In the CRL, the FDA indicated that the single registrational trial (106 Phase III) did not provide sufficient proof of efficacy to demonstrate benefit.
BeyondSpring CEO Dr. Lan Huang, Ph.D./Courtesy BeyondSpring Pharmaceuticals
It was not an auspicious start to December for BeyondSpring Pharmaceuticals, which received a Complete Response Letter (CRL) from the U.S. Food and Drug Administration requesting another trial before its combination drug for chemotherapy-induced neutropenia (CIN) could be approved.
Plinabulin, the New York-based biopharma company’s lead asset, is a selective immunomodulating microtubule-binding agent (SIMBA) which induces antigen-presenting cells (APC). It triggers the release of GEF-H1, an immune defense protein, thereby offsetting the development of the abnormally low levels of neutrophils – white blood cells – that define CIN. This also gives the drug its case for being an effective treatment for non-small cell lung cancer (NSCLC), for which it is currently being studied in Phase III in combination with docetaxel.
CIN, which is a common side effect particularly in lung cancer patients, can lead to infections and cause treatment delays as it limits the dosing of cytotoxic agents. In September 2020, plinabulin received Breakthrough Therapy Designation from both the FDA and China’s Center for Drug Evaluation (CDE) for the prevention of CIN.
In the CRL, the FDA indicated that the single registrational trial (106 Phase III) did not provide sufficient proof of efficacy to demonstrate benefit and that a second well-controlled trial would be required to satisfy the burden of evidence in this indication.
The New Drug Application (NDA) submitted in June 2021 for plinabulin in combination with granulocyte colony-stimulating factor (G-CSF), included data from a pivotal Phase III PROTECTIVE-2 study, which showed that the drug combination met the primary endpoint in Cycle 1, improving prevention of grade 4 neutropenia from 13.6% to 31.5%. The trial also hit all key secondary endpoints, which included the duration of severe neutropenia and absolute neutrophil count (ANC) nadir. This data was submitted along with five supportive trials of over 1200 patients.
BeyondSpring Co-founder, CEO and Chairwoman Dr. Lan Huang, Ph.D. reacted to the news in a statement:
“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,” she said. “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 company added that it remains confident in plinabulin’s efficacy and safety data in the CIN indication.
BeyondSpring said it expects to work closely with the FDA to discuss a possible future clinical path for plinabulin in CIN, and noted that this may include a second study.
In August, BeyondSpring announced positive topline results for plinabulin in combination with docetaxel to treat second and third-line NSCLC. Compared with docetaxel alone, the combination met the primary endpoint of increasing overall survival and led to a significant reduction in the incidence of Grade 4 neutropenia. At the time, Huang said that the company planned to submit an NDA to the FDA for plinabulin in this indication in the first half of 2022.
