Debiopharma Announces FDA Approval of First-in-Class XPO1 Inhibitor Selinexor (ATG-010) for Relapsed/Refractory Multiple Myeloma

VCBeat (WeChat ID: biobeat1) has learned that ANTENGENE CORPORATION, an innovative pharmaceutical company focused on oncology, and its partner Karyopharm Therapeutics Inc. (hereinafter referred to as “Karyopharm,” Nasdaq: KPTI) announced that the U.S. Food and Drug Administration (FDA) has officially approved XPOVIO, the world’s first nuclear export inhibitor developed through their collaboration.^TM(Selinexor, product code ATG-010 of Antengene Corporation) in combination with low-dose dexamethasone for the treatment of relapsed/refractory multiple myeloma (RRMM). These patients had received at least multiple prior lines of therapy, including proteasome inhibitors, immunomodulatory drugs, and CD38 monoclonal antibodies.

Furthermore, the Phase III clinical trial (BOSTON) evaluating selinexor in combination with bortezomib and low-dose dexamethasone for the treatment of relapsed/refractory multiple myeloma has completed patient enrollment. The FDA’s accelerated approval has provided patients with relapsed/refractory multiple myeloma an innovative drug with a mechanism of action entirely distinct from that of existing clinical therapies.

Dr. Sundar Jagannath, Director of the Multiple Myeloma Program at Mount Sinai School of Medicine, Professor of Hematology and Medical Oncology, and Principal Investigator of the STORM clinical trial, stated: “In the pivotal Phase 2b STORM clinical trial, the overall response rate of 25.3% observed in the subgroup of 83 patients was clinically meaningful. This overall response rate also serves as XPOVIO”^TM“...forms the basis for FDA accelerated approval and indicates that patients will derive clinical benefit.”

Dr. Paul Richardson, Clinical Program Director and Center Director of the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute, stated: “Despite recent advances in the treatment of multiple myeloma, nearly all of our patients develop resistance to the five most commonly used anti-myeloma agents currently available, and this patient population has a particularly poor prognosis. Oral XPOVIO^TMThe accelerated approval marks selinexor as an exciting new treatment option for patients with relapsed or refractory disease who have exhausted all existing therapies.”

Dr. Mei Jianming, Founder, Chairman and CEO of Antengene Corporation, stated: “XPOVIO^TMThe approval of selinexor for marketing in the United States is highly encouraging. For patients with relapsed/refractory multiple myeloma in China, there is an equally urgent need for innovative therapies with novel mechanisms of action. In response to the pressing needs of Chinese patients, we feel a profound sense of responsibility and urgency. The clinical trial of selinexor (ATG-010) for the treatment of advanced relapsed/refractory multiple myeloma in China has received approval from regulatory authorities, and patient enrollment and treatment are expected to commence this August. Furthermore, we will continue to investigate selinexor for the treatment of various other hematologic malignancies and solid tumors, including diffuse large B-cell lymphoma, T-cell lymphoma, endometrial cancer, and glioma. We look forward to making this innovative therapy available to patients in China as soon as possible.

Dr. Sharon Shacham, Founder, President, and Chief Scientific Officer of Karyopharm Therapeutics, a partner of ANTENGENE CORPORATION, stated: “With today’s XPOVIO^TM"Having received accelerated approval from the FDA, patients with relapsed or refractory multiple myeloma now have a brand-new treatment option." She also stated, "Developing a drug such as XPOVIO^TMBringing an innovative drug with a novel mechanism of action to market and securing FDA approval requires the concerted efforts and dedication of many individuals, including patients, family members, caregivers, and physicians who participated in our clinical trials. We are deeply grateful for everyone’s contributions to this significant milestone and look forward to achieving even greater breakthroughs in our ongoing commitment to improving the quality of life for cancer patients.

On May 29, 2018, Antengene Corporation and Karyopharm signed a strategic cooperation agreement in Shanghai to jointly develop products including ATG-010 (XPOVIO^TM, selinexor), four oral innovative drugs in clinical development. Following the initiation of the collaboration, ATG-010 received clinical trial approval from China’s National Medical Products Administration on January 28, 2019, and is scheduled to commence clinical trials this August. It is reported that, in addition to continuously advancing the development of ATG-010 for indications beyond multiple myeloma, Antengene Corporation is building its commercialization team and actively preparing for the market launch of selinexor and subsequent products.

