The first-line treatment of squamous NSCLC with drug K + chemotherapy was approved in China

On November 26, the official website of the National Drug Administration (nmpa) showed that another indication of keytruda (acceptance No jxss1800025) was approved, and the first-line treatment of metastatic non-small cell lung cancer (NSCLC) was combined with chemotherapy (carboplatin and paclitaxel) This indication does not need to consider the expression of PD-L1 in patients In July 2018, March 2019 and September 2019, pablizumab was approved in China for the indications of unresectable metastatic melanoma treated with single drug, non scaly NSCLC treated with first-line combination chemotherapy, and PD-L1 positive (TPS ≥ 1%) NSCLC treated with first-line single drug So far, the indications of first-line treatment of NSCLC with K medicine have reached 3 in just 8 months, becoming the most approved PD-1 monoclonal antibody in the field of advanced lung cancer treatment in China Indications of drug K approved in China In the U.S market, the three first-line indications of K medicine in the treatment of NSCLC made Hummer credit for K medicine's "king of immunity" Looking back the sales curve of k-drug from 2015 to now, it is not difficult to find that there are two "acceleration" inflection points of k-drug in 2016q4 and 2017q2, which are brought by the fact that k-drug is accelerated by the FDA of the United States to be approved for the first-line treatment of PD-L1 high expression (TPS ≥ 50%) NSCLC (based on the keynote-024 study) and the first-line treatment of non scaly NSCLC (based on the keynote-021g study) combined with chemotherapy These two conditionally accelerated approved indications are the two key "milestones" for the final anti superoxide drugs in 2018q2 In October 2018, FDA approved the first-line treatment of squamous NSCLC with k-drug combined with chemotherapy based on keynote-407 study Single quarter sales trend of four PD-1 / PD-L1 McAbs during q1-2019 In terms of sales, the sales volume of K drugs in the first three quarters of 2019 totaled US $7.973 billion, which is expected to exceed US $11 billion this year (i.e the fifth year of listing), while the first-line treatment market for advanced lung cancer contributed more than 65% of the sales volume of K drugs in the first three quarters It is undeniable that the clinical research behind the three indications (keynote-189, keynote-407 and keynote-042) of "harvest" of K medicine has made great contribution to the achievement of K medicine today They are like the pearl inlaid in the crown of "king of immunity" of K medicine, bringing them bright and light Six monoclonal antibodies have been approved for listing in China, and AstraZeneca and Roche's monoclonal antibodies of PD-L1 will soon be welcomed The competitive pressure of K drug is no less than that of American market In response to how to deal with domestic PD-1 in the Chinese market, MSD's global management believes that in the field of tumor immunotherapy, we still need to rely on data to speak, and the reason why drug K has become the "king of immunity" depends on its relatively convincing clinical data, especially its advantages in total survival (OS) treatment On June 20 this year, MSD held investor day again after many years During this period, MSD management demonstrated the excellent OS data obtained by K medicine in a series of tumor species, and conveyed a momentum of "who gives up" to the outside world OS data in the clinical study of single or combined treatment of all kinds of malignant tumors with drug K On June 11, 2019, the U.S FDA approved drug K as a single drug for the first-line treatment of PD-L1 positive (CPS ≥ 1) recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), and combined chemotherapy for the first-line treatment of all recurrent or metastatic HNSCC population (without considering the expression of PD-L1) The number of first-line treatment indications approved for drug K in the United States has reached 8 (including conditional acceleration of approved indications), ranking first among all PD-1 / PD-L1 immunosuppressive checkpoint inhibitors K drug's market performance in China is also worthy of the expectations of MSD's global management Within one year after the commercial launch in September 2018, K pharmaceutical achieved sales of 2 billion yuan This number has created the history of prescription drugs in China At the same time, with the successful performance of K drug in the domestic market, MSD China's growth rate in Q1, Q2 and Q3 of this year reached 67%, 41% and 90% respectively, all of which became MSD's fastest growing market in the world in the current quarter 2019 Q3 MSD China leads all MSD markets with 90% growth rate Several investment consulting institutions predict that k-drug will become the largest product in the global prescription drug market in 2025, replacing Sumeria to become the "king of drugs" in the world There is no doubt that the Chinese market is crucial for the future growth of k-drug But is building a "data wall" enough to push the K drug up? Are the three pearls on the "crown" of K medicine enough to illuminate the future of K medicine in China and bring it a bright future? Every year, there are about 780000 new lung cancer patients in China, of which nearly 660000 (85%) are non-small