Data Presented Shows Addition of Plinabulin Enhances Neulasta’s Efficacy and Reverses Potential Immune-Suppressive Phenotype
NEW YORK , March 05, 2019 (GLOBE NEWSWIRE) -- BeyondSpring Inc. (NASDAQ: BYSI), a global biopharmaceutical company focused on the development of innovative cancer therapies, presented new clinical results from its Study 106 program in the prevention of chemotherapy induced neutropenia (CIN) for its lead asset Plinabulin at the 2019 ASCO-SITC Clinical Immuno-Oncology Symposium. The data showed that, through combining Plinabulin with Neulasta, patients not only experienced better outcomes for CIN treatment, but Neulasta’s potential immune-suppressive phenotype was also reduced.
Neulasta, a long acting G-CSF and the current standard of care for CIN, activates the bone marrow, resulting in a temporary overproduction of neutrophils, many of which are immature. Immature neutrophils can travel to the tumor tissue and cause the microenvironment to be immune-suppressive. Established markers for immune-suppression are high Neutrophil-to-Lymphocyte Ratio (NLR>5) and low Lymphocyte-to-Monocyte Ratio (LMR<3.2), which are associated with low survival outcomes. Previously, BeyondSpring presented data from its Study 105 (using docetaxel as an example of intermediate-risk chemotherapy), which showed that Neulasta, but not Plinabulin, caused levels of NLR>5 and LMR<3.2 in most patients (Blayney, ESMO 2018, SITC 2018).
BeyondSpring evaluated whether combining Plinabulin with Neulasta would reverse the immune-suppressive neutrophil profile induced by Neulasta. BeyondSpring’s Study 106 uses Taxotere, Doxorubicin and Cyclophosphamide (TAC) as an example of high febrile neutropenia (FN) risk chemotherapy. Patients were randomly assigned to treatment arms with Neulasta alone, Neulasta combined with Plinabulin or Plinabulin alone. The analysis in this abstract evaluated patients from the following arms in Study 106:
- Pegfilgrastim (6 mg) (n=22)
- Plinabulin (20 mg/m2) + Pegfilgrastim (6 mg) (n=16)
- Plinabulin (20 mg/m2) (n=15)
The combination of Plinabulin with Neulasta resulted in better protection against CIN. Importantly, the data also demonstrates that adding Plinabulin to Neulasta reverses the immune-suppressive profile of Neulasta by lowering the percentage of patients with a Neutrophil-to-Lymphocyte Ratio (NLR) of less than 5 (p<0.007) or with a Lymphocyte-to-Monocyte Ratio (LMR) of greater than 3.2 (p<0.07) versus Neulasta alone.
“As thousands of people suffer from chemotherapy-induced neutropenia around the world, combination therapies offer a superior treatment compared to the status quo today,” said Dr. Douglas Blayney, global Principal Investigator for BeyondSpring’s CIN development program and Professor of Medicine at Stanford University Medical Center. “The Plinabulin and full Neulasta combination not only is more effective than either alone, but also significantly reduces bone pain and improves patients’ quality of life. This new data that we presented at ASCO-SITC will benefit both patients and their physicians. We think our combination therapy is the future of cancer care.”
“The observation that adding Plinabulin to Neulasta leads to a reversal of the immune-suppressive profile may have an important impact on patient outcomes, as maintaining an optimal immune response against cancer is very important for patient survival. With the new treatment landscape of combinations in chemotherapy and immunotherapy, such as PD-1 antibodies, this Plinabulin and Neulasta combination would be a timely option for the prevention of CIN in this population,” added Dr. Ramon Mohanlal, EVP of R&D and Chief Medical Officer at BeyondSpring. “This sets the stage for BeyondSpring’s New Drug Application (NDA) filings in both the U.S. and China later this year.”
Plinabulin, a marine-derived small-molecule that sequesters tubulin heterodimers in a manner differentiated from other agents in this class, is BeyondSpring’s lead asset. Following positive Phase 2 results, Plinabulin is currently in late-stage clinical development to increase overall survival in cancer patients, as well as to alleviate chemotherapy-induced neutropenia in non-small cell lung cancer. Plinabulin reduced chemotherapy-induced neutropenia in association with reduced thrombocytopenia and increased circulating CD34+ progenitor cell mobilization in patients. Studies of Plinabulin's mechanism of action in animals indicate that these broad effects on the hematopoietic system may relate to positive effects on hematopoietic stem / progenitor cells in the bone marrow, with increased tissue cytokine / IL-6 secretion. The anticancer benefits of targeting tubulin / microtubules with Plinabulin have been associated with positive effects on antigen presenting cells and T-cell activation, as well as to the direct killing of cancer cells.
About Chemotherapy-Induced Neutropenia
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. The current standard of care for CIN prevention is G-CSF monotherapy. However, G-CSF monotherapy has limitations as described in its product information summary.
As many as 90 percent of patients on high-risk chemotherapy and G-CSF monotherapy may still experience grade 3 or 4 neutropenia (Lee et al., Annals of Surgical treatment and research 94(5): 223-228 (2018)). Patients with grade 4 (severe) neutropenia have an abnormally low concentration of neutrophils, making these patients more susceptible to bacterial and fungal infections and sepsis, which can require hospitalization and be fatal. Grade 4 CIN can have an adverse effect on chemotherapy administration and is usually considered a significant predictor of low relative dose intensity (RDI), dose delays and dose reductions (Lalami Y, Critical Reviews in Oncology / Hematology, 120: 163 – 179 (2017)). A reduction in dose of as little as 15 percent can reduce long-term survival by as much as 50 percent (Bonadonna, Med Oncol 29:1495–1501 (2012)).
As many as 70 percent of patients using G-CSF monotherapy experience bone pain while on G-CSF monotherapy (Moore et al., Annals of Pharmacotherapy 51(9): 797-803 (2017)). Additionally, 25 percent of patients report that the pain is severe. NCCN guidelines require that patients with grade 3/4 neutropenia decrease chemotherapy dose intensity, delay chemotherapy cycle timing or discontinue chemotherapy, each of which can have a negative effect on the long-term outcomes of cancer care (Lalami et al., Critical Reviews in Oncology / Hematology 120: 163-179 (2017)).
BeyondSpring is a global, clinical-stage biopharmaceutical company focused on the development of innovative immuno-oncology cancer therapies. 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 and two Phase 2/3 clinical programs in the prevention of chemotherapy-induced neutropenia. BeyondSpring has internal R&D capabilities with a robust pipeline including, in addition to Plinabulin, three immuno-oncology assets and a drug discovery platform using ubiquitination degradation pathway. The Company 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.
Neulasta® is a registered trademark of Amgen, Inc.
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