– Data further supports plinabulin’s fast onset of action and CIN prevention benefit in week 1 following chemotherapy
– Single agent plinabulin (day 1 dose as chemotherapy), had non-inferior protection against CIN compared to pegfilgrastim (day 2 dose), while performing numerically better for reduction of febrile neutropenia and chemo dose delay, with significantly lower bone pain
NEW YORK, June 10, 2021 – BeyondSpring Inc. (the “Company” or “BeyondSpring”) (NASDAQ: BYSI), a global biopharmaceutical company focused on the development of innovative cancer therapies, today 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.
The poster titled “Head-to-Head Comparison of Single Agent (SA) Plinabulin (Plin) versus Pegfilgrastim (Peg) for the Prevention of Chemotherapy-Induced Neutropenia (CIN) in the Phase 3 Trial PROTECTIVE-1,” was presented at 9:00 a.m. ET on June 4, 2021, at Lung Cancer Poster Session (Abstract #547) is the PROTECTIVE-1 Phase 3 data comparing plinabulin versus pegfilgrastim. 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.
- Primary endpoint of demonstrating non-inferiority of single agent plinabulin versus single agent pegfilgrastim was met: DSN (days of severe neutropenia) cycle 1, non-inferiority margin of 0.65 day criterion between plinabulin and pegfilgrastim was met.
- Comparable or numerically better clinical sequelae of CIN for plinabulin vs. pegfilgrastim:
|Hospitalization||Docetaxel Discontinue||Docetaxel Delay|
- Significant improvement in bone pain and platelet count: Less bone pain (p=0.01) and less thrombocytopenia (p<0.0001 on D15) compared to pegfilgrastim.
- Same day convenience of use: Plinabulin is infused on the same day (Day 1) as chemotherapy, 30 minutes after chemotherapy with 30 minutes of intravenous infusion, whereas pegfilgrastim on the next day (Day 2).
“The dedicated program of plinabulin in CIN prevention was comprised of four studies to show the unique profile of plinabulin: PROTECTIVE-1 Phase 2 and Phase 3 and PROTECTIVE-2 Phase 2 and Phase 3, which were designed in consultation with the FDA to explore the CIN benefit of novel agent plinabulin. We are very pleased to announce that all four studies were positive and met their primary and key secondary endpoints,” said Ramon Mohanlal M.D., Ph.D., Chief Medical Officer and Executive Vice President of Research and Development at BeyondSpring. “All these four studies support the combination regimen of plinabulin and G-CSF for an intended broad label to prevent CIN in all solid tumors and all chemotherapy, which is included in our NDA filing.”
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.
About Plinabulin CIN NDA Program
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.
Headquartered in New York City, BeyondSpring is a global biopharmaceutical company focused on developing innovative cancer therapies to improve clinical outcomes for patients who have high unmet medical needs. BeyondSpring’s first-in-class lead asset plinabulin, is being developed as a “pipeline in a drug.” It is filed for approval in the US and China for the prevention of CIN and has a fully enrolled pivotal study to test an anti-cancer benefit with an overall survival primary endpoint in NSCLC. Additionally, it is being broadly studied in combination with various immuno-oncology regimens that could boost the effects of PD-1 / PD-L1 antibodies, and re-sensitize PD-1/PD-L1 antibody resistant patients. In addition to plinabulin, BeyondSpring’s extensive pipeline includes three pre-clinical immuno-oncology assets and a subsidiary, SEED Therapeutics, which is leveraging a proprietary targeted protein degradation drug discovery platform.
Cautionary Note Regarding Forward-Looking Statements
This press release includes forward-looking statements that are not historical facts. Words such as “will,” “expect,” “anticipate,” “plan,” “believe,” “design,” “may,” “future,” “estimate,” “predict,” “objective,” “goal,” or variations thereof and variations of such words and similar expressions are intended to identify such forward-looking statements. Forward-looking statements are based on BeyondSpring’s current knowledge and its present beliefs and expectations regarding possible future events and are subject to risks, uncertainties and assumptions. Actual results and the timing of events could differ materially from those anticipated in these forward-looking statements as a result of several factors including, but not limited to, difficulties raising the anticipated amount needed to finance the Company’s future operations on terms acceptable to the Company if at all, unexpected results of clinical trials, delays or denial in the regulatory approval process, results that do not meet our expectations regarding the potential safety, the ultimate efficacy or clinical utility of our product candidates, increased competition in the market, and other risks described in BeyondSpring’s most recent Form 20-F on file with the U.S. Securities and Exchange Commission. All forward-looking statements made herein speak only as of the date of this release and BeyondSpring undertakes no obligation to update publicly such forward-looking statements to reflect subsequent events or circumstances, except as otherwise required by law.
Ashley R. Robinson
LifeSci Advisors, LLC
Darren Opland, Ph.D.