On August 23, 2021 Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative biopharmaceutical company dedicated to discovering, developing and commercializing global first-in-class and/or best-in-class therapeutics in hematology and oncology, reported that China’s National Medical Products Administration has approved a Phase II study of selinexor (XPOVIO) for the treatment of patients with myelofibrosis (MF) (Press release, Antengene, AUG 23, 2021, View Source [SID1234586822]).
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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."
About Selinexor (XPOVIO)
Selinexor is a first-in-class oral selective inhibitor of nuclear export (SINE) compound discovered and developed by Karyopharm Therapeutics Inc. (NASDAQ: KPTI), 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.
In July 2019, the US Food and Drug Administration (FDA) approved selinexor in combination with low-dose dexamethasone for the treatment of relapsed/refractory multiple myeloma (RRMM) and in June 2020 approved selinexor as a single-agent for the treatment of relapsed/refractory diffuse large B-cell lymphoma (RR DLBCL). In December 2020, selinexor also received FDA approval as a combination treatment for multiple myeloma after at least one prior therapy. In February 2021, selinexor was approved by the Israeli Ministry of Health for the treatment of patients with RRMM or RR DLBCL and in March 2021, the European Commission (EC) has granted conditional marketing authorization for selinexor (NEXPOVIO) for the treatment of adult patients with RRMM.
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. In November 2020, at the Connective Tissue Oncology Society 2020 Annual Meeting (CTOS 2020), Antengene’s partner, Karyopharm, presented positive results from the Phase III randomized, double blind, placebo controlled, cross-over SEAL trial evaluating single agent, oral selinexor versus matching placebo in patients with liposarcoma. Karyopharm also announced that the ongoing Phase III SIENDO trial of selinexor in patients with endometrial cancer passed the planned interim futility analysis and the Data and Safety Monitoring Board (DSMB) recommended the trial should proceed as planned without any modifications. Top-line SIENDO trial results are expected in the second half of 2021.
Antengene is currently conducting multiple clinical trials of selinexor for the treatment of MM, DLBCL, endometrial cancer, and peripheral T and NK/T-cell lymphoma, and five of these trials are at late-stages (Phase II/III).