Cure rate 100%? How "god" is this new crown oral drug?

Text/Cow Lotus

On February 25, Japan's Shiono Yoshi pharmaceutical Company announced that it has completed the analysis of the phase II .b clinical trial of the new crown oral drug S-217622 (internal research and development number), and has applied to the Japanese Ministry of Health, Labor and Welfare for a production and sales license. Source: ANN News

A few days ago, a Japanese pharmaceutical company announced that it has completed the analysis of the phase II .b clinical trial of the new crown oral drug S-217622 (internal research and development number), and has applied to the Japanese Ministry of Health, Labor and Welfare for a production and sales license.

According to Japanese media reports, according to the intermediate results of the final trial, more than 90% of people who did not detect infectious viruses after 3 days of treatment with the drug. In its application, the pharmaceutical company wants to apply a "conditional early approval system," which allows commercialization until the final trial is completed.

Founded in Osaka in 1878, the pharmaceutical company named Yoshishi Shiono is Japan's fifth-largest pharmaceutical company and owns Xofluza, a "super flu drug" developed with Roche. In March 2020, Ping An Life, a subsidiary of Ping An of China, invested in Yoshio Shiono Pharmaceutical and became an important strategic shareholder of ping an enterprise.

China News Weekly noted that there have been a number of domestic media reports that the cure rate of this new crown oral drug has reached 100%, which has aroused great concern and controversy.

Cure rate 100%?

The new crown oral drug S-217622, which has received widespread attention this time, jointly researched and developed by Hokkaido University and Shiono Pharmaceutical Company, is a 3CL protease inhibitor. 3CL protease (also known as primary protease) is a protease that cuts and processes RNA in the virus's own code, and its inhibition prevents the formation of replication-essential enzymes, such as RNA-dependent RNA polymerase, thereby inhibiting viral replication.

Clinical trials of S-217622 are primarily aimed at mild/moderate patients. In July last year, Shiono Pharmaceutical Company began Phase I clinical trials. On September 27 of the same year, the company conducted Phase II/III clinical trials.

On February 7 and 25 this year, Shiono Pharmaceutical Company announced the results of Phase II.a and II.b trials of Phase II./III. clinical trials. According to the experimental data of Phase II.A, compared with the placebo group, the viral titer and RNA were significantly reduced; after 3 days of continuous drug administration (day 4), the positive ratio of viral titer decreased by 63% (low-dose group) and 80% (high-dose group), respectively; the median time of viral titer negative was shortened by 2 days. In terms of efficacy, all patients taking S-217622 did not develop the need for hospitalization, while 14.3% (2/14) of patients in the placebo group required hospital admission.

It is worth noting that according to the Phase II.A antiviral and safety results shown in the Research Report of Guojin Securities, on the 6th day of nucleic acid testing, the test results of patients taking low-dose S-217622 were all negative (

"That's not a good idea." A domestic virologist said in an interview with China News Weekly that most of the current infected people are mild or even asymptomatic, and what the so-called "100%" refers to remains to be defined.

The virologist further explained, "Now that many patients can't detect the virus on the fifth day even if they don't take medicine, is it possible to say that drinking tap water will also have a 100% cure rate?" ”

It is reported that the Phase II .b trial was a randomized, placebo-controlled, double-blind study, in order to confirm the antiviral effect and clinical symptom improvement after 5 days of oral administration, 428 mild to moderate patients (419 in Japan and 9 in South Korea) were enrolled, mainly in those infected with the Omi kerong variant. Patients take the drug orally once a day for 5 consecutive days.

The results showed that after 3 days of continuous administration (i.e., the 4th day), the titer of the new coronavirus decreased rapidly compared with the control group, and the positive rate of viral titer in the treatment group was less than 10%, and the decrease was greater than that of stage II.a. However, from the start of administration to 120 hours (day 6), the 12 symptoms had a tendency to improve overall, but did not reach the primary endpoint (the level of viral titer decreased in the drug group compared to the placebo group at each time point).

"The sample size is small, and there is no more convincing evidence." Some medical sources pointed out that determining whether a drug has a therapeutic effect on a disease also requires a large sample of multicentre randomized double-blind trials, while only a few hundred people in the aforementioned trials cannot achieve the concept of large samples.

Shi Lichen, a medical expert, analyzed to China News Weekly that according to the latest domestic "Diagnosis and Treatment Plan for Novel Coronavirus Pneumonia (Trial Ninth Edition)", the cases were classified and treated. Among them, only centralized isolation management is implemented for mild cases, and there is no mention of treatment.

He believes that "this trial is mainly aimed at mild/moderate patients, and from this point of view, the market value of this drug is not large." ”

It is understood that Shiono Yoshi Pharmaceutical Company has completed the commercial production of the first batch of S-217622, and plans to reach a production capacity of more than 10 million copies per year after April. At the same time, the company is planning to accelerate the phase III study of mild and moderate patients, with a target of 1260 subjects. Phase II.b/III clinical trials in asymptomatic or only mildly symptomatic patients will also be accelerated, targeting 300-600 subjects.

