After all, it was cold medicine that carried it all

The list of various hoarding drugs is varied, treating fever, sore throat... Traditional Chinese medicine and Western medicine are in battle.

Reflected in the stock market, it is also a hot scene. The stock price of Yiling Pharmaceutical, a manufacturer of Lianhua Qingwen, has risen nearly 3 times in the past two months, and ibuprofen API manufacturers Xinhua Pharmaceutical and Hengdi Pharmaceutical have gained several price limits, and all kinds of cold medicine and proprietary Chinese medicine manufacturers have also collectively entered a state of "excitement".

But only, the previously hyped "new crown special medicine" is calm. This can't help but make people feel that the speed of the market "turning over" is too fast, two months ago it was "Britney", and now it is "Mrs. Cow".

Neutralizing antibodies have become chicken ribs?

The first "new crown specific drug" to be cold is a neutralizing antibody.

In China, the first approved domestic new crown neutralizing antibody therapy is the cocktail therapy ambavirumab + romisivimab developed by Tengsheng Bo Pharmaceutical, Tsinghua University and Shenzhen Third People's Hospital, which was approved by the State Food and Drug Administration in December 2021 and commercialized in China in July 2022.

According to the data of the pseudovirus study of independent laboratories, the IC90 of ambavirumab + romisivimab combination therapy against the Omicron BA.4/5 variant was 16.61 μg/ml, and according to pharmacokinetic data, the plasma concentration was still about 18 times that of IC90 at 1 week after injection. The US FDA believes that the plasma concentration of monoclonal antibodies can be maintained at 10 to 30 times that of neutralizing virus IC90 at 1 week, which is effective.

Clinical data from ambavirumab/romisivimab

Image source: Tengsheng Bo Pharmaceutical's official website

In addition, Tengsheng Bo Pharmaceutical has also modified the antibody drug, the half-life of the drug is longer, and one injection can maintain the effectiveness in the body for 7 months to 9 months, with continuous effectiveness.

In March 2022, the National Health Commission approved the combination therapy to be included in the Diagnosis and Treatment Plan for Novel Coronavirus Pneumonia (Trial Version 9). Since March this year, a number of provincial and municipal medical security bureaus have successively implemented the directive of the circular to include combination therapy in the payment scope of local medical insurance funds.

However, even if the combination therapy of ambavirumab + romisivimab has been included in the payment scope of medical insurance funds in some regions, its high pricing still does not have the universality of large-scale application. The combination is priced at about $1,500 to $2,000 per person in the United States, and is currently priced less in China than in the United States, but closer to 10,000 yuan.

The overpriced pricing also cast a shadow over the business prospects of the combination therapy, causing Tengsheng Bo Pharmaceutical's share price to fall sharply.

In fact, this is not the worst. Due to the transformation of the new crown disease, the mainstream strain has evolved from a highly virulent, relatively less contagious original strain type to a low-toxic, but highly contagious Omicron.

According to a paper published in Nature in March this year, 17 of the 19 new crown neutralizing antibody therapeutics tested by researchers have no effect.

According to incomplete statistics, the main new crown neutralizing antibody therapeutic drugs currently under development in China include DXP604 of Dansequence Biologics, which is in clinical phase II; JS016 and JS026 of Junshi Biologics are in phase II and phase I, respectively; SCTA01 of Shenzhou Cell, in clinical phase II/III; Jimin's JMB2022, Luye Pharmaceutical's LY-Cov MAB, Sinopharm Zhongsheng new crown-specific immunoglobulin, and Bio-Thera BAT2022 are all in clinical phase I.

Due to the limitations of inconvenient transportation and storage, high price and other factors, even if the clinical trial is successful, it may indeed encounter insurmountable problems in commercialization.

Therefore, the burden of large-scale promotion of new crown treatment drugs may still fall on small molecule drugs. So, how is the progress of domestic research and development of small molecule drugs for the treatment of the new crown?

Can small molecule drugs be faster?

Recently, the research and development progress of new crown small molecule therapeutics has accelerated significantly, and many domestic companies have successively obtained clinical trial approvals.

On November 30, Yuekang Pharmaceutical announced that it had recently obtained the approval notice of YKYY017 drug clinical trial approval from the State Food and Drug Administration. YKYY017 nebulized inhaler is the latest generation of broad-spectrum, highly effective coronavirus membrane fusion inhibitor developed by Yuekang Pharmaceutical and the Institute of Pathogenic Biology of the Chinese Academy of Medical Sciences.

