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BeyondSpring Presents Lead Asset’s Mechanism Data for Prevention of Chemotherapy-Induced Neutropenia
The preclinical study evaluated Plinabulin’s role in regulating neutrophil biology and docetaxel CIN. Mice were intravenously treated with a single injection of docetaxel at 25 mg/kg, with and without Plinabulin at 10 mg/kg or 20 mg/kg, into the abdominal cavity, one hour later. The Plinabulin 10 mg/kg in mice corresponds to dose levels in humans that are used in our current clinical trials. Complete blood counts (CBC) were performed at three, four and five days post-injection, with bone marrow analysis after five days.
Plinabulin significantly reduced docetaxel-induced neutropenia at Day Five (p<0.05) in this mouse study. Bone marrow neutrophil counts were decreased by docetaxel monotherapy, but reduction in bone marrow neutrophil counts was prevented when Plinabulin was administered with docetaxel (for Plinabulin at 10 mg/kg, p<0.001; for Plinabulin at 20 mg/kg, p<0.01). The docetaxel-induced accumulation of uncommitted hematopoietic stem cells (LSK cells) was significantly prevented by Plinabulin, and Plinabulin’s effect appeared to be neutrophil-specific; Plinabulin had no effect on monocytes. Collectively, these data suggest that Plinabulin reduces CIN by protecting the normal transition of LSK to myeloid precursors in mice (which is arrested by docetaxel alone) and represent a novel mechanism for the prevention of CIN.
CIN is a common side effect of many cancer chemotherapies that results from the absence of neutrophils, which are critical in the defense against infections. Cancer patients who develop CIN are more susceptible to severe and life-threatening infections, may have their chemotherapy treatment reduced or interrupted and may require hospitalization.
The current standard of care in the prevention of CIN is G-CSF (granulocyte colony stimulating factor), which has important limitations: G-CSF causes medullary bone pain, as it stimulates the expansion and proliferation of neutrophil precursors in the central part (or medullary compartment) of bone marrow. This medullary or expansive bone pain is peculiar to conditions in which the bone marrow is extremely active. Furthermore, G-CSF must be administered 24 hours or more after the chemotherapy infusion (per the approved label). Thus, there is an unmet medical need for patients who suffer from CIN.
“The mechanistic data presented today validate the clinical data observed to date demonstrating that Plinabulin may produce less bone pain versus Neulasta in patients with CIN,” said Dr.
“In prospective clinical studies, Plinabulin has not only produced statistically significant reductions in severe neutropenia induced by docetaxel, but it can also be administered 30 minutes to one hour following chemotherapy and has been associated with less bone pain – two limitations associated with G-CSF,” added Dr.
Plinabulin is BeyondSpring’s lead clinical asset currently in global registrational studies for the prevention of CIN and treatment of NSCLC. Under BeyondSpring’s dual-market strategy, Plinabulin’s global development program is designed to support New Drug Application (NDA) submissions in
About Chemotherapy-Induced Neutropenia (CIN)
The current standard of care for prevention of CIN is G-CSF, which accelerates maturation and proliferation of neutrophil precursors, and, when administered the day after chemotherapy, reduces DSN of docetaxel to less than one day. G-CSF has the limitation of second-day dosing after chemotherapy treatment and bone pain in 10 to 29 percent of patients, with some patients citing bone pain as “excruciating.” For the intermediate-risk chemotherapy market, which represents 60 percent of cases, National Comprehensive Cancer Network (NCCN) guidelines recommend G-CSF treatment only in limited, patient-specific circumstances.
Global sales of G-CSF totaled more than
Cautionary Note Regarding Forward-Looking Statements
Neulasta is a registered trademark of