Neutropenia refers to the reduction of neutrophils, a type of white blood cells that serves as the primary defense against infections. Many types of cytotoxic chemotherapies kill all rapidly dividing cells, which include tumor cells, but also healthy white blood cells. The rates of neutropenia vary widely depending on the type of chemotherapy, disease and patient background, and can range from 7 percent to 65 percent of patients. A majority of chemotherapy-induced neutropenia cases are associated with the first cycle of drug treatment, and the condition can often result in delays of further dosing, dose reductions or early termination of chemotherapy in 10 to 20 percent of patients.
Patients with neutropenia are more susceptible to bacterial infections which could become life-threatening without prompt medical attention. Approximately 20 percent of patients with severe neutropenia develop serious bacterial infections. Unfortunately, the initial signs of these infections can be difficult to detect, because patients who lack an immune response do not show the usual signs of infection, such as inflammation or fever. More than 60,000 patients are hospitalized each year for neutropenia associated with fever, which often can cause serious infections in neutropenic patients. The mortality rate of these patients is between 9 and 18 percent.
Since 1988, only G-CSF has been approved for preventing neutropenia. Due to its side effects, high cost as a biologic drug, and its use restricted until 24 hours after chemotherapy treatment, it is only used in approximately 20% of patients. Even with these limitations, the global market for G-CSF drugs, including biosimilars, in 2015 was over $7 billion.
Plinabulin in Neutropenia
In Phase 2 study (Study 101), Plinabulin reduced severe neutropenia induced by docetaxel from 33% to less than 5%, with a p-value of 0.0003. The Phase 2/3 neutropenia registration program (Study 105 and Study 106) targets solid tumor patients who have been previously treated with docetaxel to prevent febrile neutropenia. Thus, BeyondSpring believes that Plinabulin may enable more patients to continue on full dose chemotherapy for a longer period of time, reducing the incidence and severity of neutropenia, which would lead to fewer hospitalizations, improve quality of life, and potentially reduce the mortality rate associated with severe neutropenia.
BeyondSpring also believes that Plinabulin holds numerous potential advantages over G-CSF for the treatment of chemotherapy-induced neutropenia, including acting additionally as an anti-cancer agent, dosing 30 minutes after chemotherapy use and an enhanced safety profile, including a lower incidence of bone pain, which can be seen in up to 20% of G-CSF patients versus 4% among Plinabulin patients.