 40 kg (88 lb).[12] The applicant for this medicinal product is Sanofi Winthrop Industrie.[12]

References

  1. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named Rholistiq APM Summary
  2. ↑ 2.0 2.1 2.2 Cite error: Invalid <ref> tag; no text was provided for refs named Rezurock FDA label
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 Cite error: Invalid <ref> tag; no text was provided for refs named FDA belumosudil
  4. ↑ 4.0 4.1 "Comparative gene expression profiling in three primary human cell lines after treatment with a novel inhibitor of Rho kinase or atorvastatin". Blood Coagulation & Fibrinolysis 19 (7): 709–18. October 2008. doi:10.1097/MBC.0b013e32830b2891. PMID 18832915. 
  5. ↑ "Identification of novel functions of the ROCK2-specific inhibitor KD025 by bioinformatics analysis.". Gene 737. 5 May 2020. doi:10.1016/j.gene.2020.144474. PMID 32057928. 
  6. ↑ 6.0 6.1 6.2 6.3 6.4 "Drug Trials Snapshots: Rezurock". 16 July 2021. https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-rezurock.  Public Domain This article incorporates text from this source, which is in the public domain.
  7. ↑ 7.0 7.1 (PDF) Advancing Health Through Innovation: New Drug Therapy Approvals 2021 (Report). 13 May 2022. https://www.fda.gov/media/155227/download. Retrieved 22 January 2023.  Public Domain This article incorporates text from this source, which is in the public domain.
  8. ↑ "KD025 - Clinical Trials". ClinicalTrials.gov. https://clinicaltrials.gov/ct2/results?cond=&term=KD025+Phase+2&cntry=&state=&city=&dist=. 
  9. ↑ "Targeted Rho-associated kinase 2 inhibition suppresses murine and human chronic GVHD through a Stat3-dependent mechanism". Blood 127 (17): 2144–54. April 2016. doi:10.1182/blood-2015-10-678706. PMID 26983850. 
  10. ↑ Shanley, Mathew (6 October 2017). "Therapy to Treat Transplant Complications Gets Orphan Drug Designation". https://www.raredr.com/news/kd025-orphan-drug-designation/. 
  11. ↑ Clinical trial number NCT03640481 for "Efficacy and Safety of KD025 in Subjects With cGVHD After At Least 2 Prior Lines of Systemic Therapy" at ClinicalTrials.gov
  12. ↑ 12.0 12.1 12.2 "Rezurock EPAR". 17 October 2025. https://www.ema.europa.eu/en/medicines/human/EPAR/rezurock.  Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.



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