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Besudil mesylate tablets are a drug for the treatment of chronic graft-versus-host disease (cGvHD). Besudil mesylate tablets can inhibit the ROCK2 enzyme, reduce the activation of immune cells, improve the inflammatory response, and achieve the effect of treating cGvHD.

The treatment effect is better. Clinical studies show that the overall objective response rate of besudil mesylate tablets in the treatment of cGvHD is 75%, the median duration of response is 1.9 months, and the median time to first response is 1.8 months. Among patients who achieved remission, 62% were free of death or initiation of new systemic therapy for at least 12 months after remission.

Chronic graft-versus-host disease

Chronic graft-versus-host disease is a multisystem disease in which up to 70% of patients are diagnosed after allogeneic hematopoietic cell transplantation. In cGvHD, donor immune cells attack the patient's cells, causing inflammation and fibrosis in multiple tissues. cGvHD can affect almost any organ and is a major cause of morbidity and mortality in transplant survivors.

Rho-related coiled-coil protein kinase (ROCK) is a signaling pathway that regulates inflammatory responses and fibrotic processes and is dysregulated in autoimmune diseases. Many inhibitors targeting the ROCK pathway have been studied, but most lack isoform selectivity, resulting in dose-limiting effects.

Indications of Besudil Mesylate Tablets

Besudil Mesylate Tablets is a selective oral ROCK2 inhibitor that has been proven to be safe and effective against cGvHD.

It has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult and pediatric cGvHD patients aged 12 years and older after failure of at least two lines of systemic therapy, becoming the first and only approved therapy targeting ROCK2.

Efficacy and effects of Besudil Mesylate Tablets

Besudil Mesylate Tablets is an investigational oral selective Rho-associated coiled-coil protein kinase 2 inhibitor that reduces type 17 and follicular T helper cells by down-regulating STAT3, and enhances regulatory T cells by up-regulating STAT5.

Besudil mesylate tablets can effectively treat patients with chronic graft-versus-host disease (cGVHD), which is a major cause of morbidity and late non-relapse mortality after allogeneic hematopoietic cell transplantation.

Besudil Mesylate Tablets Side Effects

The most common side effects are infection, fatigue, nausea, bleeding, abdominal pain, decreased lymphocytes and hypertension, musculoskeletal pain, cough, edema, headache, decreased phosphate, diarrhea, dyspnea, and increased gamma-glutamyl transferase.

Clinical efficacy of Besudil mesylate tablets

Purpose: The rho-related coiled-coil protein kinase-2 signaling pathway regulates Th17/regulatory T cell balance and controls the pro-fibrotic pathway. Selective inhibition of ROCK2 with besudil mesylate tablets (KD025) may provide a new method for the management of chronic graft-versus-host disease (cGVHD).

Patients and Methods: This phase IIa, open-label, dose-finding study of besudil mesylate tablets enrolled 54 patients with cGVHD who had received 1-3 prior treatment regimens. The primary endpoint was overall response rate (ORR).

Results: The overall median follow-up time was 29 months. The ORRs of besudil mesylate tablets 200 mg once daily, 200 mg twice daily and 400 mg once daily were 65%, 69% and 62% respectively.

Responses were clinically meaningful, with a median duration of response of 35 weeks, and were associated with improved quality of life and corticosteroid (CS) dose reduction. 19% of patients discontinued CS treatment. The 6-month and 12-month failure-free survival rates were 76% and 47%, respectively, and the 2-year overall survival rate was 82%.

Besudil mesylate tablets are well tolerated and have low cytopenia rate. There were no unexpected adverse events and no significant increased risk of infection, including cytomegalovirus infection and reactivation.

Conclusion: Besudil mesylate tablets can improve the ORR and overall survival of patients, and can also reduce the dosage of CS, with limited toxic and side effects, and can improve the quality of life of patients. Research data suggest that besudil mesylate tablets may be an effective treatment for patients with refractory cGVHD.

Summary

The indication of Besudil mesylate tablets is chronic graft-versus-host disease. It can exert a therapeutic effect by inhibiting coiled-coil protein kinase, improve inflammatory response, resist vasoconstriction, and promote the formation of new blood vessels. Besudil mesylate tablets have clinically shown good efficacy and good safety.

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