贝舒地尔主要用于治疗什么？

(belumosudil) is indicated for the treatment of pediatric (≥12 years old) and adult patients with chronic graft-versus-host disease (cGVHD) who have failed at least 2 systemic therapies.

About Besudil

1. In October 2017, Besudil was granted orphan drug designation for the treatment of cGVHD by the U.S. Food and Drug Administration (FDA);

2. In October 2018, Besudil was granted breakthrough therapy designation by the FDA for the treatment of cGVHD;

3. In October 2019, it was granted orphan drug designation for the treatment of cGVHD by the European Medicines Agency (EMA);

4. In September 2020, it was granted orphan drug designation by the FDA for the treatment of systemic sclerosis;

5. In November 2020, the US FDA accepted belu-mosudil 6. On July 16, 2021, the FDA approved belumosudil for the treatment of children (age ≥ 12 years old) and adult patients with cGVHD who have failed treatment with at least 2 systemic therapies.

For more information about Besudil, please refer to: This article details the price information of Besudil.

The role of besudil

belumosudil is a selective oral ROCK2 inhibitor, which exists in the form of mesylate. Its selectivity for ROCK2 is 100 times that of ROCK1; the maximum half-inhibitory concentration (IC50) of ROCK2 and ROCK1 is approximately 100 and 3 umol/L respectively. Belumosudil inhibits signal transducer and activator of transcription 3 (STAT3) phosphorylation, upregulates STAT5 phosphorylation, and shifts the T helper cell 17 (TTh17)/T regulatory cell (Treg) balance toward the Treg phenotype, thereby downregulating the pro-inflammatory response.

The therapeutic effect of besudil

An open-label, multi-center, dose-finding phase IIa clinical trial (NCTO2841995) evaluated the efficacy of belumosudil in patients with cGVHD who had previously received 1 to 3 lines of therapy [1].

A total of 54 patients with cGVHD were included in the study and randomly assigned to three dose groups: 200 mg QD (n = 17), 200 mg BID (n = 16) and 400 mg QD (n = 21) until disease progression or intolerable toxicity.

The primary endpoint was ORR, and secondary endpoints included the number and percentage of steroid-dependent cGVHD patients achieving complete remission or partial remission, DOR, organ system response rate, change in Lee symptom scale score, change in corticosteroid dose, time to next treatment (TTNT), FFS, and OS.

The results showed that the overall median follow-up time was 29 months, and the ORRs of the 200 mg QD group, 200 mg BID group and 400 mg QD group were 65%, 69% and 62% respectively. Median time to response was 35 weeks; 50% of patients had a clinically meaningful improvement in LSS score; 67% of patients had their corticosteroid dose reduced and 19% discontinued corticosteroids. The average TTNT is 14 months. The FFS rates at 6 months, 12 months and 24 months were 76%, 47% and 33% respectively, and the 2-year OS rate was 82%.

Besudil usage and dosage

The approved dosage form of Belumosudil is tablets, with a specification of 200 mg per tablet. The recommended dose is 200 mg orally, once a day, with food, until disease progression requires new systemic treatment. If patients are concurrently receiving strong CYP3A inducers or proton pump inhibitors, the dose of belumosudil should be increased to 200 mg twice daily.

Adverse reactions of besudil

The most common (≥20%) adverse reactions of besudil are infection, fatigue, nausea, diarrhea, dyspnea, cough, edema, bleeding, abdominal pain, musculoskeletal pain, headache, decreased phosphate, increased gamma-glutamyl transferase, decreased lymphocytes, and hypertension.

Summary

Besudil was approved by the FDA to be included in the treatment of cGVHD, which is an important progress in the treatment of cGVHD.

Besudil has the advantage of being convenient to take. Its high response rate, good safety and tolerability mean that patients with cGVHD can obtain clinically meaningful benefits.

References

[1] Li Mupeng, Fan Lianlian. New drug ROCK2 inhibitor Belumosudil for the treatment of chronic graft-versus-host disease [J]. Strait Pharmacy, 2023, 35(01):137-140.

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