Belumosudil: First Approval

Blair, Hannah A.

doi:10.1007/s40265-021-01593-z

Cited by 36 publications

(34 citation statements)

References 6 publications

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“…16 Safety and efficacy have been demonstrated in phase 2 trials using a dose regimen with food; as such, belumosudil should be administered with a meal. 13 In addition to food effect, the relative bioavailability of the 2 formulations was assessed under fed conditions. For both the tablet and capsule, belumosudil was quickly absorbed and eliminated, as evidenced by rapid appearance of metabolites KD025m1 and KD025m2.…”

Section: Discussionmentioning

confidence: 99%

“…12 Belumosudil (REZUROCK) is a selective ROCK2 inhibitor approved for the treatment of adults and pediatric patients (≥12 years of age) with cGVHD after failure of at least 2 prior lines of therapy. 13 Early clinical trials with belumosudil employed a capsule formulation consisting of the active pharmaceutical ingredient belumosudil mesylate, encapsulated without excipients in opaque hard yellow gelatin shells. To facilitate manufacturing scalability, a tablet formulation was subsequently developed with the intent of matching the capsule's immediate release profile.…”

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confidence: 99%

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Phase 1 Studies to Evaluate the Food Effect and Relative Bioavailability of Tablet and Capsule Formulations of Belumosudil in Healthy Adult Subjects

Schueller¹,

McDermott

Evans

et al. 2022

Clinical Pharm in Drug Dev

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Belumosudil is a selective Rho‐associated coiled‐coil containing protein kinase 2 inhibitor. A capsule formulation was used during early clinical development of belumosudil; it was later replaced by a tablet formulation, which mimicked the capsule's release properties and facilitated manufacturing scalability. To assess belumosudil's pharmacokinetics, including potential food effects, and evaluate the relative bioavailability of the 2 formulations, 2 phase 1 clinical trials were conducted. Administration of both belumosudil tablets and capsules with food increased exposure ≈2× as compared to the fasted state and delayed time to maximum concentration by 0.5 hour, indicating a decrease in the rate but increase in the extent of absorption with fed administration. Relative bioavailability was slightly higher when belumosudil was administered as tablets vs capsules, although the difference was not clinically meaningful. Safety and tolerability were generally consistent with the known safety profile of belumosudil. The results of these studies support administration of belumosudil with food.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Phase 1 Studies to Evaluate the Food Effect and Relative Bioavailability of Tablet and Capsule Formulations of Belumosudil in Healthy Adult Subjects

Schueller¹,

McDermott

Evans

et al. 2022

Clinical Pharm in Drug Dev

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“…Therefore, ROCK2 inhibition has emerged as a promising therapeutic for the treatment of cGVHD 7 . Belumosudil (REZUROCK) is an orally available selective ROCK2 inhibitor approved for the treatment of adult and pediatric patients aged ≥12 years with cGVHD after failure of at least 2 prior lines of systemic therapy 8 …”

mentioning

confidence: 99%

“…7 Belumosudil (REZUROCK) is an orally available selective ROCK2 inhibitor approved for the treatment of adult and pediatric patients aged ≥12 years with cGVHD after failure of at least 2 prior lines of systemic therapy. 8 Belumosudil undergoes metabolism to form a ROCK2-active metabolite, KD025m1, and a metabolite that is relatively less active against ROCK2, KD025m2. The inactive metabolite KD025m2 is the only identified major metabolite in humans.…”

mentioning

confidence: 99%

A Phase 1 Pharmacokinetic Drug Interaction Study of Belumosudil Coadministered With CYP3A4 Inhibitors and Inducers and Proton Pump Inhibitors

Schueller¹,

Willson

Singh

et al. 2022

Clinical Pharm in Drug Dev

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Belumosudil is a selective Rho-associated protein kinase 2 inhibitor. Inhibition of Rho-associated protein kinase 2 has emerged as a promising treatment for chronic graft-versus-host disease by restoring immune homeostasis and reducing fibrosis. In vitro assessments have suggested that metabolism of belumosudil is primarily dependent on cytochrome P450 (CYP) 3A4 activity and that the solubility of belumosudil is pH dependent. As such, this 2-part clinical drug-drug interaction study was conducted to assess the effect of itraconazole (a strong CYP3A4 inhibitor), rifampicin (a strong CYP3A4 inducer), rabeprazole, and omeprazole (both proton pump inhibitors) on the pharmacokinetics of belumosudil. No clinically relevant change in belumosudil exposure was observed following a 200-mg single oral dose of belumosudil with itraconazole; however, exposure of main metabolite, KD025m2, was decreased. Consistent with the proposed metabolic pathway of belumosudil, the strong CYP3A4 inducer rifampicin significantly decreased exposure of belumosudil and KD025m2 and increased KD025m1 exposure. When a 200-mg single oral dose of belumosudil was coadministered with both rabeprazole and omeprazole, parent and metabolite exposures were largely reduced, suggesting that belumosudil dosage should be increased when given with PPIs. Administration of belumosudil with and without perpetrator drugs was safe, and no notable adverse events were reported.

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“…Belumosudil is well-tolerated and clinically beneficial (Cutler et al 2021 ; Jagasia et al 2021 ). Its common AEs include infections, asthenia, nausea, diarrhea, dyspnea, cough, edema, hemorrhage, abdominal pain, musculoskeletal pain, headache, decreased phosphate, increased γ glutamyl transferase, decreased lymphocytes, and hypertension (Blair 2021a ).…”

Section: Methodsmentioning

confidence: 99%

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2021

Kaykı-Mutlu

Aksoyalp

Wojnowski

et al. 2022

Naunyn-Schmiedeberg's Arch Pharmacol

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The second year of the COVID-19 pandemic had no adverse effect on the number of new drug approvals by the US Food and Drug Administration (FDA). Quite the contrary, with a total of 50 new drugs, 2021 belongs to the most successful FDA years. We assign these new drugs to one of three levels of innovation: (1) first drug against a condition (“first-in-indication”), (2) first drug using a novel molecular mechanism (“first-in-class”), and (3) “next-in-class”, i.e., a drug using an already exploited molecular mechanism. We identify 21 first-in-class, 28 next-in-class, and only one first-in-indication drugs. By treatment area, the largest group is once again cancer drugs, many of which target specific genetic alterations. Every second drug approved in 2021 targets an orphan disease, half of them being cancers. Small molecules continue to dominate new drug approvals, followed by antibodies and non-antibody biopharmaceuticals. In 2021, the FDA continued to approve drugs without strong evidence of clinical effects, best exemplified by the aducanumab controversy.

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Belumosudil: First Approval

Cited by 36 publications

References 6 publications

Phase 1 Studies to Evaluate the Food Effect and Relative Bioavailability of Tablet and Capsule Formulations of Belumosudil in Healthy Adult Subjects

Phase 1 Studies to Evaluate the Food Effect and Relative Bioavailability of Tablet and Capsule Formulations of Belumosudil in Healthy Adult Subjects

A Phase 1 Pharmacokinetic Drug Interaction Study of Belumosudil Coadministered With CYP3A4 Inhibitors and Inducers and Proton Pump Inhibitors

A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2021

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