Self Renew column, F-627 of Efan Medicine.

On June 29, Yifan announced that the second international phase III clinical trial of long-acting G-CSF project f-627 reached the preset clinical endpoint; on July 8, the company further announced that the neutralizing antibody test result of f-627 was negative, that is, low immunogenicity.so far, the clinical trials of f-627 at home and abroad have been successful, and will enter the stage of listing and declaration.in this article, we briefly summarize the relevant situation of the drug and make a rough judgment on its prospect.the long-term "Shengbai drug" chemotherapy is a routine treatment or even a first-line treatment for many cancer patients.chemotherapeutic drugs can seriously damage the immune cells (including granulocytes) of patients due to their undifferentiated cytotoxic effects, resulting in weak innate immune system and easy infection.and G-CSF (granulocyte colony stimulating factor) has the function of stimulating myeloid cells and granulocyte formation, and has the potential to help patients recover the immune system. Therefore, G-CSF has been developed for a long time to alleviate the side effects of chemotherapy induced neutropenia and the so-called "white drug".generally, the decrease in the number of granulocytes starts from 24-72 hours after chemotherapy and reaches the most serious level at 10-14 days.therefore, it is necessary to develop recombinant G-CSF and strive to maintain the number of granulocytes during the two weeks.the earliest recombinant G-CSF was filgrastim of Amgen, which was first approved by FDA in 1991.filgrastim needs subcutaneous injection once a day for 2 weeks, which belongs to short acting G-CSF.in 2002, Amgen launched a long-term version of G-CSF, namely pegfilgrassim (trade name neulasta). The molecule of the drug is formed by fusion of monomethoxypolyethylene glycol (about 20 kDa) at the N-terminal methionine residue of filgrastim.the modification of polyethylene glycol reduces the renal clearance, cell uptake and protease degradation of filgrastim, thus increasing the half-life of filgrastim in vivo.clinical results show that pegfilgrassim can be injected once in a chemotherapy cycle (about 21 days), realizing long-term effect.as a result, pegfilgrassim becomes the standard second generation (long-term) G-CSF.from the global "raw white drug" market, in 2013, the share of long-acting G-CSF was about 76%, and the rest was short-acting G-CSF; by 2018, long-acting G-CSF had occupied more than 90% of the market share.and in China, the long-term G-CSF is also rapidly expanding after 2017.it can be seen that long-term G-CSF is an inevitable trend to replace short-acting G-CSF. however, it is estimated that there is still room for expansion in the overall market of "shengbaiyao". features and market prospects of f-627, a fusion protein of G-CSF and FC, is independently developed by the company's di kinetm bimolecular technology platform. in this molecular structure, G-CSF forms divalent molecules through the disulfide bond in Fc region, and achieves long-term effect. according to the head-to-head test results of f-627 and neulasta, the primary and secondary endpoints of f-627 have been achieved, and the overall effect and safety are not inferior to neulasta, that is, "non inferior". at present, the long-acting G-CSF already on the market in the United States is in addition to the original research drug neulasta of Amgen, and biological similar drugs developed by mylan, coherus and Sandoz. time to market sales of drug molecular R & D enterprises neulasta original research pegfilgratim Amgen 2002 US $3221 million mylan June 2018 (FDA) - udenycapegfilglastim analogues coherus November 2018 (FDA) - ziextenzopegfilgrassim analogues Sandoz November 2018 (EMA), November 2019 (FDA) - biologically similar drugs themselves are far from complex Far more than small molecule generic drugs, combined with the special law and payment environment in the United States, it is not easy to obtain the approval of biosimilars in the United States. it may be mainly for this reason that Dr. Huang Yuliang redesigned the structure of long-acting G-CSF molecule, bypassing the difficult road of development, application and promotion of biologically similar drugs, and hoped to make new drugs with better effect than the original drugs through micro innovation (naturally, the establishment of two Fc fusion proteins is obviously directly related to Dr. Huang's previous background). because the final clinical trial