A new one-off cure for influenza

[product information of China Pharmaceutical network] s-033188, developed by yanye pharmaceutical company of Japan, is a 5-cap-dependent endonuclease inhibitor It is a new clinical drug in research that can inhibit the proliferation of influenza virus in the world The goal of the drug is that flu patients can take it once to suppress flu symptoms within a day Shionogi, a Japanese pharmaceutical company, recently announced that s-033188, a new drug under development to treat influenza, has shown remarkable efficacy in phase 3 clinical trials around the world S-033188 is a novel inhibitor of 5 ′ cap dependent endonuclease activity of influenza virus The results showed that compared with placebo, the time to symptom relief (TTAS) was significantly reduced (P < 0.0001), and other important secondary clinical endpoints (such as virus titer reduction) also achieved positive results Large scale influenza transmission is a major public health problem, and new influenza drugs are urgently needed to improve the current treatment Globally, about 3-5 million serious cases and about 250000-500000 deaths are caused by influenza every year In general, the high-risk groups for influenza complications are children under 2 years old, elderly people over 65 years old, pregnant women and people with specific diseases, including chronic heart disease, lung disease, metabolic diseases (such as diabetes) and people under immunity ▲ the molecular mechanism of cap snapping (photo source: PNAs) because the genome of influenza virus is very small, the synthesis of the required protein depends on the translation system of the host cell Therefore, the messenger RNA (mRNA) of influenza virus needs to have both 5 'cap structure and 3' - poly (a) tail structure which can be recognized by host cell translation system Among them, the 5 'cap structure was "snatched" by the endonuclease activity of PA subunit in RNA polymerase complex of influenza virus This so-called "cap snapping" - the capture of cap like structures of host mRNA for viral mRNA transcription - is necessary for the initiation of influenza virus transcription Because cap snapping is a key link in the replication cycle of influenza virus, and there is no similar mechanism and corresponding protease in the host cell, the inhibitor of cap snapping endonuclease can selectively block the transcription process of influenza virus, while not affecting the host cell Therefore, this mechanism has become a potential target of anti influenza drugs Action mechanism of s-033188 (photo source: Shionogi) s-033188 developed by yanyeyi Pharmaceutical Co., Ltd is a 5-cap-dependent endonuclease inhibitor It is a new clinical drug in the world that can inhibit the proliferation of influenza virus The goal of the drug is that flu patients can take it once to suppress flu symptoms within a day The capstone-1 study was a randomized, double-blind, multicenter, parallel group, placebo-controlled, and active control study involving 1436 influenza A or B patients Patients aged 20 to 64 years were randomly assigned in a 2:1:2 ratio to receive a single dose of 40 or 80 mg of s-033188 (based on body weight), placebo or 75 mg of oseltamivir Patients in the 12-to-19-year-old group were randomly assigned in a 2:1 ratio to receive a single dose of s-033188 or placebo At screening, patients weighing less than 80 kg received 40 mg of s-033188, while patients weighing more than 80 kg received 80 mg of drug Capstone-1's top line results included a significant reduction in TTAS compared to placebo, reaching the primary end point (P < 0.0001) S-033188 and oseltamivir showed similar reductions in TTAS The virus titer decreased significantly in the following days and the period of virus shedding S-033188 was well tolerated The incidence of side effects of s-033188 was similar to that of placebo It should be noted that the incidence of side effects of s-033188 was significantly lower than that of oseltamivir, especially nausea "We are very excited about s-033188, a new cap dependent endonuclease inhibitor," said Dr tsutae den Nagata, Shionogi medical officer "This result confirms the significant efficacy and drug safety we have observed before, and the viral load and duration of virus shedding period are reduced very quickly compared with oseltamivir." According to the results of capstone-1, Shionogi plans to submit a new drug application (NDA) to Japan's PMDA later this year Shionogi is currently conducting another global phase 3 clinical trial (capstone-2) to study the high-risk population of influenza related complications, and patient recruitment is ongoing.