FDA Grants Belumosudil Priority Review for Chronic GVHD

The FDA has granted a priority review designation to a new drug application for belumosudil for the treatment of patients with chronic graft-versus-host disease.

The FDA has granted a priority review designation to a new drug application (NDA) for belumosudil (KD025) for the treatment of patients with chronic graft-versus-host disease (GVHD).1

The application is based on findings from the pivotal, phase 2 ROCKstar (KDO25-213) trial (NCT03640481), which evaluated belumosudil in patients with chronic GVHD who have received 2 or more prior lines of therapy. Results showed that, in patients who received the agent at a 200-mg once-daily and 200-mg twice-daily dose, the objective response rates (ORRs) were 73% (95% CI, 60%-83%; P < .0001), and 74% (95% CI, 62%-84%; P < .0001), respectively.2

Under the Prescription Drug User Fee Act, the FDA will make a decision on the NDA by May 30, 2021.

"The FDA's acceptance of our NDA for belumosudil represents an important milestone for Kadmon and further highlights the efforts of the Agency to bring meaningful new therapies to cGVHD patients as quickly as possible," said Harlan W. Waksal, MD, president and CEO of Kadmon, the developer of belumosudil. "We look forward to the opportunity to bring belumosudil to market as we continue preparations for a launch, if approved."

The application was submitted under the FDA's Real-Time Oncology Review pilot program, which aims to explore a more efficient review process and certify that safe and effective treatments are available to patients as early as possible, while maintaining and improving review quality.

Additionally, the review of the application is being conducted under FDA Oncology Center of Excellence’s Project Orbis, which is an initiative designed to provide a framework for concurrent submission and review of oncology therapies among participating international partners.

Belumosudil is a selective oral inhibitor of Rho-associated coiled-coil kinase 2 (ROCK2), which is a signaling pathway that modulates inflammatory response and pro-fibrotic processes.

In the ongoing, open-label ROCKstar trial, investigators randomized patients with cGVHD who have received at least 2 prior lines of systemic therapy to receive belumosudil at 200 mg once daily (n = 66) or at 200 mg twice daily (n = 66).

To be eligible for enrollment, patients must be at least 12 years old and have undergone allogenic hematopoietic stem cell transplant, previously received at least 2 lines of systemic therapy, receiving glucocorticoid therapy with a stable dose over the 2 weeks prior to screening, have persistent chronic GVHD manifestations, a Karnofsky performance score of 60 or higher (if aged 16 years or older) or a Lansky performance score of 60 or higher (if aged younger than 16 years), and weigh at least 40 kg.

Those who are not on a stable dose or regimen of systemic chronic GVHD therapy for at least 2 weeks prior to screening, have histological relapse of the underlying disease or posttransplant lymphoproliferative disease at time of screening, and are currently being treated with ibrutinib (Imbruvica) are excluded from enrolling on the trial.

The primary end point is ORR; key secondary endpoints are duration of response, change in Lee Chronic GVHD Symptom Scale Score, response rate by organ system, partial or complete response rate, failure-free survival, overall survival, time to response, and time to next treatment.

Findings also showed that responses occurred in key patient subgroups of patients and were observed by investigators across all organ systems. As of May 2020, the median duration of response has not yet been reached, with 49% of responding patients maintaining their response for at least 20 weeks.

Additional ROCKstar results, which were from a protocol-specified interim analysis, were presented at the 2020 Transplant and Cellular Therapies Meeting.3 The analysis occurred when the last accrued patient had been followed for 2 full months.

Evaluating data by key patient subgroups, trends toward better responses were observed in patients with less severe and shorter duration cGVHD, but the number of involved organ sites failed to indicate a significant difference.

When patients were stratified by prior treatments, there were no statistically significant differences in response based on the number of previous therapies, best response to prior therapy, prior ibrutinib (Imbruvica), or prior ruxolitinib (Jakafi).

At a median duration of follow-up of 5 months, 44 patients in the 200-mg once-daily and 43 in the 200-mg twice-daily dose remained on therapy. Reasons for discontinuation included progression, adverse events (AEs), decision by the investigators, and death.

Regarding safety, the agent was also well tolerated and AEs were consistent with those expected in the patient population.

Any-grade AEs occurred in 95% of the patient population, with 38% and 28% experiencing grade 3/4 and serious AEs, respectively. Drug-related AEs occurred in half of the patients on the study. Five patients died during the study period.

All-grade AEs that occurred in ≥10% of patients included fatigue (24%), diarrhea (21%), nausea (21%), liver-related investigations (20%), peripheral edema (20%), cough (16%), and dyspnea (16%). Grade ≥3 AEs included hypertension in 5% of patients; hyperglycemia and pneumonia in 4% each; and glutathione S-transferase increase, nausea, and vomiting in 3% each.

One-year follow-up data from the ROCKstar trial will be presented at the 2020 ASH Annual Meeting in December.


  1. Kadmon announces FDA acceptance of nda for belumosudil in patients with chronic graft-versus-host disease. News release. Kadom Holdings, Inc. November 30, 2020. Accessed November 30, 2020. https://yhoo.it/3mjcwtr
  2. Kadmon announces positive topline results of pivotal trial of belumosudil (KD025) in chronic graft-versus-host disease. May 21, 2020. Accessed May 21, 2020. https://yhoo.it/2zTLXYu
  3. Cutler CS, Lee S, Arai S, et al. Interim analysis of KD025-213: a phase 2, randomized, multicenter study to evaluate the efficacy and safety of KD025 in subjects with chronic graft versus host disease (cGVHD) after at least 2 prior lines of systemic therapy (The ROCKstar study; NCT03640481). Presented at: 2020 Transplant and Cellular Therapies Meeting; February 19-23, 2020; Orlando, FL. Abstract LBA2.