results show that f-627 is only "non inferior" relative to neulasta, the market prospect of f-627 in the United States is uncertain. according to the small edition, combined with the differentiation of f-627 and the average market share of biological similar drugs in the United States, the peak foreign sales of f-627 can be conservatively estimated at 1 / 10 of the peak sales of neulasta (about 4.7 billion US dollars), that is, about 500 million US dollars. and in China, the long-term G-CSF that has been listed at present include xinruibai of Qilu pharmaceutical, jinyouli of Shiyao group and aido of Hengrui Pharmaceutical (i.e. "19K"). drug xinruibaijin Youli aiduo f-627 launched in 2016, 2012 and 2019 in the enterprise Qilu Pharmaceutical Group Hengrui Yifan Pharmaceutical (Jianneng long) molecular structure pefegetine pefeggestin thiopeiferogesin g-csf-fc fusion protein key clinical trials and short-acting G-CSF comparison - compared with short-acting G-CSF and neulasta (long-acting G-CSF), the patients were treated with TAC / Ta chemotherapy Patients with breast cancer, or docetaxel / paclitaxel plus carboplatin regimen for non-small cell lung cancer - 331 breast cancer patients received 4 cycles of neoadjuvant / adjuvant chemotherapy of anthracycline + paclitaxel / anthracycline + cyclophosphamide; 126 patients with lung cancer received 4 cycles of docetaxel + carboplatin / docetaxel + cisplatin, 393 patients with stage I-III invasive breast cancer, End point: duration of grade 3-4 neutropenia in the first cycle of chemotherapy primary end point: duration of grade 3-4 neutropenia in the first cycle of chemotherapy; secondary end point: incidence of severe (grade 4) neutropenia in the first cycle of chemotherapy; secondary end point: incidence of severe (grade 4) neutropenia in the first cycle of chemotherapy; and The primary end points included the duration of severe (grade 4) neutropenia in the first cycle of chemotherapy; the secondary end points: the incidence of severe (grade 4) neutropenia in the first cycle of chemotherapy; the incidence of febrile neutropenia (FN) during the whole course of chemotherapy; the use rate and days of intravenous antibiotics; the hospitalization rate and days due to FN and infection It can be seen that f-627 is the only drug in China that has been compared head-to-head with the original long-acting G-CSF and proved to be "non inferior". From the perspective of academic promotion, this drug has obvious advantages. the domestic sales of the other three drugs have increased rapidly in the past three years, among which the sales of jinyouli and xinruibai, the first to be listed, have reached nearly 1.5 billion yuan. combined with the clinical data of f-627, Xiaobian thinks that the domestic peak sales volume of f-627 in the future is from RMB 2 billion. there are external invaders? On June 15, Wanchun pharmaceutical announced that the interim analysis of phase 3 clinical trial of protective-2 (nct03294577), an innovative drug, reached the main end point. the indication of this clinical trial is chemotherapy-induced severe neutropenia (CIN). the specific design of this clinical trial was to compare the efficacy of 40 mg of pranabarin combined with 6 mg of long-acting G-CSF (neulasta) versus 6 mg of long-acting G-CSF monotherapy in breast cancer patients receiving TAC regimen (docetaxel, doxorubicin and cyclophosphamide). therefore, in this experiment, punabilin is only an auxiliary role, which will only promote the large-scale of long-term G-CSF rather than compete with it in the current market. however, Wanchun Pharmaceutical Co., Ltd. is also carrying out the detection of the granulocyte protection effect of pranabarin monotherapy: in addition, in the protective-1 test, Wanchun is also conducting head-to-head comparison between punabilin and pegfilgrassim. it can be seen that punabilin is likely to invade the G-CSF market in the future. the success of the international clinical trial of f-627 is a milestone event, which makes it expected to become the first truly innovative biological drug to go abroad and create history together with zebotinib. at the same time, if f-627 is approved successfully in the future, the potential sales of domestic and foreign countries are conservatively estimated to be no less than 5.5 billion yuan, which is equivalent to creating another 100 million sails. please contact wechat: wz910605 business cooperation contact: welcome to forward and share. 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