General Information

Rezurock (belumosudil) is a kinase inhibitor.

Rezurock is specifically indicated for the treatment of adult and pediatric patients 12 years and older with chronic graft-versus-host disease (chronic GVHD) after failure of at least two prior lines of systemic therapy.

Rezurock is supplied as tablets for oral administration. The recommended dose is 200 mg given orally once daily until progression of chronic GVHD that requires new systemic therapy. Tablets should be swallowed whole. Do not cut, crush, or chew tablets. Take Rezurock with a meal at approximately the same time each day. If a dose is missed, instruct the patient to not take extra doses to make up the missed dose.

Treatment with Rezurock has not been studied in patients with pre-existing severe renal or hepatic impairment. For patients with pre-existing severe renal or hepatic impairment, consider the risks and potential benefits before initiating treatment.

Mechanism of Action

Rezurock (belumosudil) is an inhibitor of rho-associated, coiled-coil containing protein kinase (ROCK) which inhibits ROCK2 and ROCK1 with IC50 values of approximately 100 nM and 3 µM, respectively. Belumosudil downregulated proinflammatory responses via regulation of STAT3/STAT5 phosphorylation and shifting Th17/Treg balance in ex-vivo or in vitro-human T cell assays. Belumosudil also inhibited aberrant pro-fibrotic signaling, in vitro. In vivo, belumosudil demonstrated activity in animal models of chronic GVHD.

Side Effects

Adverse effects associated with the use of Rezurock may include, but are not limited to, the following:

• asthenia
• nausea
• diarrhea
• dyspnea
• cough
• edema
• hemorrhage
• abdominal pain
• musculoskeletal pain
• headache
• phosphate decreased
• gamma glutamyl transferase increased
• lymphocytes decreased
• hypertension

Clinical Trial Results

The FDA approval of Rezurock was based on safety and efficacy results from ROCKstar (KD025-213), a randomized, open-label, multicenter pivotal trial of in patients with cGVHD who had received two to five prior lines of systemic therapy. There were 65 patients treated with Rezurock 200 mg taken orally QD. The median time from cGVHD diagnosis was 25.3 months and 48% of patients had four or more organs involved. Patients had cycled through a median of 3 prior lines of systemic therapy and 78% were refractory to their last therapy. Rezurock 200 mg QD achieved an Overall Response Rate (ORR) of 75% through Cycle 7 Day 1 of treatment, with 6% achieving a complete response and 69% achieving a partial response. The median time to first response was 1.8 months. Sixty-two percent (62%) of responders did not require new systemic therapy for at least 12 months following response. The median duration of response, calculated from first response to progression, death, or new systemic therapies for chronic GVHD, was 1.9 months. ORR results were supported by clinically meaningful improvement from baseline in the Lee Symptom Scale (LSS) score, a chronic GVHD symptom measurement, in 52% of patients through Cycle 7 Day 1 of treatment.