Antengene Corporation Limited today announced that the U.S. Food and Drug Administration (FDA) has approved the supplemental New Drug Application (sNDA) submitted by its partner Karyopharm Therapeutics Inc. for oral XPOVIO? (selinexor, ATG-010), a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) medicine, in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. This indication was approved three months ahead of its March Prescription Drug User Fee Act (PDUFA) date based on the result of a confirmatory Phase 3 BOSTON study.

XPOVIO? was previously approved under the FDA's Accelerated Approval Program for the treatment of adult patients with relapsed or refractory multiple myeloma (rrMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody.

XPOVIO?, a first-in-class and only-in-class oral SINE compound, and now the first and only drug approved by FDA for use in both multiple myeloma and diffuse large B-cell lymphoma, discovered and developed by Karyopharm, is currently being developed by Antengene, who has the exclusive development and commercial rights in certain Asia-Pacific markets, including China. In December 2020, National Comprehensive Cancer Network (NCCN?) added three different XPOVIO? combination regimens to its Clinical Practice Guidelines in Oncology (NCCN? Guidelines) for previously treated multiple myeloma.

Antengene has conducted two Phase 2 registrational clinical trials of XPOVIO? in China for relapsed or refractory multiple myeloma (MARCH) and for relapsed or refractory diffuse large B-cell lymphoma (SEARCH). A Phase 3 randomized, controlled, open-label and multicenter BENCH trial has also received the IND approval from the National Medical Products Administration (NMPA) in China. Antengene is working on making XPOVIO? commercially available in Asia Pacific regions and has submitted the New Drug Applications (NDAs) for XPOVIO? to the Health Sciences Authority (HSA) of Singapore and the Australian Therapeutic Goods Administration (TGA) for three indications, including the treatment of patients with multiple myeloma who have received at least one prior therapy.

 "This is the third approved indication for XPOVIO?, highlighting its potential of clinical application and broad market prospects. XPOVIO? offers patients with rrMM and their physicians the first oral SINE compound and makes more treatment options available to cancer patients with critical unmet medical needs." Dr. Jay Mei, M.D., Ph.D., Founder, Chairman and CEO of Antengene said, "We plan to launch XPOVIO? as soon as possible for the treatment of patients with rrMM and rrDLBCL in APAC following regulatory approvals, by leveraging our established commercial infrastructure and seasoned international team."

About the Phase 3 BOSTON Study

The approval of XPOVIO? in combination with once-weekly bortezomib plus low-dose dexamethasone (SVd) is supported by the results of the multi-center, Phase 3, randomized study, which evaluated 402 adult patients with relapsed or refractory multiple myeloma who had received one to three prior lines of therapy. The study was designed to compare the efficacy, safety and certain health-related quality of life parameters of once-weekly XPOVIO? (selinexor) in combination with once-weekly bortezomib plus low-dose dexamethasone (SVd) versus twice-weekly bortezomib plus dexamethasone (Vd). The primary endpoint of the study was progression-free survival (PFS) and key secondary endpoints included overall response rate (ORR), rate of peripheral neuropathy, and others. Additionally, the BOSTON study allowed for patients on the Vd control arm to crossover to the SVd arm following objective (quantitative) progression of disease verified by an Independent Review Committee (IRC). The BOSTON study was conducted at over 150 clinical sites internationally.

Although the study had one of the highest proportions of patients with high-risk cytogenetics (~50%) as compared with other bortezomib-based studies in previously treated myeloma, the median PFS in the SVd arm was 13.9 months compared to 9.5 months in the Vd arm, representing a 4.4 month increase in median PFS (hazard ratio [HR] of 0.70; p=0.0075). The SVd group also demonstrated a significantly greater ORR compared to the Vd group (76.4% vs. 62.3%, p=0.0012). Importantly, SVd therapy compared to Vd therapy showed consistent PFS benefit and higher ORR across several important subgroups.