cell lung cancer (NSCLC), about 400000 (60%) have developed advanced or metastatic lung cancer, and about 30% are squamous NSCLC; among non squamous NSCLC patients, about 60% are non driven gene mutation, about 170000 As the only PD-1 mAb approved for first-line treatment of advanced NSCLC in China, drug K has a huge market and growth space However, the market of lung cancer in China is different from that in Europe and America In the world, k-drug only needs to have positive PK clinical data with several competing products; however, in China, k-drug has several domestic PD1 competitors Although they have not been approved for lung cancer indications at present, they have temporarily given k-drug loose market space, but lung cancer indications are necessary for each company, and in the future, only from the number of competing products, it will be more intense than the international market In addition, K drug should not only have PK data with domestic PD1 drug, but also PK price Although K medicine has a long first mover advantage in China's lung cancer market, it is not clear whether it can thrive in such a living environment and stand out from the rest to continue its brilliance In just five years, drug K has been approved in the United States for 15 tumor species, 22 (without conditionally accelerated indications) indications (covering 15 different tumor species such as melanoma, small cell lung cancer, non-small cell lung cancer, squamous cell carcinoma of the head and neck, gastric cancer, esophageal cancer, renal cell carcinoma, endometrial cancer, and all malignant tumors with MSI-H / dmmr) It is inseparable from its huge investment in R & D According to the official data of MSD, more than 1000 clinical studies related to K drugs have been carried out in the world Nature review drugs discovery published an article titled "trends incremental development for PD-1 / PD-L1 inhibitors" on November 4 this year, which shows that there are 873 researches related to K drugs, 315 more than in 2017, and more than 807 of O drugs, which is the "king of clinical research" of PD-1 / PD-L1 immunosuppression point inhibitors Statistics on the number of clinical studies conducted by PD-1 / PD-L1 immunocheckpoint inhibitors in 2017 and 2019 However, in China, if k-drug is to succeed, it cannot stop at the four currently approved treatment indications, but it must "introduce" new indications to China at the fastest speed and obtain approval, which also means that k-drug needs to accelerate its clinical research in China According to the data searched on clinical trials.gov, the number of phase 3 registered clinical studies of K drug in China reached 15 (k drug), surpassing 14 of BMS, but still lagging behind Hengrui (17) and Baiji (16) Statistics of clinical studies on PD-1 / PD-L1 immunosuppressive checkpoint inhibitors in mainland China The competition of PD-1 market, whether in China or in Europe and America, is compared with the number and speed of approved indications In order to keep its "king of immunity" position in China, drug K must be rooted in China, and increase its R & D efforts and progress in China, especially when other imported and domestic monoclonal antibodies against PD-1 / PD-L1 start to "shrink around" The keynote-042 study included 262 Chinese patients, the keynote-407 and Chinese population expansion study included 125 Chinese patients, and the keynote-181 study included 123 Chinese patients In all these studies, there is a common finding that the efficacy data of K drug treatment in Chinese patients seems to be better than that in the whole population However, there is no evidence-based medical evidence for other monoclonal antibodies (mainly imported) against PD-1 / PD-L1 According to the results of the Chinese subgroup and Chinese population expansion study of keynote-042 study, the median total survival (OS) of NSCLC treated with k-drug with different PD-L1 expression was stable at 20 months, and the reduction range of death risk (HR value) was stable at 31% - 38%, while the data of the global population, both OS and death risk, decreased with the decrease of PD-L1 expression (as shown in the figure below) Keynote-042 comparison of Chinese subgroup and Chinese extended study data with global OS data in clinical study Similarly, a comparative analysis of the data of the Chinese subgroup in the keynote-181 study and the data of the global overall study population (see the table below) shows that compared with the data of the overall treatment population, the total survival benefit (OS) of K medicine for the patients with locally advanced or metastatic esophageal cancer in China is more significant, and the range of reducing the risk of death is more significant (45% vs 15%), in the subgroup of PD-L1 positive patients, the median OS of Chinese patients reached one year, which was better than the current first-line chemotherapy program, and the risk of death was twice that of the whole population (66% vs 33%) Keynote-181 comparison of Chinese subgroup and global OS data in clinical study Will drug K be a more suitable PD-1 monoclonal antibody for Chinese patients? This needs more clinical studies on Chinese patients, and the results of K drug clinical studies on tumors with Chinese characteristics (such as liver cell carcinoma, gastric cancer, etc.) to prove.