Source: China News Weekly (ID: chinanewsweekly)
Author: Niu He
If only for asymptomatic or mild patients
The market value of these drugs is not large
On February 25, Japan’s Shionogi Pharmaceutical Co., Ltd. announced that it had completed the phase IIb clinical trial analysis of the new crown oral drug S-217622 (internal R&D number), and had applied to the Japanese Ministry of Health, Labour and Welfare for production. License to sell. Source: ANN News
A few days ago, a Japanese pharmaceutical company announced that it has completed the analysis of the Phase IIb clinical trial of the new crown oral drug S-217622 (internal R&D number), and has applied to the Japanese Ministry of Health, Labour 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 were treated with the drug for 3 days had no infectious virus detected. In the application, the drug company hopes to apply a “conditional early approval regime” that would allow commercialization before final trials are completed.
China News Weekly noticed that many domestic media reported that the cure rate of this new crown oral drug reached 100%. This statement has caused great concern and controversy.
100% cure rate?
The novel coronavirus oral drug S-217622, which has received widespread attention this time, was jointly researched and developed by Hokkaido University and Shionogi Pharmaceutical Co., Ltd. It is a 3CL protease inhibitor. The 3CL protease (also known as the main protease) is a protease that cleaves and processes RNA in the virus’s own encoding, 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 focused on mild/moderate patients. In July last year, Shionogi Pharmaceutical Company started a phase I clinical trial. On September 27 of the same year, the company launched Phase II/III clinical trials.
On February 7 and 25 this year, Shionogi Pharmaceutical Co., Ltd. announced the results of Phase IIa and Phase IIb clinical trials of Phase II/III clinical trials. From the experimental data of Phase IIa, compared with the placebo group, the virus titer and RNA were significantly reduced; after taking the drug for 3 days (the 4th day), the proportion of positive virus titers decreased by 63% (low-dose group) and 80%, respectively. % (high-dose group); the median time to negative viral titers was shortened by 2 days. In terms of efficacy, none of the patients taking S-217622 developed the need for hospitalization, compared with 14.3% (2/14) of patients in the placebo group.
It is worth noting that, according to the Phase IIa antiviral and safety results shown by the Sinolink Securities Research Report, on the 6th day of nucleic acid testing, the test results of patients taking low-dose S-217622 were all positive. Negative (
“This statement is not reliable.” A domestic virologist said in an interview with China News Weekly that most of the infected people are mild or even asymptomatic. What exactly “100%” means is yet to be defined.
The virologist further explained, “Now many patients can’t detect the virus on the fifth day even if they don’t take medicine, can it be said that drinking tap water will also be 100% cured. rate?”
It is reported that the Phase IIb trial is a randomized, placebo-controlled, double-blind study. In order to confirm the antiviral effect and clinical symptom improvement after oral administration for 5 days, 428 mild to moderate patients ( Japan has 419 and South Korea has 9) into the group, mainly in people infected with the Omicron variant. The patient took the drug orally once a day for 5 consecutive days.
The results showed that after continuous administration for 3 days (ie, the 4th day), the titer of the new coronavirus decreased rapidly compared with the control group; the positive rate of virus titer in the treatment group was less than 10% , the decline is greater than that in stage IIa. However, from the start of dosing to 120 hours (day 6), the 12 symptom total scores tended to improve, but did not meet the primary endpoint (reduction in viral titers 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 professionals pointed out that to determine whether a drug has a therapeutic effect on a disease, a large sample and multi-center randomization is needed. A double-blind trial, and the aforementioned trial has only a few hundred people, so the concept of a large sample cannot be achieved.
Medical expert Shi Lichen analyzed to China News Weekly that according to the latest domestic “New Coronary Virus Pneumonia Diagnosis and Treatment Plan (Trial Version 9)”, the cases were classified and treated. Among them, only centralized isolation management is implemented for mild cases, and no treatment is mentioned.
He believes that “this trial is mainly aimed at patients with mild/moderate disease, and from this perspective, the market value of this drug is not large.”
