공지 • Jun 11
BeyondSpring Announces Final Positive Data from the PROTECTIVE-1 Phase 3 CIN Program of Plinabulin as a Single Agent Compared to Pegfilgrastim at the American Society of Clinical Oncology (ASCO) Annual Meeting
BeyondSpring Inc. announced presentation of data from the PROTECTIVE-1 Phase 3 clinical study of plinabulin for prevention of chemotherapy-induced neutropenia (CIN) at the American Society of Clinical Oncology (ASCO) Annual Meeting being held on June 4 - 8, 2021. Data further supports plinabulin’s fast onset of action and CIN prevention benefit in week 1 following chemotherapy with results including clinically meaningful endpoints for reduction of febrile neutropenia (FN), hospitalization and bone pain. The Company has submitted New Drug Applications (NDA) for plinabulin in combination with pegfilgrastim for the prevention of CIN, in both the U.S. and China. The U.S. FDA accepted the NDA with Priority Review and assigned a Prescription Drug User Fee Act (PDUFA) action date of November 30, 2021. Plinabulin, BeyondSpring’s lead drug, is a selective immunomodulating microtubule-binding agent (SIMBA). It is a novel, intravenous infused, patent-protected drug that is NDA filed for CIN prevention in the U.S. and China and has a fully enrolled pivotal Phase 3 anti-cancer study for non-small cell lung cancer (NSCLC). Plinabulin triggers the release of the immune defense protein, GEF-H1, which leads to two distinct effects: first is a durable anticancer benefit due to the maturation of dendritic cells resulting in the activation of tumor antigen-specific T-cells to target cancer cells, and the second is early-onset action in CIN prevention after chemotherapy by boosting the number of hematopoietic stem/progenitor cells (HSPCs). Plinabulin received breakthrough designation from both U.S. and China FDA for CIN prevention indication. As a “pipeline in a drug,” plinabulin is being broadly studied in various immuno-oncology regimens to determine if it can boost the effects of the PD-1/PD-L1 antibodies and re-sensitize PD-1/PD-L1 antibody resistant patients. The Plinabulin and G-CSF combination NDA program is comprised of four studies: PROTECTIVE-1 Phase 2 and Phase 3 and PROTECTIVE-2 Phase 2 and Phase 3. PROTECTIVE-1 Phase 2 (4arm randomized study, NSCLC, docetaxel, n=55): Plinabulin single agent (5 mg/m2, 10 mg/m2, or 20 mg/m2, day 1 dose), pegfilgrastim (6 mg, day 2 dose). Plinabulin 20 mg/m2 was selected as the Phase 3 dose. PROTECTIVE-1 Phase 3 (2 arm randomized, double-blind study, NSCLC, breast cancer, prostate cancer, docetaxel, n=105 patients): Plinabulin single agent (40 mg fixed dose – equivalent to 20 mg/m2, day 1 dose) vs. pegfilgrastim (6 mg, day 2 dose). Primary endpoint DSN cycle is met with non-inferiority. Plinabulin showed week 1 early onset of action and was effective in prevention of clinical outcomes, such as FN and hospitalization, and chemo dose reduction and delay. PROTECTIVE-2 Phase 2 (7 arm randomized study, breast cancer, TAC, n=115 patients): Plinabulin single agent (10 mg/m2, 20 mg/m2, or 30 mg/m2, day 1 dose) – 20 mg/m2 selected; Plinabulin (20 mg/m2, day 1 dose) + pegfilgrastim (1.5 mg, 3 mg, or 6 mg, day 2 dose); pegfilgrastim (6 mg, dose 2 dose). Plinabulin (20 mg/m2) and pegfilgrastim (6 mg) was selected to be Phase 3 dose. PROTECTIVE-2 Phase 3 (2 arm randomized, double-blind study, breast cancer, TAC, 221 patients – Pivotal study): Plinabulin (40 mg fixed dose – equivalent to 20 mg/m2, day 1 dose) + pegfilgratstim (6 mg, day 2 dose) vs. pegfilgrastim (6 mg, day 2 dose). The combination is superior to pegfilgrastim alone, which met primary endpoint of prevention of grade 4 neutropenia and key secondary endpoints, with superior benefit in reducing the incidence and severity of febrile neutropenia (FN) and hospitalization, with better quality-of-life (QoL) CIN remains a severely unmet medical need and is the primary cause for the 4D’s (Decrease, Delay, Discontinue dose and Downgrade regimen) that compromise carefully selected cancer treatment regimens. Treatment or prevention of CIN with G-CSF has been the standard of care since Neupogen was approved in 1991. The main benefit of G-CSF treatment, however, is in Week 2 after chemotherapy. Week 1 after chemotherapy is considered the “neutropenia vulnerability gap” where over 75% of CIN-related clinical complications occur, including febrile neutropenia, infection, hospitalization and death. Plinabulin is the first drug seeking FDA approval that has the potential to fill this gap. Combining plinabulin and G-CSF may maximize the protection of patients for the full cycle of chemotherapy, as demonstrated in the PROTECTIVE-2 Phase 3 registration study. Each year in the U.S., 110,000 patients receiving chemotherapy are hospitalized after developing CIN, a severe side effect that increases the risk of infection with fever (also called FN). Due to the COVID-19 pandemic, the updated National Comprehensive Cancer Network (NCCN) guidelines expanded the use of prophylactic G-CSFs, including pegfilgrastim, from high-risk patients only (chemo FN rate >20%), to include intermediate-risk patients (FN rate between 10-20%), to reduce the number of hospital/ER visits related to CIN. The revision of the NCCN guidelines effectively increases the addressable market of patients to approximately 467,500 cancer patients in the U.S. annually.