Belumosudil with ROCK-2 inhibition: chemical and therapeutic development to FDA approval for the treatment of chronic graft-versus-host disease - 07/05/22
Highlights |
• | BLM is a ROCK inhibitor being developed by Surface Logix, later acquired by Kadmon Pharmaceuticals for the treatment of chronic graft-versus-host disease (cGVHD), diffuse cutaneous systemic sclerosis (dcSSc), and idiopathic pulmonary fibrosis (IPF). |
• | It is the first and only drug that targets the Rho-associated coiled-coil kinase (ROCK) 2 signaling pathway, which primarily regulates inflammatory response and fibrotic processes. |
• | BLM received its first FDA Approval on 16th July 2021 in the United States for the treatment of cGVHD in adult and pediatric patients aged ≥ 12 years after the failure of at least two prior lines of systemic therapy. |
• | It has been granted orphan drug status in European Union on 17th October 2019 for the treatment of cGVHD. |
• | BLM is under regulatory assessment by Therapeutic Good Administration (TGA) Australia, Health Canada, MHRA (UK), and The Swiss Agency for Therapeutic Products (Swissmedic), Switzerland for cGVHD. A clinical trial is ongoing in the United States for cutaneous systemic sclerosis. |
Abstract |
Belumosudil (BLM) is a ROCK inhibitor that has been firstly developed by Surface Logix, later acquired by Kadmon Pharmaceuticals for the treatment of chronic graft-versus-host disease (cGVHD), Psoriasis Vulgaris (PV), idiopathic pulmonary fibrosis (IPF), hepatic impairment (HI), diffuse cutaneous systemic sclerosis (dcSSc). BLM received a breakthrough therapy designation and priority review from the FDA, which reviewed the NDA under the real-time oncology review (RTOR) pilot programme and approved it six weeks ahead of the PDUFA deadline of August 30, 2021. On July 16th, 2021, The USFDA authorized BLM under the brand name REZUROCKTM for the treatment of cGVHD in adults and pediatric patients aged ≥ 12 years after the failure of at least two prior lines of systemic therapy. It has been granted orphan drug status by the FDA on August 9, 2020, for the treatment of systemic sclerosis. The European Union (EU) granted Quality Regulatory Clinical Ireland Limited, Ireland, orphan drug status for BLM (KD025) for the treatment of cGVHD on October 17, 2019. BLM is under regulatory assessment by Therapeutic Good Administration (TGA) Australia, Health Canada, MHRA (UK), and The Swiss Agency for Therapeutic Products (Swissmedic), Switzerland for cGVHD. A clinical trial is ongoing in the United States for cutaneous systemic sclerosis. This review article summarizes the milestones in the development of BLM chemistry, Chemical synthesis and development, mechanism of action, pharmacokinetics (PK), pharmacodynamics (PD), adverse effects, regulatory status, and ongoing clinical trials (CT) of BLM.
El texto completo de este artículo está disponible en PDF.Keywords : Belumosudil, cGVHD, REZUROCKTM, KD025, SLx-2119, Kinase Inhibitor, Rock-2 Inhibitor, BLM, ROCK, Chronic Graft-Versus-Host Disease
Abbreviations : BLM, cGVHD, ROCK, TNF-α, STAT-3, STAT-5, Th17, Treg, MOA, AUC, CV, CT, CI, CR, PR, ORR, PK, PD, BA, IPF, dcSSc, NDA, HPBL, PPIs, eGFR, FDA
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Vol 70 - N° 3
Artículo 103343- juillet 2022 Regresar al número
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