Breakthrough drug for chronic graft anti-host disease (cGVHD)! ROCK2 inhibitor belumosudil U.S. entry review: total mitigation rate > 70%

December 04, 2020 // -- Kadmon Holdings recently announced that the U.S. Food and Drug Administration (FDA) has accepted a new drug application (NDA) from Belumosudil (KD025), an oral selective Rho-associated coil protein kinase 2 (ROCK2) inhibitor used to treat patients with chronic graft anti-host disease (cGVHD).
FDA has granted priority review to the NDA and has designated a target date for the Prescription Drug User Charge Act (PDUFA) as May 30, 2021.
the NDA will be reviewed under the FDA's Real-Time Oncology Review (RTOR) and Orbis pilot projects.
submitted Belumosudil's NDA under the FDA's Real-Time Oncology Review (RTOR) pilot program.
the pilot program aims to explore more effective review processes to ensure patients receive safe and effective treatment as early as possible, while maintaining and improving the quality of the review.
review of the Belumosudil NDA will also be conducted under the FDA's Orbis program, an initiative of the FDA's Center of Excellence for Oncology.
Oribs project provides a framework for the submission and review of cancer products among international partners.
cGVHD is a common fatal complication after hematopoietic stem cell transplantation.
In cGVHD, transplanted immune cells (transplants) attack the patient's cells (hosts), causing inflammation and fibrosis in multiple tissues such as the skin, mouth, eyes, joints, liver, lungs, esovirus and gastrointestinal tract.
, there are currently about 14,000 cases of cGVHD in the United States, with about 5,000 new cases each year.
belosudil is the selected oral inhibitor of Rho-associated curling protein kinase 2 (ROCK2), a signaling pathway that regulates the immune response and fibrosis pathways.
belumosudil inhibits ROCK2 signaling path, lowers inflammatory Th17 cells, increases regulatory T(Treg) cells, rebalances the immune response, and treats immunodeficirative disorders.
addition to cGVHD, belumosudil is conducting a Phase II clinical trial of adult diffuse skin systemic sclerosis (KD025-209).
previously, belumosudil was awarded breakthrough drug eligibility (BTD) and orphan drug eligibility (ODD) by the U.S. Food and Drug Administration (FDA) for the treatment of cGVHD patients who had previously received at least two systemic treatments.
the chemical structure and mechanism of action of beloumosudil (KD025) NDA was supported by positive results from key clinical trials ROCKstar (KD025-213, NCT03640481).
is a randomized, multi-center, open-label Phase II study conducted in adult and adolescent patients with cGVHD who had previously received at least two system therapies.
study, patients were randomly assigned to 2 groups of patients who received 200 mg (200 mg QD) per day and 2 200 mg (200 mg BID) per day for 66 patients in each group.
study, statistically significant if the lower limit of 95% CI of the total mitigation rate (ORR) exceeded 30%.
previously published results showed that the study had reached the END of ORR in an interim analysis conducted two months after the patient was admitted to the group (October 2019).
data show that the ORR of KD025 200mg QD group and 200mg BID group is 64% (95% CI:51%, 75%, p<0.0001), 67% (95% CI:54%, 78%, p<0001), respectively, and the data are statistically and clinically significant.
positive top line results released in May this year showed that in the main analysis conducted six months after the completion of the patient's entry into the group, the ORR in the KD025 200mg QD group and the 200mg BID group were 73% (95% CI: 60%, 83%, p<0.0001), 74% (95% CI: 62%, 84%, p<0.0001), the data are clinically and statistically significant.
, treatment remission was observed in all key patient subgroups and complete remission was observed in all affected organ systems, including organs with fibrosis disease.
studies, belumosudil was well-to-do and adverse reactions were consistent with expectations in the patient population.
no infection or reactivation of the cytocytovirus (CMV) or a significant decrease in drug-related cells were found.
12-month data from the study will be presented orally at the 62nd annual meeting of the American Society of Hematology (ASH) on December 6, 2020.
CGVHD is an area with significant unsealed medical needs, and Belumosudil has shown convincing results in treating late-stage CVHD," said Madan Jagasia, chief medical officer of Vanderbilt Cancer Center (VICC), an investigator for the KD025-208 and ROCKstar studies, and chairman of the ROCKstar Steering Committee.
, belumosudil's tolerance is very good, which allows the participants to stick to the treatment and get meaningful therapeutic relief.
these results suggest that, if approved, belumosudil has the potential to be the cornerstone of the cGVHD treatment model, bringing meaningful and ongoing benefits to patients with this serious disease.
Origin: Kadmon Announces FDA Acceptance of NDA for Belumosudil in Patients With Chronic Graft-Versus-Host Disease