FDA grants Pfizer ALK / ros1 inhibitor loratinib breakthrough drug qualification

Source: Sina pharmaceutical 2017-04-28 the new generation of ALK / ros1 tyrosine kinase inhibitor (TKI) loratinib from Pfizer, a US pharmaceutical giant, recently received good news from US regulators The U.S Food and Drug Administration (FDA) has awarded loratinib a breakthrough drug qualification (BTD) for patients with anaplastic lymphoma kinase (ALK) - positive metastatic non-small cell lung cancer (NSCLC) who have previously received one or more ALK inhibitors but have progressed Breakthrough drug qualification (BTD) is a new drug review channel established by FDA in 2012 It aims to accelerate the development and review of new drugs for the treatment of serious or life threatening diseases and there is preliminary clinical evidence that the drug can substantially improve the condition compared with existing treatment drugs The drugs that obtain BTD can receive more close guidance, including FDA senior officials, during the research and development, so as to guarantee to provide patients with new treatment options in the shortest time The FDA grants loratinib a breakthrough drug qualification based on the efficacy and safety data of an ongoing phase I / II clinical study This study included a group of ALK positive non-small cell lung cancer (NSCLC) who had previously been treated with one or more ALK inhibitors but had progressed In addition, crown (nct03052608), another phase III clinical study, has recently begun to recruit patients This study is an open label, randomized, two group study, which was carried out in patients with ALK positive metastatic NSCLC It investigated the efficacy and safety of loratinib compared with Pfizer's own marketed oral targeted anticancer drug xalkori (crazotinib, czotinib) for first-line treatment Details of the study can be found at www.clinicaltrials.gov Globally, lung cancer is the leading cause of cancer death It is estimated that non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancer cases Although important progress has been made in clinical treatment, NSCLC is still a difficult disease to treat, especially metastatic NSCLC It is estimated that about 57% of NSCLC patients are metastatic or advanced at the time of diagnosis, and the 5-year survival rate is only 5% NSCLC can be further divided into different subtypes according to tumor histology, molecular biology and other factors ALK gene rearrangement is an abnormal gene change, which will drive the occurrence of lung cancer in some patients The progression of disease is still a great challenge in the clinical treatment of ALK positive metastatic NSCLC because the tumor may acquire additional mutations during the treatment Epidemiological studies show that ALK positive lung cancer accounts for 3% - 5% of all NSCLC cases Ros1 gene rearrangement is another abnormal gene change, which occurs when ros1 gene merges with another gene and changes the normal function of each gene, which may drive the growth of cancer cells Epidemiological data show that the incidence of ros1 gene rearrangement in NSCLC is about 1% It is estimated that there are 1.5 million new NSCLC cases every year in the world, of which about 15000 cases may be driven by carcinogenic ros1 gene rearrangement Ros1 rearrangement defines a different subtype of NSCLC, which may be sensitive to ros1 kinase inhibitors Loratinib is an experimental new generation of ALK / ros1 tyrosine kinase inhibitor (TKI) According to the data of preclinical study, loratinib has a strong therapeutic effect in lung cancer model with ALK and ros1 gene rearrangement Loratinib is specifically designed to inhibit tumor mutations that lead to resistance to other ALK inhibitors and can cross the blood-brain barrier In patients with ALK positive NSCLC, the brain is a common site of metastasis Loratinib is an experimental drug, which has not been approved by any regulatory authorities for any indication Pfizer xalkori: the world's first ALK inhibitor, a model of precision medicine xalkoi (crizotinib, czotinib) is a small molecule tyrosine kinase inhibitor (TKI) targeting anaplastic lymphoma kinase (ALK), ros1 and met, which was approved by FDA in 2011 for the first-line treatment of ALK positive non-small cell lung cancer (NSCLC) The drug is the first ALK inhibitor approved for marketing in the United States, the European Union, China and Japan At present, xalkori has been approved by more than 90 countries in the world, and it is a first-line standard drug for the treatment of ALK positive advanced NSCLC The marketing of the drug has greatly changed the clinical treatment of advanced NSCLC with ALK positive In March and September last year, xalkori was approved by the United States and the European Union for the treatment of adult patients with ros1 positive advanced non-small cell lung cancer (NSCLC) This approval makes xalkori the only targeted anticancer drug driven by biomarkers in the treatment field of ros1 positive non-small cell lung cancer Ros1 rearrangement provides xalkori with a second subgroup of patients who are treated effectively Xalkori's clinical development in this patient group is another example of Pfizer's efforts to identify patients through biomarkers (ros1 rearrangement) and then carry out precision medicine (compiled by Sina pharmaceutical / newborn) article reference source: Pfizer's next-generation ALK / ros1 initiator, loratinib, expanded breakthrough strategy design from FDA for alk-positioning medical non-small cell lung cancer