On January 22, the National Health Commission and the State Administration of Traditional Chinese Medicine jointly issued the "Influenza Diagnosis and Treatment Plan (2025 Edition)" (hereinafter referred to as the "New Edition"). Compared with the "Influenza Diagnosis and Treatment Plan (2020 Edition)" (hereinafter referred to as the "2020 Edition"), the new version includes two anti-influenza virus drugs, Mabaloxavir and Favipiravir.

Amantadine and rimantadine were eliminated due to drug resistance issues. At the same time, the new version of the plan clearly stated that it is not recommended to use antiviral drugs with the same mechanism of action in combination. Many pharmacists pointed out to the 21st Century Business Herald reporter that this move is aimed at optimizing the treatment effect and reducing unnecessary side effects.

After the replacement of drugs, more and more companies have seen the development potential of the anti-influenza drug market. Competition in the oseltamivir market has become increasingly fierce. Nearly 50 pharmaceutical companies have obtained production approval numbers for oseltamivir phosphate capsules, and the production of granules is no longer the exclusive territory of East Sunshine Pharmaceutical.

With the entry of the new generation of anti-influenza virus drugs, Mabaloxavir Tablets, into the domestic market, market competition has further intensified. At present, Mabaloxavir Tablets have been approved for marketing by three domestic pharmaceutical companies. With the upgrading of research and development, new anti-influenza virus drugs under development may become new competitors in the future market.

Drug replacement

The new version of the plan further improves the pathogenesis, pathology, clinical manifestations and complications of influenza in children and the elderly, adds clinical mild and moderate classification standards, and improves the severe and critical standards.

At the same time, the new version of the plan refines the principles of antiviral treatment and supportive treatment measures such as respiratory and circulatory treatment for severe cases, and adjusts and optimizes the TCM syndrome differentiation treatment of influenza.

In terms of drug treatment, the new version of the plan clearly points out that the drugs currently available in my country that are sensitive to influenza viruses mainly include three categories: neuraminidase inhibitors, RNA polymerase inhibitors, and hemagglutinin inhibitors. For example, oseltamivir, peramivir, zanamivir, mabaloxavir, favipiravir, and arbidol.

Among them, oseltamivir, as a classic antiviral drug, has the mechanism of effectively cutting off the connection between infected cells and other cells by inhibiting the activity of neuraminidase on the surface of the virus, thereby curbing the replication of the virus.

Although oseltamivir, peramivir, and zanamivir belong to the category of neuraminidase inhibitors, there are significant differences in their administration methods and dosages. For example, oseltamivir is usually taken orally, zanamivir is an inhaled powder spray, and peramivir needs to be administered intravenously.

Mabaloxavir and favipiravir are both RNA polymerase inhibitors. According to the new version of the plan, mabaloxavir tablets are suitable for children aged 5 years and above and adults, and its dry suspension is specifically for children aged 5 to 12 years. Favipiravir is mainly suitable for the treatment of new or re-emerging influenza in adults, but it is only considered for use when other anti-influenza virus drugs are ineffective or ineffective.

It is worth noting that the new version of the plan excludes two drugs, adamantane and rimantadine. In fact, the 2020 version of the plan has clearly pointed out that the M2 ion channel blockers adamantane and rimantadine are resistant to the influenza virus strains that were prevalent at the time and are not recommended for use.

Zhao Yang, director of the Department of Pharmacy of the Fifth Affiliated Hospital of Zhengzhou University, told the 21st Century Business Herald reporter that deleting the two drugs adamantane and rimantadine is more in line with clinical needs.

The new version of the plan also clearly states that it is not recommended to use antiviral drugs with the same mechanism of action in combination. Zhao Yang believes that this suggestion is based on the fact that combined use will not improve the treatment effect, but may increase the burden on patients.

In addition, in response to the recent online statement that "the resistance rate of influenza drugs is very high", Roche previously told the 21st Century Business Herald and other media that due to the characteristics of the influenza virus itself, clinical studies have found that whether oseltamivir or mabaloxavir is used for treatment, a certain proportion of influenza viruses may have gene site mutations, and only a small part of the mutations will cause the virus strain to decrease in sensitivity to drugs.

However, influenza virus mutations do not mean that the virus has developed drug resistance.

"According to the WHO definition, influenza virus resistance refers to the ability of influenza virus strains to develop insensitivity to or resistance to drugs; WHO has strict standards for the degree of decreased drug sensitivity. Judging the drug resistance of influenza virus strains requires long-term and continuous monitoring and research." Roche emphasized.

In Roche's view, the instructions for mabaloxavir drugs in various languages around the world describe the site mutation rate of influenza viruses after treatment with mabaloxavir, rather than the drug resistance rate. It is neither rigorous nor scientific to equate the virus site mutation rate with the drug resistance rate.

In addition, according to the China CDC Influenza Weekly Report, since April 1, 2024, 51 influenza strains have been found to have decreased sensitivity or resistance to neuraminidase inhibitors. Since the launch of mabaloxavir in 2021, no strains have been found to have decreased sensitivity or resistance to RNA polymerase inhibitors.

Many experts also said that irregular medication is one of the important factors leading to influenza drug resistance. For example, oseltamivir needs to be used for influenza treatment for a 5-day course of treatment. If the patient does not complete the entire course of treatment as prescribed by the doctor, or stops taking the medicine on his own due to symptom relief, or changes the medicine at will, the virus may not be completely eliminated from the body, thereby increasing the risk of drug resistance.

