FDA Grants Priority Review to Plinabulin With G-CSF for Prevention of Chemotherapy-Induced Neutropenia

The FDA has accepted and granted priority review to the new drug application (NDA) for plinabulin in combination with granulocyte colony-stimulating factor (G-CSF) for the prevention of chemotherapy-induced neutropenia (CIN) in patients with cancer, according to a press release from BeyondSpring, Inc.¹

Plinabulin, a selective immune-modulating microtubule-binding agent is the first agent being considered for FDA approval to prevent the onset and progression of CIN.

The NDA for the plinabulin combination 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.

"We are pleased that the FDA has accepted with priority review our NDA filing for plinabulin, which is one of the key milestones for this product in 2021. We look forward to continue to work closely with the FDA through the review process," said Dr. Lan Huang, PhD, co-founder, chief executive officer, and chairwoman of BeyondSpring. "Chemotherapy is a very important therapy regimen for cancer patients, even more so with its approval in combination with checkpoint inhibitors. With COVID-19, the [National Comprehensive Cancer Network] panel had updated the guidelines to potentially double the patient population included in CIN prevention. If approved, plinabulin and G-CSF combination would be an important new and improved option to prevent CIN for approximately 467,500 cancer patients in the [United States] annually."

In the study, patients were randomly assigned to receive either chemotherapy and the G-SCF agent pegfilgrastim (Neulasta) and 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.

According to a previous report from BeyondSpring, the PROTECTIVE-2 study met its primary end point. The rate of prevention of grade 4 neutropenia was greatly improved with the experimental combination from 13.6% to 31.5% (P = .0015).^1,2 All secondary end points of the study have also been met. Plinabulin with G-SCF was also found to be well-tolerated in patients after achieving an over 20% reduction of grade 4 treatment-emergent adverse events. The events improved upon with the experimental combination compared with pegfilgrastim alone were bone pain and quality-of-life.¹

Patients were eligible to be treated in the PROTECTIVE-2 trial if they were females aged 18 years or older and were candidates for at least 4 cycles of chemotherapy. All patients were required to also have a life expectancy of at least 3 months. Those who had a history of myelogenous leukemia, myelodysplastic syndrome, or sickle cell disease were not eligible to enroll in the study. Patients also could not be receiving any anticancer therapies.

_References:

_{1. BeyondSpring announces U.S. FDA acceptance and priority review of new drug application for plinabulin and G-CSF combination for the prevention of chemotherapy-induced neutropenia (CIN). News release. BeyondSpring, Inc. June 1, 2021. Accessed June 1, 2021.}

_{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 June 1, 2021. https://bit.ly/3cHfi9B}