On the same day, China Resources Shuanghe also issued an announcement that the State Food and Drug Administration has approved its product CX2101A to carry out clinical trials for the treatment of new coronavirus pneumonia. CX2101A is a small molecule compound acting on the new coronavirus RdRp (RNA-dependent RNA polymerase), which was introduced by CR Shuanghe from Ligand in the United States in May 2022.

On November 29, Ascletis announced that the State Food and Drug Administration (NMPA) has approved its new drug candidate protease (3CLpro) inhibitor ASC11 new drug clinical trial application. The goal of the Phase I clinical trial is to establish a safe and effective dose for the conduct of a pivotal Phase II/III clinical trial in COVID patients, with Phase I clinical trials expected to be completed within the first quarter of 2023.

The new crown small molecule therapeutics under development that have carried out clinical trials have also made a lot of progress.

On December 12, Ascletis announced that the new crown oral RdRp inhibitor ASC10 achieved positive phase I clinical results. The safety and tolerability of ASC10 at all doses, including 800 mg twice daily, was good in Chinese subjects, and safety data were similar between the ASC10 treatment group and the placebo treatment group.

On December 11, Guangshengtang announced that its phase I clinical trial of GST-HG171 tablets, an innovative drug such as oral small molecule broad-spectrum anti-novel coronavirus 3CL protease inhibitor, has completed all subject enrollment and clinical observation, and recently obtained a clinical research summary report. The results showed that GST-HG171 had good safety, tolerability and pharmacokinetic characteristics, and achieved the expected purpose of the test.

On November 24, Sinovac announced that its phase II clinical study protocol for the treatment of mild and common new coronary pneumonia patients with SHEN26 under development has been approved by the ethics committee. SHEN26 capsule is a broad-spectrum RNA-dependent RNA polymerase (RdRp) inhibitor with potent in vitro inhibitory activity against different novel coronavirus variants according to laboratory data.

According to incomplete statistics, the small molecule drugs for the treatment of new crown with rapid clinical trials in China, including Junshi Biologics' RdRp inhibitor VV116, Pioneer Pharmaceutical's proclomide, Zhongsheng Pharmaceutical's RAY1216, and Simcere Pharmaceutical's SIM0417 are already in clinical phase III in China;

The rest are in the relatively early stage of FB2001, Guangsheng Zhonglin/WuXi AppTec's 3CL protease inhibitor, and Zhongsheng Pharmaceutical's RAY003.

After all, it was cold medicine that carried it all?

In the past week, many netizens have shared some symptoms of infection with the new crown virus, according to data recently compiled by "Liberation Daily", ordinary symptoms account for more than 90%, the most frequent of which are cough, fever, sore throat.

Most patients think that infection with the new crown is similar to colds and severe colds, and symptoms such as cough, pharyngitis, fever, nasal congestion, and headache will occur.

In addition to common symptoms, the proportion of high-risk symptoms including dyspnea, chest pain, and persistent high fever was small, only 2.3%; The proportion of asymptomatic patients was 6.6%.

Academician Zhong Nanshan said in an exclusive interview with Xinhua News Agency on December 9 that from the perspective of the vast majority of patients in the world and China, they can recover about a week after being infected with Omicron, and the symptoms are generally the most severe on the 1st to 3rd days, and the nucleic acid test results on the fourth and fifth days often turn negative. In general, the vast majority of people diagnosed with the Omicron virus strain will recover within 7 to 10 days.

Therefore, the main products of most ordinary people's "hoarding medicine" are drugs that relieve cold symptoms, such as antipyretic drugs ibuprofen, acetaminophen, etc.

Among these products, proprietary Chinese medicines account for a large proportion. On December 7, the Comprehensive Group of the Joint Prevention and Control Mechanism of the State Council to Respond to the New Crown Pneumonia Epidemic issued the "Guidelines for Home Treatment of Persons with New Coronavirus Infection", and gave a reference table of commonly used drugs for home treatment, and a number of proprietary Chinese medicines were included in it.

epilogue

The long-term coexistence of the new crown virus and human beings may be a reality that has to be faced.

Although ibuprofen, acetaminophen and some proprietary Chinese medicines have helped relieve symptoms and shorten the course of the disease, the need for new crown treatment drugs is still necessary and urgent.