NEW YORK, Dec. 14, 2017 (GLOBE NEWSWIRE) -- BeyondSpring Inc. (NASDAQ:BYSI), a global clinical stage biopharmaceutical company focused on the development of innovative immuno-oncology cancer therapies, today announced that the Company has met the primary objective in the Phase 2 portion of its global Phase 2/3 clinical trial (Study 105) for the prevention of CIN with docetaxel, comparing BeyondSpring’s lead asset, Plinabulin to pegfilgrastim (Neulasta), a long-lasting G-CSF, and will soon begin the Phase 3 portion of Study 105. Initial data from the Phase 2 portion of Study 105 will be presented at the 2018 ASCO-SITC Clinical Immuno-Oncology Symposium in San Francisco on Jan. 25-27, 2018.
In addition, the Company announced that a p value of < 0.0001 from its ongoing Phase 3 NSCLC clinical trial (Study 103) was achieved from 138 patients on a secondary endpoint of grade 4 neutropenia, which demonstrates Plinabulin’s ability to reduce docetaxel CIN. This data review does not subject the study to a statistical penalty. Interim anti-cancer efficacy data from Study 103 is expected in mid-2018.
In Study 105, Plinabulin meets the primary objective of the recommended Phase 3 dose selection.
- Patients with NSCLC were randomized to arm 1 (docetaxel + pegfilgrastim (G-CSF)), arm 2 (docetaxel + Plinabulin 5 mg/m2), arm 3 (docetaxel +Plinabulin 10 mg/m2;), or arm 4 (docetaxel + Plinabulin 20 mg/m2).
- Pegfilgrastim was given as a single dose, 24 hours after docetaxel use, while Plinabulin was given on Day 1, 0.5-1 hour after docetaxel use. The docetaxel dose was 75 mg/m2 in all patients.
- The primary endpoint, DSN in the first treatment cycle (duration of severe / grade 4 neutropenia), is defined as the number of days that a patient experiences grade 4 neutropenia, or a neutrophil count < 0.5 x 109 cells/L from a blood draw.
In Study 103, data from 138 patients demonstrate that Plinabulin reduced the percentage of patients with grade 4 neutropenia resulting from docetaxel therapy from 27.4 percent to 3.1 percent (p<0.0001).
- Study 103 includes NSCLC patients randomized to Plinabulin+docetaxel (n=277) or docetaxel (n=277). The primary endpoint is overall survival, and secondary endpoints include grade 4 neutropenia on Day 8 of cycle 1 (C1D8).
- Plinabulin (30 mg/m2) was dosed at Day 1 and 8 of each cycle. The neutrophil count from a blood draw was measured on C1D8 before the D8 dose of Plinabulin, thus showing effects after one dose of Plinabulin. The docetaxel dose was 75 mg/m2 in all patients.
- Grade 4 neutropenia on C1D8 is defined as a neutrophil count < 0.5 x 109 cells/L from a blood draw. The grade 4 neutropenia rate is defined as the percentage of patients experiencing a neutrophil count below 0.5 x 109 cells/L on C1D8.
To date, Plinabulin has been administered to over 270 patients globally and has generally been well-tolerated. The most common adverse effects seen in these patients were nausea, vomiting and transient hypertension.
“CIN is a clinical need that is not adequately addressed by G-CSF, which has seen little innovation for the last three decades,” said Dr. Douglas Blayney, global Primary Investigator for Study 105 and founding member of the NCCN board that establishes the guidelines for neutropenia treatment. “Plinabulin represents a novel alternative to G-CSF, with a superior target product profile over Neulasta, the current G-CSF market leader. Study 103 measures the C1D8 neutrophil number, which represents the lowest neutrophil count in a docetaxel cycle. This neutrophil count on day 8 predicts the duration in days that a patient has grade 4 (severe) neutropenia (DSN). Thus, the lower the neutrophil count is on day 8 or the higher the grade 4 neutropenia rate is, the longer the DSN, the primary endpoint of Study 105. Thus, the collective data generated thus far from Studies 103 and 105 confirm prospectively that Plinabulin is highly effective in the prevention of docetaxel CIN. It is gratifying to see this positive clinical data supported by strong mechanistic data on Plinabulin by Dr. Klaus Ley’s lab, a veteran in neutrophil study for 30 years.”
As a common side effect of chemotherapy in cancer patients, neutropenia is the lack of, or severe reduction in, the number of a type of white blood cell (neutrophil) that is a key component of the innate immune system. Neutrophils are a patient’s first line of defense against infections, and patients with severe (grade 4) neutropenia (an abnormally low concentration of neutrophils in the blood) are more susceptible to severe bacterial, viral and fungal infections and sepsis, which require hospitalization and have a high mortality risk of 9 to 18 percent in the first cycle.
“The highly differentiated target product profile of Plinabulin compared with Neulasta has attracted significant attention of national health authorities, such as the FDA and CFDA, as well as from prominent investigators,” added Dr. Lan Huang, co-founder and CEO of BeyondSpring. “As a result, BeyondSpring has been able to advance its global neutropenia program quickly. We fully enrolled the last 50 patients of Study 105 in less than two months.”
“The Phase 2 data from Study 105 had the important primary objective of determining the recommended dose for the Phase 3 portion of this trial,” concluded Dr. Ramon Mohanlal, Chief Medical Officer at BeyondSpring. “This was also the first occasion to allow for a head-to-head comparison of Plinabulin versus Neulasta, albeit with a relatively small sample size. After analysis of the Phase 2 portion, the data provides the justification to move into the Phase 3. We believe that Plinabulin represents breakthrough advancement for patients with CIN indication.”
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 ubiquitination platform. BeyondSpring’s lead asset, Plinabulin, is in a Phase 3 clinical trial as a direct anticancer agent in non-small cell lung cancer (Study 103) and two Phase 2/3 clinical programs in the prevention of chemotherapy-induced neutropenia (CIN) – Studies 105 and 106. BeyondSpring has a seasoned management team with many years of experience bringing drugs to market.
Studies on 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 upregulate 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. Plinabulin is given as a single IV infusion in each cycle, 30 minutes to 1 hour after completion of the chemotherapy, offering same day dosing, whereas G-CSF is given 24 hours after chemotherapy. In addition, the use of Plinabulin is not associated with bone pain, which is a frequent side effect with G-CSF.
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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, the anticipated amount needed to finance the company's future operations, unexpected results of clinical trials, delays or denial in regulatory approval process, our expectations regarding the potential safety, efficacy or clinical utility of our product candidates, or additional competition in the market. The 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.