At present, two oral COVID-19 drugs approved for clinical treatment in Japan are from Merck and Pfizer in the United States. If the subsequent S-217622 is approved, this drug will become the first domestic new crown oral drug in Japan.

It is worth mentioning that the advent of japan's new crown oral drug has also pushed the stock prices of domestic Peking University Pharmaceutical, Yangtze River Health and other companies to a limit.

In the past two days, Peking University Pharmaceutical and Yangtze River Health have issued stock price change announcements in response to relevant rumors.

Peking University Pharmaceutical responded that the company has never carried out the research and development of new crown special drugs, nor has it discussed cooperation with Yoshinoshi Shiono in Japan on cooperation with new crown special drugs. Changjiang Health said that at present, the company has reached a cooperation with Chang'ao Pharmaceutical Technology Group Co., Ltd., a subsidiary of Yanyeyi, on the "Lulite" luriconazole cream and is responsible for product sales. At present, the two sides have not cooperated on the treatment of new coronavirus drugs.

A number of pharmaceutical companies have entered the market

As of March 16, the cumulative number of confirmed COVID-19 cases worldwide exceeded 460 million, and the cumulative number of deaths exceeded 6 million. This is the pandemic with the highest average annual fatality experienced by humanity in the past 100 years.

While the world has increased investment in research and development, the rate of mutation of the new crown virus has not slowed down, and even accelerated in the spread of mutation, from alpha, beta, gamma, delta, to now the global spread of Themi keron.

The Omikeron includes the three main lineages of BA.1, BA.2, and BA.3. A study in Japan showed that since January this year, the spectrum frequency of BA.2 has increased and surpassed BA.1 in several countries such as the Philippines, India, Denmark, Singapore, Austria and South Africa, making it more contagious. The U.S. Centers for Disease Control and Prevention said on March 15, local time, that as of March 12, the infection cases of the BA.2 evolutionary branch of the Omicron variant are expected to account for 23.1% of the existing infection cases of the new coronavirus variant in the United States. In China, the BA.2 strain is responsible for the recent increase in cases.

In addition, news of the reorganization of Delta and Omicron was recently confirmed by a French study and by WHO.

Under such circumstances, the approval speed and research and development progress of new crown oral drugs at home and abroad are accelerating.

In December 2021, Pfizer's Paxlovid was authorized for emergency use by the U.S. Food and Drug Administration (FDA), a two-part combination of nematvir (a 3CL protease inhibitor) and a low-dose ritonavir. On January 20 this year, Merck's ORAL COVID-19 drug, molnupiravir, allowed 27 generic drug companies to produce and supply to 105 low- and middle-income countries.

On February 11 this year, the State Food and Drug Administration approved Paxlovid for the treatment of mild to moderate coronavirus pneumonia patients who may develop severe disease. Ma Shuai, an analyst at Anxin Securities, believes that this approval shows the importance that domestic regulators attach to new crown oral drugs, and the development of domestic new crown oral drugs is expected to accelerate.

In fact, many domestic pharmaceutical companies have laid out a number of oral anti-new crown drugs.

According to Huachuang Research And Research Report, the "azifedine (oral)" of real organisms is in the clinical phase III stage; the "VV116 (oral) (oral)" of Junshi Biology/Wangshan Wangshui/Chinese Academy of Sciences has started clinical Phase II/III research; the oral 3CL inhibitors of Celega Pharmaceuticals, Simceree Pharmaceutical, Zhongsheng Pharmaceutical, Junshi Biologics and other companies are in the preclinical research stage and are expected to enter the clinic in the next 6 months.

On the evening of March 15, the National Health Commission issued the "Diagnosis and Treatment Plan for Novel Coronavirus Pneumonia (Trial Version 9)" (hereinafter referred to as the "Diagnosis and Treatment Plan"), which further standardized antiviral treatment. The "Diagnosis and Treatment Plan" writes two specific anti-new coronavirus drugs approved by the State Food and Drug Administration into the diagnosis and treatment plan, namely nematvir/ritonavir (Paxlovid) and domestic monoclonal antibodies (amphavir monoclonal antibody/romimab injection).

The latter is a new crown special injection drug developed in the mainland. Existing clinical studies have shown that this antibody combination can reduce hospitalization and mortality by 80%.

"It still depends on the degree of infection these new crown oral drugs are for, if only asymptomatic or mild patients, the market value of such drugs is not large." Because for non-severe patients, without involving drug therapy, the physical condition will gradually improve over time. Shi Lichen said that the influence of new crown oral drugs on the domestic market may be limited, and the focus of development is on overseas markets.