Competition escalates

The development potential of the anti-influenza drug market is being seen by companies. Citing Frost & Sullivan's analysis data, East Sunshine Pharmaceuticals said that the scale of China's anti-influenza drug market is expected to rebound and reach 11 billion yuan in 2026, and further increase to 11.6 billion yuan in 2030.

In the anti-influenza drug market, oseltamivir was once regarded as a star product. The PDB database shows that the anti-influenza drug category mainly includes four therapeutic drugs including oseltamivir, and the total sales of these four drugs in the domestic pharmaceutical terminal market reached 11.405 billion yuan. Among them, oseltamivir occupies 86.48% of the market share with its excellent efficacy and wide market recognition.

At present, East Sunshine Pharmaceuticals still holds nearly half of the market share of China's anti-influenza drug market. According to the prospectus of Guangdong East Sunshine Pharmaceutical Co., Ltd. (hereinafter referred to as "East Sunshine Pharmaceutical"), in 2023, its main best-selling product for the treatment of influenza, Kewei® (oseltamivir phosphate), ranked first in the Chinese oseltamivir phosphate market, with a market share of 64.8%, accounting for 50.5% of the Chinese anti-influenza drug market in terms of sales revenue in 2023.

Oseltamivir has also become the performance pillar of East Sunshine Pharmaceutical. The prospectus shows that most of East Sunshine Pharmaceutical's revenue comes from the sales of Kewei (oseltamivir phosphate), with sales accounting for 52.4%, 81.2%, 86.9% and 74.9% of the revenue in 2021, 2022, 2023 and the six months ending June 30, 2024, respectively.

Oseltamivir sales increased significantly, and East Sunshine Pharmaceutical also made a profit.

According to the prospectus data, from 2021 to 2023 and the first six months of 2024, the operating income of East Sunshine Pharmaceutical was 1.058 billion yuan, 3.814 billion yuan, 6.386 billion yuan and 2.582 billion yuan, respectively, and the corresponding net profits were -2.046 billion yuan, -1.416 billion yuan, 1.014 billion yuan and 473 million yuan, respectively, and the adjusted net profits were -1.489 billion yuan, -384 million yuan, 1.227 billion yuan and 618 million yuan, respectively.

However, one reality is that competition in the oseltamivir market has become increasingly fierce. A reporter from 21st Century Business Herald checked the data of the State Food and Drug Administration and found that nearly 50 pharmaceutical companies have obtained domestic production approval numbers for oseltamivir phosphate capsules. Oseltamivir phosphate granules are no longer the exclusive product of East Sunshine Pharmaceutical. Shimei Pharmaceutical, Chengdu No. 1 Pharmaceutical Co., Ltd., Borri Pharmaceutical (Suzhou) Co., Ltd., Huayi Pharmaceutical Technology (Anhui) Co., Ltd., etc. already have production approvals. Oseltamivir phosphate dry suspension is approved for production by Shijiazhuang Siyao, Qilu Pharmaceutical, Chengdu Beite Pharmaceutical, etc.

With wolves in front and tigers behind, the new generation of anti-influenza virus drug Mabaloxavir Tablets has also entered the domestic market. In 2018, Roche's anti-influenza drug Mabaloxavir was approved for marketing by the FDA for the first time. In April 2021, Mabaloxavir was approved for marketing by the National Medical Products Administration, further intensifying the competition in the domestic anti-influenza drug market.

So far, three pharmaceutical companies in China have been approved for marketing of Mabaloxavir Tablets, forming a "1 original research + 2 domestic" pattern. In October 2022, Shijiazhuang Pharmaceutical Group Ouyi Pharmaceutical was the first to obtain approval for the marketing of Mabaloxavir Tablets, becoming the first domestic generic. In January 2025, the Class 4 generic drug Mabaloxavir Tablets applied by Zhengzhou Taifeng Pharmaceutical has been approved, becoming the second domestic company.

Market competition has not stopped. With the upgrading of research and development, a number of companies may also face the challenge of developing anti-influenza virus drugs in the future.

Zhang Wenhong's team from Huashan Hospital Affiliated to Fudan University published the latest research in Clinical Microbiology and Infection. The study evaluated the effectiveness and safety of ZX-7101A as a new influenza virus cap-dependent endonuclease inhibitor in the treatment of simple adult influenza through a randomized double-blind placebo-controlled trial, and explored its drug resistance rate. ZX-7101A is a prodrug of mabaloxavir, and has the same mechanism of action as mabaloxavir. From this point of view, this drug may be expected to become another option for anti-influenza treatment in the future.

Dingdang Express Medicine data shows that in the high-incidence season of influenza, in addition to oseltamivir and mabaloxavir, the sales growth of respiratory-related Chinese patent medicines is also very significant, such as the sales of Xiaoqinglong Granules and Four Seasons Antiviral Mixture doubled, the growth rate of Xiaochaihu Granules exceeded 80%, and the growth rate of Yupingfeng Granules, Xiaoer Chiqiao Qingre Granules and Lanqin Oral Liquid reached 30%.

As demand grows and more players enter the market, the story of the anti-influenza drug market will continue to be told.

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