Positive Responses With Belumosudil in GVHD Spark Pending FDA Submission

Patients with chronic graft-versus-host-disease (GVHD) who received belumosudil (KD025) had clinically meaningful responses to treatment with belumosudil in the pivotal phase II ROCKstar (KD025-213) trial, according to top-line results announced by Kadmon Holdings, Inc.¹

Based on these primary analysis results, a New Drug Application is underway for submission to the FDA in the Real-Time oncology Review pilot program by the fourth quarter of 2020.

"Treatment with belumosudil has demonstrated compelling results for this major unmet medical need. Importantly, belumosudil has been very well tolerated, which allows trial participants to stay on therapy and achieve meaningful responses," said Madan Jagasia, MD, MS, MMHC, professor of Medicine, Vanderbilt University Medical Center. “These results demonstrate the potential of belumosudil to become a cornerstone of the cGVHD treatment paradigm if approved, as it delivers meaningful and sustained benefits to patients with this serious condition."

Belumosudil was administered on 2 different dosing schedules in the study, 200 mg once daily and 200 mg twice daily. The overall response rate (ORR) achieved with the once-daily dose was 73% (95% CI, 50%-83%; P <.0001). With the twice-daily dose of belumosudil, the ORR was 74% (95% CI, 62%-84%; P <.001). Treatment responses were observed across the various subgroups in the study.

In terms of durability, responses were maintained in 49% of patients for 20 weeks or more, at the time of the primary analysis. These data continue to mature, and the median duration of response has not yet been reached.

Overall, treatment with belumosudil was well-tolerated, and adverse events were consistent with prior reports. There were no occurrences of cytomegalovirus infection reactivation or drug-related cytopenias.

Results seen in the primary analysis are a slight improvement from the interim analysis results announced in February of 2020. At that time, the ORR was 64% (95% CI, 51%-75%, P <.0001) in patients who received the 200 mg once-daily dose of the drug and 67% (95% CI, 54%-78%; P <.0001) for the twice-daily group. The interim subgroup analysis showed responses across subgroups as well. In patients who had 4 or more organs affected by their disease, the ORR was 64%, in patients previously treated with ibrutinib (Imbruvica), the ORR was 62%, and in those who received prior ruxolitinib (Jakafi), the ORR was also 62%. Additionally, 3 patients achieved a complete response.²

The open-label, randomized, multicenter ROCKstar trial accrued patients aged 12 years and older with chronic GVHD who have undergone allogeneic hematopoietic cell transplant, received 2 to 5 prior line of systemic therapy, who were receiving a stable dose of glucocorticoid therapy for 2 weeks prior to screening, a Karnofsky Performance Score of ≥ 60, and a weight of at least 40 kg. Patients with histological relapse of underlying cancer or post-transplant lymphoproliferative disease at screening, and those who were presently receiving ibrutinib (Imbruvica), were excluded from the study.

"The remarkable results achieved with belumosudil in this advanced patient population demonstrate its broad potential to offer meaningful clinical benefit to cGVHD patients," said Sanjay K. Aggarwal, MD, senior vice president, Clinical Development of Kadmon. "We look forward to sharing the full dataset from the ROCKstar study at an upcoming medical meeting.¹"

_References:

_{Kadmon announces positive topline results of pivotal trial of belumosudil (kd025) in chronic graft-versus-host disease [news release]. New York, NY: Kadmon Holding, Inc; May 21, 2020. https://bit.ly/3bRlqse. Accessed May 21, 2020.}

_{Kadmon announces expanded results of interim analysis of pivotal trial of kd025 in cgvhd [news release]. New York, NY: Kadmon Holding, Inc; February 23, 2020. https://bit.ly/2Zoc3gY. Accessed May 21, 2020.}