Plinabulin Plus G-CSF Earn Priority Review From FDA for CIN

A new drug application (NDA) for plinabulin in combination with granulocyte colony-stimulating factor (G-CSF) was accepted by the FDA and granted priority review for the prevention of chemotherapy-induced neutropenia (CIN), according the company responsible for developing the agent, BeyondSpring, Inc.

This designation from the agency was based on data from the pivotal phase 3 PROTECTIVE-2 trial (NCT03294577) of plinabulin plus pegfilgrastim versus pegfilgrastim alone to mitigate neutropenic effects of docetaxel, doxorubicin, and cyclophosphamide (TAC).

“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,” Lan Huang, co-founder, CEO, and chairwoman of BeyondSpring, said in a press release. “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 NCCN 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 U.S. annually.”

Data from over 1200 patients treated in PROTECTIVE-2 and 5 supportive trials were considered. In the randomized, double-blind, controlled global trial, the plinabulin arm had superior CIN benefit versus pegfilgrastim alone in patients with breast cancer who were treated with TAC. The primary end point of improved grade 4 neutropenia in cycle 1 was meet, with patients on plinabulin at 13.6% versus 31.5% with the control (P = .0015).

Additionally, all secondary efficacy and safety measures were met, such as duration of severe neutropenia (DSN) and absolute neutrophil count (ANC) nadir. Other benefits of plinabulin included a reduction in the incidence and severity of febrile neutropenia and resulting hospitalizations.

The combination was also found to be well tolerated versus pegfilgrastim alone, with a greater than 20% reduction in grade 2 treatment-emergent adverse events (TEAEs) and overall benefit to quality of life.

Plinabulin is a novel selective immunomodulating microtubule-binding agent administered intravenously for the prevention of CIN. The therapy stimulates release of the immune defense protein, GEF-H1, leading to antitumor activity by way of maturation of dendritic cells resulting in activation of tumor antigen–specific T-cells as well as a boost in the number of hematopoietic stem/progenitor cells.

Previously, the agent was granted breakthrough therapy designation in 2020 for this indication. The company continues to evaluate plinabulin in combination with various agents, including PD-1/L1 inhibitors, where investigators hope to find an efficacy boost with the combination.

The FDA set a Prescription Drug User Fee Act (PDUFA) target action date for this NDA of November 30, 2021.

Reference

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. https://bit.ly/3fCQuAQ