The FDA accepted the New Drug Application from belumosudil and granted it a Priority Review designation for the treatment of patients with chronic graft-versus-host disease. The Prescription Drug User Fee Act target action date has been set to May 30, 2021.
The FDA accepted the New Drug Application (NDA) from belumosudil (KD025) and granted it a Priority Review designation for the treatment of patients with chronic graft-versus-host disease (GVHD). The Prescription Drug User Fee Act target action date has been set to May 30, 2021.1
The NDA submission is supported by positive data from phase 2 KD025-213 clinical trial of belumosudil administered to patients with chronic GVHD after at least 2 prior lines of systemic therapy.
"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 [chronic] GVHD patients as quickly as possible," said Harlan W. Waksal, MD, president and chief executive office, Kadmon Holdings, Inc., in a statement.
Interim findings from the KD025-213 study were presented during the 2020 Transplantation & Cellular Therapy (TCT) Meetings in February 2020. The results showed that the Rho-associated coiled-coil kinase 2 inhibitor achieved a clinically meaningful objective response rate (ORR) in patients with chronic GVHD, showing consistency will prior research.2
The patient population was compiled of 132 patients who were previously treated with 2 to 5 prior therapies. Patients were randomized 1:1 to receive either belumosudil 200 mg once daily (QD) or 200 mg twice daily (BID). All patients in the study received treatment until clinically significant progression or unacceptable toxicity. The ORR defined by the 2014 National Institute of Health Consensus Development Project on clinical trials in chronic GVHD was the primary end point of the study. Duration of response, Lee Symptom Scale score, corticosteroid reductions, failure-free survival, and overall were also evaluated as secondary end points.
At baseline, the median age of the overall patients population was 56 years (range, 21-77). The population was 57% male. Patients had a median of 4 prior lines of therapy and notably, 34% had received prior ibrutinib (Imbruvica). Patients had a 28-month median time to chronic GVHD diagnosis. In 66% of the patients enrolled the chronic GVHD was considered severe. Four or more organs were involved in the chronic GVHD for 52% of the study population. The patients also had a median prednisone dose of 0.2 mg and 73% were refractory to their prior therapy.
In the cohort of patient who received a QD dose of belumosudil, the ORR was 64% compared with 67% in the BID group. Complete responses were observed in 3 patients. It was also noted that the positive ORR results were seen in across the subgroup population assessed.
Although adverse events (AEs) were observed in >15% of the study population, belumosudil was well-tolerated overall. At the time of the interim analysis, safety data were available for 67% of the QD group and 65% of the BID group. The AEs seen in the QD and BID arms included fatigue (30%, 18%), diarrhea (24%, 18%), nausea (23%, 20%), liver related investigations (20%, 23%), edema (24%, 15%), cough (18, 14%) dyspnea (20%, 12%), respectively. Serious AEs occurred in >2% of patients and included pneumonia (3%, 3%), nausea (3%, 2%), pyrexia (5%, 0) and vomiting (3%, 2%) in the QD and BID arms, respectively.
Five deaths occurred during the study, but 4 of them were not related to treatment with belumosudil.
The study of belumosudil is ongoing and currently recruiting patients. To be eligible for enrollment, individuals are required to be previously treated with 2 to 5 lines of therapy, be receiving glucocorticoid therapy with a stable dose over the 2 weeks before study screening, have persistent chronic GVHD, have a Karnofsky Performance Score of ≥ 60 if 16 years of age or older, have a Lansky Performance Score of ≥ 60, and meet the weight requirement of at least 40kg.
With a Priority Review designation, the NDA for belumosudil will be reviewed over a period of 6 months. It will also be reviewed as part of the FDA's Real-Time Oncology Review pilot program, which is a more efficient review process. A review of the NDA for belumosudil as treatment of chronic GVHD will also be examined under Project Orbis, an initiative of the FDA Oncology Center of Excellence.
Belumosudil has previously received Breakthrough Therapy Designation as well as Orphan drug designation for the treatment of patients with chronic GVHD. While under FDA review, updated data from the phase 2 KD025-213 study during the 2020 American Society of Hematology Annual Meeting.
1. Kadmon [DT1] announces FDA acceptance of NDA for belumosudil in patients with chronic graft-versus-host disease. News release. Kadmon Holdings, Inc. November 30, 2020. Accessed November 30, 2020. https://yhoo.it/3fToxTP
2. Cutler C, Arai S, Zoghi B, 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 Transplantation & Cellular Therapy Meetings; February 19-23, 2020. Orlando, FL. Abstract LBA2.