BeyondSpring Announces Three Presentations Highlighting Positive Clinical Outcome Data from the Phase 3 Program of Plinabulin in Combination with Pegfilgrastim for the Prevention of Chemotherapy-Induced Neutropenia at the American Society of Clinical Oncology (ASCO) Annual Meeting

Rhea-AI Summary

BeyondSpring announced positive results from the PROTECTIVE-2 Phase 3 clinical trial of plinabulin combined with pegfilgrastim for preventing chemotherapy-induced neutropenia (CIN). The combination therapy demonstrated a 50% reduction in both the incidence and duration of febrile neutropenia (FN) compared to pegfilgrastim alone, with 3.6% incidence versus 6.3%. Additionally, it decreased hospitalization duration significantly to 3.75 days from 7.14 days. The data supports the combination's effectiveness in improving quality of life and has led to NDA submissions in the U.S. and China.

Positive

• Combination therapy reduced FN incidence by 50% (3.6% vs. 6.3%)
• Duration of FN decreased to 1.25 days from 2.28 days
• Hospitalization duration halved to 3.75 days compared to pegfilgrastim
• NDA submissions for plinabulin and pegfilgrastim combination accepted with Priority Review

Negative

• None.

- Data demonstrate that combination of plinabulin and pegfilgrastim offers superior benefit for reducing the incidence and severity of febrile neutropenia (FN) and hospitalization, with better quality-of-life (QoL), compared to pegfilgrastim alone

NEW YORK, June 07, 2021 (GLOBE NEWSWIRE) -- BeyondSpring Inc. (the “Company” or “BeyondSpring”) (NASDAQ: BYSI), a global biopharmaceutical company focused on the development of innovative cancer therapies, today announced the presentation of three abstracts reporting on data from the PROTECTIVE-2 Phase 3 clinical program of plinabulin in combination with pegfilgrastim for prevention of Chemotherapy-induced neutropenia (CIN) at the American Society of Clinical Oncology (ASCO) Annual Meeting being held on June 4 - 8, 2021.

“Chemotherapy-induced neutropenia continues to represent an unmet medical need despite the use of G-CSF, thus novel approaches are needed. Chemotherapy will continue to be used either alone or in combination with immunotherapy. The addition of plinabulin to G-CSF, including pegfilgrastim, recently received the Breakthrough Designation and NDA Priority Review from both the U.S. FDA and China NMPA, solidifying the validity of the concept combining two complementary CIN agents. The combination achieved superior results over standard on care pegfilgrastim (G-CSF) alone, especially when considering important measures of clinical benefit such as febrile neutropenia rates and hospitalization in addition to patient quality of life," said Dr. Douglas Blayney, Professor of Medicine at Stanford University Medical School and global PI for CIN studies.

The poster, titled “Clinical Trial Testing Superiority of Combination Plinabulin (Plin) and Pegfilgrastim (Peg) vs Peg Alone in Patients (pts) with Breast Cancer treated with High Febrile Neutropenia Risk chemotherapy (chemo): Final results of the Phase 3 Chemo-Induced Neutropenia (CIN) Prevention Trial (PROTECTIVE-2)” was presented at 9:00 a.m. ET on June 4, 2021, at Lung Cancer Poster Session (Abstract #533). The superiority in ANC (absolute neutrophil number) based endpoints are correlated with improved clinically meaningful outcome measures of CIN, including FN and hospitalization, in ITT population.

• Reduction in incidence and severity of FN: The FN incidence (3.6%) in the combination arm is approximately 50% of that of the pegfilgrastim arm (6.3%), and has 50% shorter duration of FN (1.25 day vs. 2.28 day);
• Reduction in duration of hospitalization: Duration of hospitalization is approximately 50% less in the combination arm (3.75 day) compared to that in pegfilgrastim arm (7.14 day);
• Reduction in change in chemo dose and/or regimen in later cycles: The clinical consequence of changing chemo dose and/or chemo regimen in later cycles is approximately 50% lower in the combination vs. pegfilgrastim alone (2.7% vs. 6.3%).
  

