NSCLC and Neutropenia Prevention
BeyondSpring’s lead oncology asset, Plinabulin, is in a Phase 3 trial in non-small cell lung cancer (NSCLC) treatment and initiating a Phase 3 trial in the prevention of Docetaxel-induced Neutropenia. In addition, Plinabulin will be tested in combination with Nivolumab in NSCLC in a Phase 1b/2 study. Plinabulin has been granted composition and usage patents in 35 countries, including the U.S, E.U., Japan and China. Its new patents protect the asset to 2036.
In preclinical studies, Plinabulin has shown favorable safety and anti-tumor activity in a variety of cancer models, including brain tumors and KRAS mutant tumors, demonstrating its potential efficacy across a broad spectrum of cancers, including gastrointestinal, breast, ovarian, prostate and hematological cancers.
Plinabulin has been given to over 140 patients to date through now completed Phase 1 and 2 trials. It has proven to be well-tolerated and shown encouraging anti-tumor activity. Based on consultation with the U.S. FDA, BeyondSpring is conducting an ongoing single, large global Phase 3 pivotal trial for second- and third-line NSCLC. The global study is taking place in the U.S., other western countries and China.
Plinabulin will also be evaluated in a Phase 3 pivotal trial for Neutropenia prevention in patients who have Docetaxel-approved indications.
According to the National Cancer Institute, an estimated 221,200 cases of lung cancer are diagnosed in the United States annually, of which NSCLC accounts for approximately 87 percent of all lung cancer cases. The prognosis for patients with lung cancer is poor, with five-year survival rates of only 17.4 percent. Lung cancer is the leading cause of cancer death in the United States, and on a global basis, 1.8 million cases of lung cancer are diagnosed annually. China represents one-third of lung cancer patients globally, with approximately 700,000 cases diagnosed in China in 2015. Despite the availability of multiple drugs to treat NSCLC, there remains a great need for novel therapies in NSCLC, which is projected to be a $28 billion market by 2020.
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 not only tumor cells but also healthy white blood cells. The rates of Neutropenia vary widely depending on the type of chemotherapy, disease and patient background but range from 7 percent to 65 percent of patients. More than half of the cases of chemotherapy-induced Neutropenia are associated with the first cycle of drug treatment. Chemotherapy-induced Neutropenia leads to 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 and, without prompt medical attention, this condition can become life-threatening. 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 effect, high cost as a Biologic, and lack of ease of use as it has to be given 24 hours after chemotherapy use, it is only used in 20% patients. Even with small reach of patients, its sales in the US alone in 2015 is over $5.7 billion.