dm+d

Unassigned

New Medicines

RezurockChronic graft versus host disease (GvHD) after failure of two or more lines of systematic therapy

Information

Rezurock
New molecular entity
Sanofi
Sanofi

Development and Regulatory status

Approved (Licensed)
None
Launched
Yes
Yes
Aug 22MHRA grants an orphan designation to belumosudil [13]
Jul 22Approved for use in the UK for the treatment of pts aged 12 years and older with chronic graft-versus-host disease (chronic GVHD) who have received at least two prior lines of systemic therapy [12]
Sep 21Sanofi enters into a definitive merger agreement with Kadmon Holdings and immediately adds Rezurock to its transplant portfolio [8].
Aug 21Launched in US [8].
Jul 21In the US, Kadmon announces the FDA has approved belumosudil for the treatment of adult and pediatric patients 12 years and older with chronic graft-versus-host disease (cGVHD) after failure of at least two prior lines of systemic therapy. The NDA was reviewed under the Real-Time Oncology Review (RTOR) pilot programme and under Project Orbis. For the review, the US FDA collaborated with regulatory agencies in Australia, Canada, Switzerland and the UK [6,7].
Nov 20Filed in UK under project ORBIS [9,10].
Nov 20The FDA granted Priority Review for the NDA for belumosudil for the treatment of cGVHD and assigned a PDUFA target action date of August 30, 2021.[2,3]
Oct 19Awarded Orphan Drug status in EU [11].
Oct 18US FDA has granted Breakthrough Therapy Designation to belumosudil for the treatment of pts with cGVHD after failure of two or more lines of systemic therapy as well as Orphan Drug Designation to belumosudil for the treatment of cGVHD.[3]

Category

In cGVHD, transplanted graft cells attack host cells, leading to inflammation & fibrosis. This selective oral inhibitor of Rho-associated coiled-coil kinase 2 (ROCK2), a signaling pathway that modulates inflammatory response & pro-fibrotic processes.[2,3]
The number of allogeneic bone marrow and stem cell transplants is increasing worldwide. Graft-versus-host disease (GvHD) is a serious complication of this type of transplant. The incidence of acute GvHD varies widely, ranging from 10-80% depending on risk factors [1].
Chronic graft versus host disease (GvHD) after failure of two or more lines of systematic therapy
Oral

Trial or other data

Apr 22Sanofi releases pooled data from two trials of Rezurock that show a strong correlation between certain organ responses and improvements in patient-reported outcomes. The clinically meaningful changes in PROs were reported in the skin, mouth, eye, lung, upper gastrointestinal and overall measures [9].
Apr 21Results from KD025-208, the PIIa trial of belumosudil (n=54) pts in the US with cGVHD who had received 1-3 prior lines of therapy were published in the Journal of Clinical Oncology. With an overall median follow-up of 29 months, the ORR (95% CI) with belumosudil 200 mg once daily, 200 mg twice daily, and 400 mg once daily was 65% (38% to 86%), 69% (41% to 89%), and 62% (38% to 82%), respectively. Median duration of response was 35 weeks, and improvement was noted in quality-of-life corticosteroid use. The 2-year overall survival rate was 82% (69% to 90%). Belumosudil was well-tolerated, with low rates of cytopenia. There were no unexpected adverse events and no apparent increased risk of infection, including cytomegalovirus infection and reactivation. [5]
Oct 18Pivotal open label, randomised PII ROCKstar trial (NCT03640481; KD025-213) initiated to evaluate the efficacy and safety of belumosudil (200 mg OD or 200 mg BD) in pts with cGvHD after failure of 2 or more lines of systematic therapy. Trial has a primary completion date of Sept 21. [3,4]
Sep 16PIIa randomised, open-label, 24-week KD025-208 trial (NCT02841995) initiated looking at belumosudil safety at various dose levels (200mg-400mg OD) for the treatment of cGVHD in the US. [3]

Evidence based evaluations