Methods of administering Belumosudil for treatment of chronic graft versus host disease
Inventors
Eiznhamer, David • Krenz, Heidi
Assignees
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Publication Number
US-12097202-B2
Publication Date
2024-09-24
Expiration Date
Abstract
The present disclosure provides methods of administering belumosudil mesylate salt to patients with chronic graft-versus-host disease (cGVHD), wherein the methods include identifying adverse reactions in the patients, such as an infection, and modifying the administration based on the results of such identification, such as by ceasing administration when the infection is a Grade 3 or Grade 4 level infection.
Core Innovation
The invention describes a method of treating chronic graft-versus-host disease (cGVHD) in a patient in need thereof. The method comprises administering 2-{3-[4-(1H-indazol-5-ylamino)-2-quinazolinyl]phenoxy}-N-(propan-2-yl) acetamide, or a pharmaceutically acceptable salt thereof, at a daily dose equivalent to 200 mg of the free base of the Compound. The disclosure further characterizes belumosudil as an oral ROCK2/ROCK1 inhibitor with immunomodulatory and anti-fibrotic effects.
The method includes identifying an adverse reaction in the patient, wherein the adverse reaction is an infection. A risk-management dosing rule is applied using adverse reaction grading (CTCAE v5.0) based on infection level. When an infection is at a Grade 3 level, administration of the Compound is ceased; when the infection has recovered to Grade 1 level or less, administration is resumed at the previously administered daily dose.
The disclosure also defines a second adverse-reaction threshold for severe infection. When an infection is at a Grade 4 level, administration of the Compound is permanently ceased, with Grade 4 defined as life-threatening infection requiring urgent intervention. The partial content frames these rules within clinical and safety evidence from phase II studies, including outcomes such as overall response rate (ORR) and infection-related adverse reaction frequencies.
Claims Coverage
The partial content identifies two independent claims directed to treating chronic graft-versus-host disease (cGVHD) with the specified Compound at a daily dose equivalent to 200 mg free base, combined with infection adverse-reaction grading to manage dosing. Across the independent claims, the inventive features center on compound administration at the specified daily dose equivalence, infection grading-based dose interruption versus permanent discontinuation, and the definitions of Grade 3 and Grade 4 infection thresholds.
Daily dose equivalent to 200 mg free base administration of the Compound
Administering 2-{3-[4-(1H-indazol-5-ylamino)-2-quinazolinyl]phenoxy}-N-(propan-2-yl) acetamide, or a pharmaceutically acceptable salt thereof, to the patient at a daily dose that is equivalent to 200 mg of the free base of the Compound.
Infection adverse reaction identification and Grade 3 treatment interruption with resumption
Identifying an adverse reaction in the patient wherein the adverse reaction is an infection; ceasing administration of the Compound when the adverse reaction is an infection at a Grade 3 level; and resuming administration of the Compound at the previously administered daily dose when the patient's infection has recovered to Grade 1 level or less.
Grade 4 infection permanent discontinuation
Identifying an adverse reaction in the patient wherein the adverse reaction is an infection; permanently ceasing administration of the Compound when the patient's adverse reaction comprises a Grade 4 level infection, wherein Grade 4 level infection is life-threatening and wherein urgent intervention is indicated.
Both independent claims implement infection adverse-reaction grading to manage belumosudil administration in cGVHD: ceasing dosing for Grade 3 infections with resumption after recovery to Grade 1 or less, and permanently ceasing for Grade 4 infections that are life-threatening and require urgent intervention, while administering the Compound at a daily dose equivalent to 200 mg of the free base.
Stated Advantages
Cessation and resumption, or permanent discontinuation, of Compound administration based on infection adverse reaction grading (Grade 3 versus Grade 4) as a risk-management rule.
Documented Applications
Treating chronic graft-versus-host disease (cGVHD) in a patient in need thereof, including monitoring for infection adverse reactions and applying infection-grade based dosing interruption and resumption rules.
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