NEW YORK, May 17, 2018 (GLOBE NEWSWIRE) -- BeyondSpring Inc. (NASDAQ:BYSI), a global clinical-stage biopharmaceutical company focused on the development of transformative cancer therapies, today announced that the Company will present results of the Phase 2 portion of Study 105, a prospective Phase 2/3 trial of its lead asset, Plinabulin, during a poster presentation at the American Society of Clinical Oncology (ASCO) Annual Meeting on June 4, 2018. Importantly, data from the study demonstrated that patients treated with Plinabulin dosed 30 minutes after docetaxel for the prevention of docetaxel chemotherapy-induced neutropenia (CIN) reported less bone pain, which was clinically meaningful, and had superior neutrophil counts and comparable neutropenia reduction compared to patients treated with Neulasta® (pegfilgrastim) 24 hours after docetaxel. These findings suggest that Plinabulin has the potential for an overall superior product profile in the prevention of CIN.
Study 105 is part of BeyondSpring’s comprehensive development program for Plinabulin for the prevention of CIN. The Phase 2/3 study was designed as a head-to-head comparison of different dose levels of Plinabulin to Neulasta in a total of 55 patients. 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. Data from the Phase 2 portion, to be included in the poster presentation, are summarized below.
Similar Neutropenia Reduction
- Patients treated with one dose of Plinabulin at 20 mg/m2 had the same occurrence of severe neutropenia (grade 4) as patients treated with one dose of Neulasta (6 mg) in the first 21-day cycle; grade 4 neutropenia occurred in 14 percent of patients treated with either Plinabulin or Neulasta.
- Patients treated with Plinabulin at 20 mg/m2 demonstrated the same duration of severe neutropenia (DSN) in the first cycle compared to those treated with Neulasta. The DSN was 0.5 days for patients treated with either Plinabulin or Neulasta. DSN was calculated with an FDA-accepted method for small-sample-size extrapolation.
Plinabulin-Treated Patients Reported Two-Thirds Lower Rate of Bone Pain
- Bone pain, which was assessed with a validated questionnaire, occurred in fewer patients treated with Plinabulin at 20 mg/m2 (11 percent) compared to patients treated with Neulasta (33 percent). Neulasta’s ability to treat CIN is based on its mechanistic properties as a granulocyte colony-stimulating factor (G-CSF) that stimulates the expansion and proliferation of neutrophil precursors in the central part (medullary compartment) of bone marrow, which may cause severe bone pain, leading to discontinuation of chemotherapy treatment. In contrast, preclinical studies have shown that Plinabulin’s mechanism of action differs from G-CSF, allowing it to protect the neutrophil precursors but not induce their proliferation, which may result in less bone pain compared to G-CSF.
Plinabulin Preserved Neutrophil Number in Normal Range
- Plinabulin maintained median absolute neutrophil counts (a measure of neutrophils per unit of blood that is calculated from measurements of the total number of white blood cells and bands, or immature neutrophils) within normal range, whereas patients given Neulasta experienced median absolute neutrophil counts higher than the normal range, which can potentially cause bone marrow exhaustion. This provides further evidence of a different mechanism of action with Plinabulin compared to Neulasta for CIN.
“The Phase 2 data are extremely encouraging and underscore Plinabulin’s potential to address unmet needs in the treatment of CIN. These prospective data suggest that Plinabulin, given as a single dose per cycle, would be at least as effective as Neulasta, with the important benefit of causing less bone pain and enabling same-day dosing, compared with the next-day dosing per the G-CSF label. The neutrophil levels observed in this trial are also noteworthy, suggesting a different mechanism of action for Plinabulin compared with G-CSF,” said Dr. Douglas Blayney, global Principal Investigator for BeyondSpring’s CIN development program and Professor of Medicine at Stanford University. “The fact that Plinabulin has demonstrated anticancer efficacy in a previous non-small cell lung cancer (NSCLC) Phase 2 study—which is anticipated to be confirmed in the ongoing NSCLC Phase 3 clinical trial—is another distinct advantage. Overall, these differences indicate that Plinabulin has the potential for a superior product profile in the prevention of CIN.”
“These are the first head-to-head comparison data between Plinabulin and Neulasta. We are highly encouraged by these Phase 2 trial results, and subject to confirmatory Phase 3 trial data, we plan to submit a New Drug Application (NDA) for CIN to the China Food and Drug Administration (CFDA) in late 2018 or early 2019, and a U.S. NDA in 2019,” added Dr. Ramon Mohanlal, Chief Medical Officer at BeyondSpring.
“The CIN program with Plinabulin further illustrates BeyondSpring’s potential and our commitment to bringing first-in-class drugs to the market to serve important areas with unmet medical needs,” concluded Dr. Lan Huang, BeyondSpring’s CEO.
ASCO Poster Presentation on June 4, 2018, 8-11 a.m. CDT in Chicago
The poster titled, “Plinabulin (Plin), a small molecule with anti-cancer activity and a novel mechanism of action (MoA) in docetaxel (Tax)-induced neutropenia: Phase 2 results from a head-to-head comparison with Pegfilgrastim (Peg),” will be presented on June 4, 2018, from 8 to 11 a.m. CDT in Hall A at McCormick Place. The poster will be part of a session titled, “Developmental Therapeutics—Clinical Pharmacology and Experimental Therapeutics.”
About Chemotherapy-Induced Neutropenia (CIN)
CIN is a common side effect in cancer patients that involves the destruction of a type of white blood cell (neutrophil), which are a patient’s first line of defense against infections. Patients with severe, or grade 4, neutropenia have an abnormally low concentration of neutrophils, making them more susceptible to severe bacterial and fungal infections and sepsis, which can require hospitalization. When severe neutropenia occurs, the chemotherapy dose has to be reduced or interrupted until the neutropenia subsides. Up to 18 percent of patients could die from first-cycle chemotherapy treatment, according to Cancer Network. The severity of neutropenia is measured by DSN, which measures the days a patient has a dangerously low neutrophil count. DSN of less than one day is considered clinically meaningful.
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 some 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 $8 billion in 2016, with the current G-CSF market leader, Neulasta, contributing approximately $6 billion. In the U.S., Neulasta sales totaled more than $4 billion in 2016. According to the CDC, about 650,000 patients receive outpatient chemotherapy in the U.S. Approximately 4 million new patients are diagnosed with cancer in China each year, according to the American Cancer Journal of Clinicians, and up to 65 percent of patients use chemotherapy, according to a nationwide study.
Plinabulin, a marine-derived small-molecule, is BeyondSpring’s lead asset and is 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.
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 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, 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, additional competition in the market, and other risk factors referred to in BeyondSpring’s current Form 20-F on file with the U.S. Securities and Exchange Commission. 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.
Neulasta is a registered trademark of Amgen, Inc.
Laura Perry / Joe Rayne