Antengene Corporation Limited announced that China's National Medical Products Administration (NMPA) has approved a phase II study of selinexor (Xpovio) for the treatment of patients with myelofibrosis (MF).
MF is a clonal bone narrow neoplasm which can emerge either as primary MF (PMF), polycythemia vera (PV) or essential thrombocythemia (ET). The disease is primarily characterized by fibrosis in the bone marrow, extramedullary hematopoiesis, anemia, splenomegaly, constitutional symptoms, and possible progression to leukemia that would shorten patients' survival. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently the only curative treatment for MF. However, such treatment is commonly associated with a high rate of complications and treatment-related deaths. According to the National Comprehensive Cancer Network (NCCN) Guidelines for the Treatment of MF, patients with intermediate-2 or high-risk MF ineligible for allo-HSCT and with a platelet count of =50×109/L should be treated with JAK inhibitors ruxolitinib or fedratinib (2020 NCCN Guidelines). Due to the poor prognosis of patients who have failed or developed resistance to these targeted therapies, MF still represents an urgent unmet medical need.
This randomized, open-label, global multicenter phase II study will be conducted at 15 centers across China, including the primary trial center the First Affiliated Hospital Soochow University, and enroll approximately 20 patients in total. The study is designed to evaluate the safety and efficacy of selinexor versus physician's choice (PC) in patients with MF who had received at least six months of treatment with a JAK1/2 inhibitor. Enrolled patients will be randomized in a 1:1 ratio into one of the two treatment arms, to receive either single agent selinexor or PC treatment. The primary endpoint of the study is the proportion of patients with a =35% spleen volume reduction from baseline (SVR35), as assessed by the independent radiographic review committee (IRC).
Prof. Depei Wu, director of Hematology Department at the First Affiliated Hospital Soochow University, and the principal investigator of the study, noted: “MF is a relatively rare form of proliferative neoplasm in the bone narrow that has long lacked effective treatment options before the emergence of targeted therapies. Allo-HSCT is currently the only curative treatment for patients with MF, yet not all patients with MF are eligible to or tolerant of the treatment. Although ruxolitinib has already been approved in China for the treatment of MF, patients who have failed on or developed resistance to the therapy still have very limited treatment options. This randomized, open-label, global multicenter phase II study is designed to assess the safety and efficacy of selinexor versus physician's choice (PC) in patients with MF who had received at least six months of treatment with a JAK1/2 inhibitor. We are very hopeful that this study will provide additional evidence supporting the exploration of effective treatments for MF and ultimately provide a new treatment option to patients with MF in China.”
Dr. Jay Mei, founder, chairman and CEO of Antengene, commented: “The NMPA's approval for this clinical trial of selinexor in patients with MF marks another major milestone in our effort in developing selinexor in a broad range of diseases, and a big step towards expanding potential indications for this candidate drug. We are confident that selinexor will demonstrate its clinical utility in the treatment of MF as we progress with this clinical development program. We look forward to advancing this study under the oversight of the NMPA, and aim to achieve a clinical breakthrough for patients with MF in China.”
Selinexor is a first-in-class oral selective inhibitor of nuclear export (SINE) compound discovered and developed by Karyopharm Therapeutics, Selinexor is currently being developed by Antengene, which has the exclusive development and commercial rights in certain Asia-Pacific markets, including Greater China, Korea, Australia, New Zealand and the ASEAN countries, and already obtained an NDA approval in South Korea through a priority review process.
Selinexor is so far the first and only oral SINE compound approved by the FDA and is the first drug approved for the treatment of both MM and DLBCL. Selinexor is also being evaluated in several other mid-and later-phase clinical trials across multiple solid tumor indications, including liposarcoma and endometrial cancer.