XPOVIO^TMXPOVIO is a first-in-class, oral, selective inhibitor of nuclear export (SINE) that functions by binding to and inhibiting the nuclear export protein XPO1 (also known as CRM1). This mechanism leads to the accumulation of tumor suppressor proteins within the nucleus, thereby reactivating and amplifying their tumor-suppressive functions, inducing apoptosis in cancer cells while largely sparing normal cells from damage.^TMIn addition to the FDA’s accelerated approval in July 2019 for the indication of relapsed or refractory multiple myeloma after failure of treatment with bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab, a Marketing Authorization Application (MAA) has also been submitted to the European Medicines Agency (EMA).

Meanwhile, selinexor is also undergoing clinical studies for the indication of relapsed or refractory diffuse large B-cell lymphoma (DLBCL). In 2018, Karyopharm reported the results from the Phase 2b SADAL trial in patients with DLBCL who had experienced relapse or were refractory after at least two prior lines of therapy, and the drug has been granted Fast Track designation by the FDA.

Furthermore, selinexor is currently undergoing multiple mid- and late-stage clinical trials for various cancer indications, including the Phase III BOSTON trial evaluating its combination with bortezomib and low-dose dexamethasone for the treatment of multiple myeloma; the STOMP trial, which assesses selinexor as a potential backbone therapy in combination with other approved multiple myeloma agents; as well as several other clinical studies such as SEAL for liposarcoma, KING for recurrent glioma, and SIENDO for endometrial cancer.

ANTENGENE CORPORATION is an innovative pharmaceutical company focused on new drug development, clinical research, and commercialization. It is dedicated to addressing unmet medical needs in Asia and strives to provide patients in China and the Asia-Pacific region with cutting-edge, leading innovative therapies in oncology and antiviral treatment. In April 2017, Celgene Corporation (NASDAQ: CELG), a global leader in innovative medicines, became a long-term strategic partner of ANTENGENE CORPORATION and invested in the company.

Currently, Antengene Corporation has five products in clinical development and marketed stages: XPOVIO^TM(selinexor, ATG-010) is a therapeutic product for relapsed/refractory multiple myeloma (MM) that has been approved for marketing in the United States. Clinical studies evaluating its use in diffuse large B-cell lymphoma (DLBCL) and various other solid tumors are currently in Phase II/III trials. ATG-008 is being investigated in multi-center clinical trials for hepatocellular carcinoma across several Asia-Pacific regions, including mainland China, Taiwan, and South Korea. ATG-016 and ATG-019 are investigational oncology products targeting novel mechanisms and targets, currently in Phase I/II clinical development for the treatment of various cancers, including myelodysplastic syndrome (MDS), colorectal cancer, and prostate cancer. ATG-527 is an investigational antiviral agent currently undergoing clinical evaluation for the treatment of influenza, respiratory syncytial virus (RSV), and Epstein-Barr virus (EBV) infections, having completed its Phase I clinical trial.

Karyopharm Therapeutics Inc. (NASDAQ: KPTI) is a company focused on the research, development, and commercialization of novel nuclear export inhibitors with new mechanisms of action and novel targets for the treatment of cancer and other diseases. Its investigational Selective Inhibitor of Nuclear Export (SINE) compounds function by binding to and inhibiting the nuclear export protein XPO1 (also known as CRM1). The company’s first product, XPOVIO™ (selinexor), received accelerated approval from the U.S. FDA on July 3, 2019, in combination with low-dose dexamethasone, for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM).

The Marketing Authorization Application (MAA) for the product in Europe is also under review by the European Medicines Agency (EMA). In addition to treating various tumors as monotherapy and in combination regimens, the Company’s SINE compounds have demonstrated biological activity in a range of other conditions, including neurodegenerative diseases, inflammation, autoimmune disorders, and viral infections. The Company currently has multiple research projects in clinical or preclinical development.