A New Drug Application has been submitted to the FDA for the combination of plinabulin and granylocyte colony-stimulating factor for the prevention of chemotherapy-induced neutropenia.
A New Drug Application (NDA) has been submitted to the FDA for the combination of plinabulin and granylocyte colony-stimulating factor (G-CSF) for the prevention of chemotherapy-induced neutropenia (CIN), according to a press release by BeyondSpring, Inc.
Every year, 110,000 patients are hospitalized for CIN after receiving chemotherapy in the United States alone. The side effect of chemotherapy increases the risk of infection with fever and can be severe. The COVID-19 pandemic has increased the risk for many patients, prompting the National Comprehensive Cancer Network (NCCN) to expand the use of prophylactic G-CSFs from high-risk patients to intermediate-risk patients as well.
The NDA was filed based on the results of the phase 3 PROTECTIVE-2 trial (NCT03294577). The randomized, double-blind study has an actual enrollment of 221 patients with an estimated completion date of September 2025. The study has a primary outcome of percentage of patients with duration of severe neutropenia (DSN). Secondary outcomes include mean DSN assessment, percentage of patients with grade 3 or grade 4 neutropenia, and average change in bone pain.
Patients were randomized into 1 of 2 arms. In arm 1, patients received chemotherapy and pegfilgrastim (Neulasta), a G-CSF that is the current standard of care for patients at high-risk of CIN. Patients in this arm also received a placebo. In arm 2, patients received chemotherapy plus a combination of plinabulin and pegfilgrastim.
In order to participate patients must be women 18 years old or older who are candidates for at least 4 cycles of chemotherapy. Additionally, they must also have a life expectancy of 3 months or more. Patients with a history of myelogenous leukemia, myelodysplastic syndrome, or sickle cell disease are not eligible. Patients also cannot be receiving any anticancer therapies.
The study met its primary endpoint rate of prevention of grade 4 neutropenia was greatly improved in the experimental arm (improved from 13.6% to 31.5%, p=0.0015). The DSN for the combination regimen for cycle 1 from day 1 through 8 showed and ANC of <0.5x109 cells/L. This is superior to pegfilgrastim alone with a P = .0065.
“This NDA submission is the culmination of years of research to prove that plinabulin can improve the long-established standard of care and address an unmet medical need to further alleviate the risk burden of CIN for patients receiving chemotherapy,” said Lan Huang, PhD co-founder, CEO, and chairman of BeyondSpring. “With CIN responsible for potentially delaying treatment and causing life-threatening infections, we hope that receiving the improved care represented by the plinabulin and G-CSF combination will allow patients to better tolerate chemotherapy and potentially see increased treatment success rates. We are grateful for the patients’ participation in plinabulin’s clinical trials and the participation and contributions of our investigators and our many other clinical partners.”
If approved, the combination could be used to treat approximately 440,000 cancer patients in the United States annually. An application for approval of the combination was also filed with the China National Medical Products Administration. In China, an estimated 2.8 million new patients are treated with chemotherapy each year, with the G-CSF drug market growing by 30% a year.