The poster, titled “Chemotherapy Induced Profound Neutropenia (PN) in Patients (pt) with Breast Cancer (BC) after chemotherapy and Plinabulin (Plin) plus Pegfilgrastim (Peg) Combination versus (vs) Peg Alone. Final Phase 3 Results from PROTECTIVE-2 (BPI-2358-106),” was presented at 9:00 a.m. ET on June 4, 2021, at Lung Cancer Poster Session (Abstract #546) additionally highlights the superiority of the plinabulin combination, in reducing the incidence of the most severe form of neutropenia, profound neutropenia (ANC < 0.1 x 10⁹ cells/L), by more than 50% in incidence (21.6% vs. 46.4%, p=0.001) as well as the duration of profound neutropenia (0.34 days vs 0.63 days, p=0.0004), which is correlated with reduction of clinical consequences of FN and hospitalization in these profound neutropenia patients.

• Reduction of incidence of FN from 13.7% in pegfilgrastim arm to 4.2% in the combination arm for patients with profound neutropenia;
• Reduction of hospitalization rate from 11.8% in pegfilgrastim arm to 8.3% in the combination arm for patients with profound neutropenia.

The third poster, titled “Impact of Adding Plinabulin to Pegfilgrastim for the Prevention of TAC Chemotherapy (Chemo) Induced Neutropenia (CIN), on Patient Quality of Life (QoL),” was presented on June 4, 2021, at Lung Cancer Poster Session (Abstract #e24031). This is the first study to quantify physical wellbeing (pain and energy levels) of patients receiving plinabulin in combination with pegfilgrastim compared to pegfilgrastim alone.

• Better QoL with faster recovery from chemotherapy treatment: The combination performed significantly better on Days 8 and 15 of Cycle 2 of chemotherapy (p<0.0589 and p<0.0039 respectively) as well as Days 8 and 15 in Cycle 3 (p<0.0360 and p<0.0343 respectively), suggesting these patients recovered their pre-chemo wellbeing more rapidly than those treated with pegfilgrastim alone.
  

“We are very pleased to announce new positive clinical outcome data from the PROTECTIVE-2 Phase 3 program. The three ASCO abstracts provide collective evidence of plinabulin and pegfilgrastim combination’s superior effectiveness for the prevention of CIN compared to pegfilgrastim alone, not only in ANC based endpoints, but also in clinical outcome, including FN, hospitalization, and QoL. These benefits contribute to favorable benefit and risk ratio of this regimen, which address the current unmet medical needs in CIN.” Said Ramon Mohanlal M.D., Ph.D., Chief Medical Officer and Executive Vice President of Research and Development at BeyondSpring.

The Company has submitted New Drug Applications (NDA) for plinabulin in combination with pegfilgrastim as a treatment for the prevention of CIN for review 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.

About CIN
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.

About Plinabulin
Plinabulin, BeyondSpring’s lead asset, is a selective immunomodulating microtubule-binding agent (SIMBA). It is a novel, intravenous infused, patent-protected, NDA ready asset for CIN prevention indication and a Phase 3 anti-cancer candidate 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 US and China FDA for CIN prevention indication. As a “pipeline in a drug,” plinabulin is being broadly studied in combination with various immuno-oncology agents that could boost the effects of the PD-1/PD-L1 antibodies and re-sensitize PD-1/PD-L1 antibody resistant patients.

About BeyondSpring
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 chemotherapy-induced neutropenia (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.

Investor Contact:
Ashley R. Robinson
LifeSci Advisors, LLC
+1 617-430-7577
arr@lifesciadvisors.com

Media Contact:
Darren Opland, Ph.D.
LifeSci Communications
+1 646-627-8387
darren@lifescicomms.com

FAQ

What are the results of the PROTECTIVE-2 trial for BYSI?

The PROTECTIVE-2 trial showed that plinabulin in combination with pegfilgrastim significantly reduced the incidence and severity of febrile neutropenia, with a FN incidence of 3.6% compared to 6.3% with pegfilgrastim alone.

What is the significance of the NDA submission for BYSI?

The NDA submission for plinabulin and pegfilgrastim combination indicates a potential new treatment option for chemotherapy-induced neutropenia, enhancing the company's market prospects.

What is the expected action date for the BYSI NDA?

The U.S. FDA has set a Prescription Drug User Fee Act (PDUFA) action date of November 30, 2021, for the review of the NDA.

How does plinabulin improve patient quality of life according to the trial?

Patients treated with the combination of plinabulin and pegfilgrastim reported quicker recovery and improved physical wellbeing compared to those receiving pegfilgrastim alone.

What is the main benefit of the combination therapy reported in the press release?

The combination therapy addresses the unmet medical need for reducing complications associated with chemotherapy-induced neutropenia, including febrile neutropenia and hospitalization.