Phase 2 Data Show Plinabulin Significantly Reduces Thrombocytopenia in Docetaxel-Treated Patients Compared to Standard of Care
Data Presented at 2018 IASLC World Conference on Lung Cancer
NEW YORK, Sept. 25, 2018 (GLOBE NEWSWIRE) -- BeyondSpring Inc. (NASDAQ:BYSI), a global, clinical-stage biopharmaceutical company focused on the development of innovative cancer therapies, presented clinical trial data on its novel lead asset, Plinabulin, during a poster presentation at the International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer in Toronto, Canada.
New data from the Company’s Phase 2 portion of the Phase 2/3 trial in Study 105 of Plinabulin was presented by Dr. Douglas Blayney, global Principal Investigator for BeyondSpring’s chemotherapy-induced neutropenia (CIN) development program and Professor of Medicine at Stanford University Medical Center. The poster presentation is titled, “Plinabulin, a Novel Immuno-Oncology Agent Mitigates Docetaxel Chemotherapy-Induced Neutropenia and Thrombocytopenia in NSCLC Patients.”
Thrombocytopenia, a frequent side effect of chemotherapy, is a lowering of platelet counts that, when severe, leads to bleeding and anemia and can require transfusion with platelets, potentially resulting in a long ICU stay, as well as a high mortality rate.
In a head-to-head Phase 2 trial comparing Plinabulin with Neulasta® (pegfilgrastim), a long-acting G-CSF, Plinabulin at 20 mg/m2 (n=14) was shown to be effective in significantly reducing docetaxel-induced thrombocytopenia (p<0.001 to p<0.05 over different timepoints in Cycle 1), while Neulasta (n=14) did not show this benefit.
- Nearly half (45 percent) of patients who received Neulasta experienced thrombocytopenia (any grade) in Cycle 1, compared to 0 percent of patients who received 20 mg/m2 of Plinabulin.
- Plinabulin’s platelet-protective effect also carried through all four cycles in this study in a statistically significant manner. Clinically significant thrombocytopenia – which is defined as a decrease in platelet counts of more than 30 percent – had occurred much less in patients who received docetaxel + Plinabulin, compared to patients who received docetaxel + Neulasta over all four cycles (p=0.019).
“The platelet protection data from this study further strengthens Plinabulin’s superior product profile compared to Neulasta through demonstrating anti-cancer activity, less bone pain and the benefit of same-day dosing, compared to next-day dosing with Neulasta,” said Dr. Blayney. “This further reinforces our confidence in the novel mechanism of action for Plinabulin, and we look forward to interim data from the Phase 3 portion of the study by the end of 2018 or early 2019.”
About Study 105
The study evaluated patients with advanced or metastatic NSCLC after failing platinum-based therapy and was designed as a multicenter, open label, randomized study. In a head-to-head comparison of Plinabulin with Neulasta, a long-acting G-CSF, in a total of 55 patients, Plinabulin was shown to be comparable to Neulasta for the prevention of CIN as assessed by the occurrence of severe (Grade 4) neutropenia and the duration of severe neutropenia (DSN) in the first cycle.
Plinabulin was given as a single dose per cycle 30 minutes after docetaxel chemotherapy, while Neulasta was given 24 hours after docetaxel chemotherapy, consistent with its approved product label. The Phase 2 portion met its primary endpoint, which was to determine the recommended Phase 3 Plinabulin dose, and the Phase 3 trial is now underway.
Plinabulin, a marine-derived small-molecule, is BeyondSpring’s lead asset and currently in late-stage clinical development for the prevention of CIN and as an anticancer therapy in NSCLC. Studies of Plinabulin's mechanism of action indicate that Plinabulin activates GEF-H1, a guanine nucleotide exchange factor. GEF-H1 activates downstream transduction pathways leading to the activation of the protein c-Jun. Activated c-Jun enters the nucleus of dendritic cells to up-regulate immune-related genes, which contributes to the up-regulation of a series of genes leading to dendritic cell maturation, T-cell activation and other effects that prevent neutropenia by reducing the neutrophil breakdown.
About Chemotherapy-Induced Neutropenia (CIN)
CIN is a common side effect in cancer patients undergoing treatment that involves the destruction of a type of white blood cell, the neutrophil, which is a patient’s first line of defense against infections. Patients with grade 4 (severe) neutropenia have an abnormally low concentration of neutrophils, making these patients more susceptible to bacterial and fungal infections / sepsis, which can require hospitalization. When patients experience severe neutropenia, the oncologist is faced with a choice of compromising the chemotherapy, delaying the cycle or stopping therapy until the neutropenia subsides, which may result in significantly reduced long-term survival for the patient.
The current standard of care for CIN prevention is G-CSF, which accelerates the maturation and proliferation of neutrophil precursors. G-CSFs have serious limitations due to the excruciating bone pain that they may cause in some patients. In addition, G-CSFs may require patients to revisit the oncology clinic the day after chemotherapy, causing a significant inconvenience for some patients. Despite these setbacks, global sales for G-CSFs totaled more than $8 billion in 2017, with the current market leader, Neulasta, contributing approximately $6 billion. In the U.S. alone, Neulasta sales totaled more than $4 billion in 2016.
According to the CDC, approximately 650,000 patients receive outpatient chemotherapy in the U.S., and CIN remains a critical clinical problem despite 25+ years of G-CSF availability. Existing CIN therapies fail to address adverse events and efficacy issues that may cause doctors to lower target doses of chemotherapy (patients receive less than 85 percent of their target dose), end therapy early and / or delay chemotherapy cycles, each of which has a negative effect on long-term outcomes of cancer care.
BeyondSpring is a global, clinical-stage biopharmaceutical company developing innovative immuno-oncology cancer therapies with a robust pipeline from internal development and from collaboration with University of Washington in de novo drug discovery using a ubiquitination platform. BeyondSpring’s lead asset, Plinabulin, is in a Phase 3 global clinical trial as a direct anticancer agent in the treatment of non-small cell lung cancer (NSCLC) and two Phase 2/3 clinical programs in the prevention of chemotherapy-induced neutropenia (CIN). BeyondSpring has a seasoned management team with many years of experience bringing drugs to the global market.
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 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.
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