It is understood that Shionogi 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 for mild and moderate patients, with a target number of 1,260 subjects. At the same time, the Phase IIb/III clinical trials for asymptomatic or only mildly symptomatic patients will be accelerated, with a target number of 300-600 subjects.
Currently, two oral drugs for COVID-19 approved for clinical treatment in Japan are from Merck and Pfizer in the United States. If the follow-up S-217622 is approved, this drug will become the first domestically produced new crown oral drug in Japan.
It is worth mentioning that the introduction of this oral drug for the new crown in Japan has also pushed the stock prices of domestic companies such as Peking University Pharmaceuticals and Changjiang Health to the daily limit.
In the past two days, Peking University Pharmaceuticals and Changjiang Health have successively issued announcements of stock price changes in response to relevant rumors.
Peking University Medicine responds, publicThe company has never carried out the research and development of new crown special drugs, nor has it discussed cooperation with Japan’s Shionogi about 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 Shionoyi, on the “Luolit” luliconazole cream, which is responsible for product sales. At present, the two sides have not carried out cooperation on new coronavirus treatment drugs.
Multiple pharmaceutical companies enter the bureau
As of March 16, the cumulative number of confirmed cases of the new coronavirus worldwide exceeded 460 million, and the cumulative death toll exceeded 6 million. This is the deadliest pandemic that humanity has encountered in the past 100 years.
While the global investment in research and development has increased, the speed of the new coronavirus mutation has not slowed down, and even accelerated the mutation in the spread, from alpha, beta, gamma, delta, to now spreading Omicron of the world.
Omicron includes 3 main lineages, BA.1, BA.2, and BA.3. A study in Japan showed that since January this year, BA.2 has increased in pedigree frequency and surpassed BA.1 in several countries including the Philippines, India, Denmark, Singapore, Austria and South Africa, making it more transmissible. The U.S. Centers for Disease Control and Prevention said on March 15, local time, that as of March 12, the BA.2 clade infection cases of the Omikron variant are expected to account for 23.1% of the existing cases of new coronavirus variant strains 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 the 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 received emergency use authorization from the U.S. Food and Drug Administration (FDA) for a combination of nematevir (3CL protease inhibitor) and low-dose A two-part compound preparation of ritonavir. On January 20 this year, Merck’s new crown oral drug molnupiravir was allowed to be produced by 27 generic drug companies and supplied to 105 low- and middle-income countries.
On February 11 this year, the State Food and Drug Administration approved Paxlovid with conditions for the treatment of patients with mild to moderate novel coronavirus pneumonia that may develop into severe disease. Essence Securities analyst Ma Shuai believes that this approval shows that domestic regulators attach great importance to oral drugs for the new crown, and the development of domestic oral drugs for the new crown is expected to accelerate.
In fact, many domestic pharmaceutical companies have deployed a variety of oral anti-new crown drugs.
According to the research report of Huachuang, the “Azvudine (oral)” of real biology is in the clinical phase III; Oral)” has started clinical phase II/III research; oral 3CL inhibitors of Ascletis, Simcere, Zhongsheng, Junshi 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 “New Coronary Virus Pneumonia Diagnosis and Treatment Plan (Trial Version 9)” (hereinafter referred to as the “Diagnosis and Treatment Plan”), and the antiviral treatment was carried out. further specification. The “Diagnosis and Treatment Plan” includes 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 (ambavirumab/Romandel) mitelizumab injection).
The latter is a new crown-specific injection drug developed locally in my country. Existing clinical studies have shown that this antibody combination drug can reduce hospitalization and mortality by 80%.
“It still depends on what degree of infection these new crown oral drugs are aimed at. If it is only asymptomatic or mild patients, the market value of such drugs is not large. Because for For non-severe patients, their physical condition will gradually improve over time without intervention of drug treatment.” Shi Lichen said that the influence of new crown oral drugs on the domestic market may be limited, and the focus of development is overseas markets.