In addition, the following results favored SVd therapy as compared to Vd therapy:

• SVd therapy demonstrated a significantly higher rate of deep responses, defined as ≥ Very Good Partial Response compared to Vd therapy (44.6% vs. 32.4%) as well as a longer median duration of response (20.3 months vs. 12.9 months). Additionally, 17% of patients on the SVd arm achieved a Complete Response or a Stringent Complete Response as compared to 10% of patients receiving Vd therapy. All responses were confirmed by an IRC.
  

• Peripheral neuropathy (PN) rates were significantly lower on SVd compared to Vd (32% vs. 47%). In addition, PN rates ≥ Grade 2 were also significantly lower in the SVd arm compared to Vd (21% vs. 34%).

The most common adverse reactions were cytopenias, along with gastrointestinal and constitutional symptoms and were consistent with those previously reported from other selinexor studies. Most adverse reactions were manageable with dose modifications and/or standard supportive care. The most common non-hematologic adverse reactions were nausea (50%), fatigue (42%), decreased appetite (35%), and diarrhea (32%) and were mostly Grade 1 and 2 events. The most common Grade 3 and 4 adverse reactions were thrombocytopenia (43%), lymphopenia (38%), anemia (17%), and fatigue (13%). 

About XPOVIO? (selinexor, ATG-010)

XPOVIO? (selinexor, ATG-010), a first-in-class and only-in-class oral selective inhibitor of nuclear export compound discovered and developed by Karyopharm, is currently being developed by Antengene, who has the exclusive development and commercial rights in certain Asia-Pacific markets, including China. In July 2019, the US Food and Drug Administration (FDA) approved Selinexor (XPOVIO?) in combination with low-dose dexamethasone for the treatment of relapsed/refractory multiple myeloma (rrMM) and in June 2020 approved selinexor (XPOVIO?) as a single-agent for the treatment of relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL). A Marketing Authorization Application (MAA) has also been submitted to the European Medicines Agency (EMA) with a request for conditional approval of selinexor (XPOVIO?) in this same rrMM indication. On December 18, 2020, the supplemental New Drug Application (sNDA) requesting an expansion of its indication to include the treatment for patients with multiple myeloma after at least one prior therapy was approved by the FDA. Selinexor (XPOVIO?) is so far the first and only oral SINE compound approved by the FDA. Selinexor (XPOVIO?) 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 3 randomized, double blind, placebo controlled, cross-over SEAL study evaluating single agent, oral selinexor (XPOVIO?) versus matching placebo in patients with liposarcoma. Karyopharm also recently announced that the ongoing Phase 3 SIENDO study of selinexor (XPOVIO?) in patients with endometrial cancer passed planned interim futility analysis and that Data and Safety Monitoring Board (DSMB) recommended the study should proceed as planned without any modifications. Top-line SIENDO study results are expected in the second half of 2021.

Antengene is conducting two registrational Phase 2 clinical trials of selinexor (XPOVIO?) in China for relapsed refractory multiple myeloma (MARCH) and for relapsed refractory diffuse large B-cell lymphoma (SEARCH), and has initiated clinical trials for high prevalence cancer types in the Asia Pacific region including peripheral T-cell lymphoma and NK/T-cell lymphoma (TOUCH) and KRAS-mutant non-small cell lung cancer (TRUMP).

About Antengene

Antengene Corporation Limited ("Antengene", SEHK: 6996.HK) is a leading clinical-stage Asia-Pacific biopharmaceutical company focused on innovative oncology medicines. Antengene aims to provide the most advanced anti-cancer drugs to patients in China, the Asia Pacific Region and around the world. Since its establishment, Antengene has built a pipeline of 12 clinical and pre-clinical stage assets and obtained 11 investigational new drug approvals in Asia Pacific. The vision of Antengene is to "Treat Patients Beyond Borders". Antengene aims to address significant unmet medical needs by discovering, developing and commercializing first-in-class/best-in-class therapeutics.