Beyond Spring announced that its "first-in-class" new drug plinabulin (plinabulin) is used in the Phase 3 clinical trial of PROTECTIVE-2 (106 study) for severe neutropenia (CIN) caused by chemotherapy The mid-term analysis of the trial reached the main study endpoint. According to the announcement of Wanchun Pharmaceutical: the remarkable mid-term results of the study are the first breakthrough in the treatment standard and clinical benefit of CIN indications in 30 years!
Neutrophils are white blood cells and are the main means of fighting infection. Statistics show that neutropenia affects 7% to 65% of patients receiving chemotherapy. Patients are more susceptible to bacterial infections, of which approximately 20% of patients with severe neutropenia develop severe bacterial infections. More than 60,000 patients are hospitalized each year for neutropenic fever, which often leads to serious infections in patients with neutropenia. Since 1988, only G-CSF has been approved to prevent neutropenia. Due to its side effects (such as bone pain) and the high cost of being a biopharmaceutical, its use is limited and is only used in about 20% of patients.
Purnabulin is an activator of guanine nucleotide exchange factor (GEF-H1), which can destroy the microtubule network in the cytoskeleton and release GEF-H1. This process activates the downstream signal transduction pathway, leading to the activation of protein c-Jun. Activated c-Jun enters the nucleus of dendritic cells, up-regulates immune-related genes, and then activates a series of related genes to promote dendritic cell (DC) maturation, T cell activation, and prevent neutropenia. In addition, Punabulin is also a non-G-CSF agent, which reverses the formation of neutrophils induced by docetaxel in the bone marrow and maintains neutrophil levels within the normal range, with a different The mechanism of G-CSF prevents CIN. It has been shown in preclinical studies that punabrin can prevent neutropenia caused by chemotherapy drugs with different antitumor mechanisms.
The international multi-center phase 3 clinical study called PROTECTIVE-2 conducted by Wanchun Medicine is to compare 40mg puna in breast cancer patients treated with chemotherapy TAC regimen (docetaxel, doxorubicin and cyclophosphamide) Brin combined with 6mg long-acting G-CSF (neulasta) treatment and 6mg long-acting G-CSF monotherapy. This mid-term data analysis included data from approximately 120 patients.
The results showed that in the main study endpoint "percentage of patients with grade 4 neutropenia that did not occur in the first chemotherapy cycle", combination therapy with punabrine was significantly better than long-acting G-CSF monotherapy ( p<0.01).
In terms of the key secondary endpoints, both "the duration of grade 4 neutropenia (DSN days) within 8 days before the first chemotherapy cycle" and "DSN within the first chemotherapy cycle" reached significant significance, confirming The Punabulin combined group can play the role of neutrophil protection in the first 8 days, which can provide comprehensive protection.
"This is exciting data, which not only shows very significant statistical significance, but also has important clinical significance." said Douglas Blayney, Ph.D., a professor of medicine at Stanford School of Medicine and a global principal investigator of CIN research in Punablin: " At present, the medical needs of CIN are far from being met, so there is still an urgent need for new therapeutic drugs, especially drugs with a different mechanism than the existing standard therapeutic drug G-CSF.' Grade 4 neutrophils did not occur in the first chemotherapy cycle The percentage of patients with reduction syndrome is the main research endpoint used in the CIN field for the first time, and I also hope that this endpoint will become a new treatment evaluation standard for CIN in the future."
Dr. Huang Lan, Chairman and Co-founder of Wanchun Medicine, added: "The remarkable mid-term results of the PROTECTIVE-2 study are the first breakthrough in the treatment standard and clinical benefit of CIN indications in 30 years." In addition The combination of Punabrin and G-CSF has the potential to prevent infection and hospitalization, which is particularly important for doctors, patients, and healthcare systems in the COVID-19 pandemic.
In China, the State Food and Drug Administration approved Punablin’s two phase 2/3 registration clinical trial applications (project numbers 105 and 106) for the prevention of chemotherapy-induced neutropenia. According to the drug clinical trial registration and information disclosure platform, there are 6 clinical studies carried out by Punabulin registration, including two phase 3 international multi-center clinical studies.
Wanchun Pharmaceutical is a global biopharmaceutical company in clinical stage. It was listed on NASDAQ in 2017, focusing on the research and development of new cancer therapies.