The FDA has decided not to approve plinabulin with granulocyte colony-stimulating factor for the prevention of chemotherapy-induce neutropenia until further research is conducted.
A complete response letter (CRL) has been issued by the FDA to the developer of plinabulin regarding a new drug application for the drug in combination with granulocyte colony-stimulating factor (G-CSF) for the prevention of chemotherapy-induce neutropenia (CIN), announced BeyondSpring Pharmaceuticals, in a press release.1
The FDA originally granted priority review to the NDA, but the CRL stated that the single registrational trial used to support the application was not sufficient to prove the benefit of the combination. The FDA requires a second trial with a controlled design to provide evidence for the use of plinabulin plus G-CSF for prevent CIN.
“BeyondSpring strongly believes that plinabulin in combination with G-CSF has significant potential to raise the standard of care in CIN, a devastating side effect of chemotherapy,” said Lan Huang, PhD, BeyondSpring’s co-founder, chief executive officer, and chairwoman. “The company plans to request a meeting with the FDA and remains committed to its goal of bringing plinabulin to cancer patients in need globally.”
The NDA for plinabulin plus G-CSF was supported by findings from the pivotal phase 3 PROTECTIVE-2 study (NCT0329457), which is a randomized, double-blind study of about 221 patients. The primary end point of the study is the percentage of patients with duration of severe neutropenia (DSN), and the secondary end points include mean DSN assessment, percentage of patients with grade 3 or grade 4 neutropenia, and average change in bone pain.
Patients enrolled in PROTECTIVE-2 were randomized to either an arm of chemotherapy and the G-SCF agent pegfilgrastim (Neulasta) with placebo, or chemotherapy plus a combination of plinabulin and pegfilgrastim. Plinabulin was administered at a dose level of 40 mg in the study by 30-minute infusion.
The most recent data available for the combination shows that it greatly improved the rate of prevention of grade 4 neutropenia (13.6%) compared with 31.5% in the control arm (P = .0015). All secondary end points of the study have already been met. In terms of safety, the combination of plinabulin with G-SCF was well-tolerated in patients after achieving an over 20% reduction of grade 4 treatment-emergent adverse events. Quality of life was also improved for patients treated with the experimental combination.2
Those eligible to enroll were females aged 18 years or older who were candidates for at least 4 cycles of chemotherapy. All patients were required have a life expectancy of at least 3 months. Patients who had a history of myelogenous leukemia, myelodysplastic syndrome, or sickle cell disease were not eligible to enroll in the study. Patients receiving any anticancer therapies were ineligible.
Currently, there is no FDA approved therapy for the prevention of CIN, and plinabulin is the first drug candidate submitted to the FDA for its potential to prevent CIN in patients.1
1. BeyondSpring Pharmaceuticals receives complete response letter from the fda for plinabulin new drug application for prevention of chemotherapy-induced neutropenia (CIN). News release. BeyondSpring Pharmaceuticals. December 1, 2021. Accessed December 1, 2021. https://bit.ly/3EhnNTW
2. BeyondSpring announces submission of New Drug Application to the U.S. FDA and China NMPA for Plinabulin and G-CSF Combination for the prevention of chemotherapy-induced neutropenia. News Release. March 31, 2021. Accessed December 1, 2021. https://bit.ly/3cHfi9B