The FDA has extended the review period for the new drug application for belumosudil for use in patients with chronic graft-versus-host disease to allow for more time to review additional data submitted by the biopharmaceutical company.
The FDA has extended the review period for the new drug application (NDA) for belumosudil (KD025) for use in patients with chronic graft-versus-host disease (GVHD) to allow for more time to review additional data submitted by the biopharmaceutical company.1
Kadmon Holdings, Inc., the drug developer, submitted the information to address a request issued by the regulatory agency. The information has been determined by the FDA to represent a major amendment to the application, which led to an extension of the Prescription Drug User Fee Act by 3 months.
The new date for the agency to make a decision on the NDA is August 30, 2021.
The application was based on data from the phase 2 ROCKstar (KDO25-213) trial (NCT03640481), which examined the agent in patients with chronic GVHD who previously 2 or more lines of therapy. The objective response rate (ORR) in patients who were given belumosudil at a once-daily dose of 200 mg was 73% (95% CI, 60%-83%; P <.0001).2 The ORR was slightly higher in patients who received the agent at a twice-daily dose of 200 mg, at 74% (95% CI, 62%-84%; P <.0001).
“We remain confident in the data supporting our application for belumosudil in chronic GVHD and look forward to continuing to work closely with the FDA during the remainder of the review process,” Harlan W. Waksal, MD, president and chief executive officer of Kadmon, stated in a press release. “We are committed to bringing belumosudil to market, once approved, to help meet the needs of patients living with GVHD.”
In the open-label ROCKstar trial, patients with GVHD who had previously received at least 2 lines of systemic treatment were randomized to receive either belumosudil at a once-daily dose of 200 mg (n = 66) or a twice-daily dose of 200 mg (n = 66).
Patients had to be at least 12 years of age and have undergone allogenic hematopoietic stem cell transplant to participate. Moreover, patients also had to have received 2 prior lines of systemic therapy, have received glucocorticoid therapy with a stable dose over the 2 weeks before screening, have persistent chronic GVHD manifestations. Eligible patients also had to have a Karnofsky performance score of 60 or higher (if 16 years of age or older) or a Lansky performance score of 60 or higher (if younger than 16 years) and weigh at least 40 kg.
Patients who were not on a stable dose or regimen of systemic chronic GVHD therapy for at least 2 weeks before screening and who had histological relapse of underlying disease or posttransplant lymphoproliferative disease at time of screening were excluded. Additionally, patients who were receiving ibrutinib (Imbruvica) were not permitted.
The primary end point of the trial was ORR, while secondary end points comprised duration of response (DOR), 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.
Additional data from the trial showed that belumosudil elicited responses in key patient subgroups analyzed and across all organ systems. The median DOR with the agent had not yet been reached as of May 2020. Moreover, 49% of patients continued to experience a response to treatment for at least 20 weeks.
Data from the protocol-specific interim analysis of the trial were revealed during the 2020 Transplant and Cellular Therapies Meeting.3 Here, trends toward better responses with the agent were observed in patients with less severe and shorter duration chronic GVHD; however, the number of involved organ sites did not indicate a significance difference with treatment.
Moreover, when participants were stratified by previous treatments received, no statistically significant differences in response to belumosudil were observed based on the number of prior therapies, best response to previous therapy, prior ibrutinib, or previous ruxolitinib (Jakafi).
At a median duration of 5 months of follow-up, a total of 44 patients receiving the once-daily dose of the agent and 43 patients receiving the twice-daily dose continued to receive treatment. Patients discontinued belumosudil because of disease progression, toxicities, investigator decision, as well as death.
Ninety-five percent of patients experienced any-grade adverse effects (AEs) with belumosudil; 38% of patients had grade 3/4 toxicities with the agent, while 28% reported serious AEs. Fifty percent of the patients had toxicities that were determined to be associated with the study drug. A total of 5 patients died during the study period.
Fatigue was reported in 24% of patients, followed by diarrhea in 21%, nausea in 21%, liver-related investigations in 20%, peripheral edema in 20%, cough in 16%, and dyspnea in 16%. Grade 3 or higher toxicities included hypertension, which occurred in 5% of participants, along with hyperglycemia and pneumonia (4% each), glutathione S-transferase increase (3%), nausea (3%), and vomiting (3%).