China's Domestic COVID-19 Oral Antivirals Enter Final Approval Sprint: Junshi Biosciences, Genuine Biotech, and Others Advance Phase III Trials

Constant updates emerge from the race for specific COVID-19 therapeutics.

The latest news comes from Junshi Biosciences. At noon yesterday (March 16), Junshi announced that VV116, an oral nucleoside anti-SARS-CoV-2 drug co-developed with Suzhou Wangshan Wangshui Biopharmaceutical Co., Ltd., has initiated a Phase III clinical trial and completed the enrollment and dosing of the first patient.

That evening, Junshi Biosciences promptly released three sets of Phase I clinical data for VV116. The results demonstrated that VV116 exhibited satisfactory safety and tolerability in healthy subjects, with rapid oral absorption. Twice-daily repeated dosing at 200–600 mg maintained effective antiviral concentrations. These findings support advancing VV116 into Phase II/III clinical trials.

This marks the first public release of Phase I clinical data for a domestically produced oral small-molecule anti-SARS-CoV-2 drug. Currently, two oral small-molecule anti-COVID-19 drugs have received Emergency Use Authorization (EUA) worldwide. As an independently developed oral COVID-19 therapeutic in China, every step of VV116’s clinical progress has attracted significant attention.

China is grappling with its most severe wave of domestic COVID-19 outbreaks since the Wuhan epidemic, with scattered cases emerging across multiple regions. This trend has once again sparked discussions on the possibility of a “controlled relaxation” of pandemic prevention and control measures. As China’s epidemic prevention strategy gradually evolves, both vaccines and specific therapeutic drugs are indispensable. Therefore, this year, specific therapeutics are destined to become a highly watched industry sector alongside vaccines.

Which Chinese innovative pharmaceutical companies can seize the first-mover advantage?

Amid the current anti-epidemic landscape, as a strategic reserve on par with vaccines, there is significant attention on when Chinese innovative pharmaceutical companies will unveil their independently developed specific drugs for COVID-19, in addition to the monoclonal antibody combination therapy approved at the end of last year. The most optimistic predictions suggest that this milestone could be reached in the second half of this year.

More than a month ago, the National Medical Products Administration (NMPA) approved the import registration of Pfizer’s oral COVID-19 drug Paxlovid, marking the introduction of the first oral antiviral therapy for COVID-19 in China. Six days later, the Center for Drug Evaluation (CDE) issued the Technical Guidelines for Clinical Trials of Novel Antiviral Drugs for Coronavirus Disease 2019 (Trial Implementation), providing clear direction for domestic pharmaceutical companies seeking regulatory approval for their drug candidates.

At present, the most promising drugs likely to gain approval this year include Junshi Biosciences’ VV116. According to VCBeat New Medicine, under ideal circumstances, Junshi Biosciences will complete enrollment for its Phase III clinical trial in the second half of this year and then determine whether it is appropriate to submit a regulatory filing based on preliminary data. In addition, the progress of Kintor, Genuine Biotech, and Danxu Biopharma is also worth noting, as they have likewise entered Phase III clinical trials.

As an innovative pharmaceutical company that started with oncology drugs, Junshi Biosciences has experienced the unique challenges of developing COVID-19 therapeutics. In particular, the pandemic-induced changes in the availability of clinical patient resources have introduced uncertainties into drug development. In its public announcements, Junshi Biosciences stated that due to the long development cycles and multiple approval stages involved in pharmaceuticals, which are susceptible to various uncertain factors, there is a certain degree of uncertainty regarding the clinical trial progress, study results, and regulatory approval outcomes of VV116.

Junshi Biosciences began laying the groundwork for COVID-19 drug development in early 2020, just as the pandemic was breaking out. Given the high specificity of antibody development, the company initially focused on neutralizing antibodies. Among the four COVID-19 drug pipelines currently disclosed by Junshi Biosciences, two are antibody-based drugs and two are small-molecule drugs. However, since the second half of last year, Junshi’s resources have gradually shifted from neutralizing antibodies toward oral small-molecule drugs.

Currently, it appears that antibody drugs are more susceptible to immune escape by variant strains. The continuous mutation of SARS-CoV-2 has already rendered some antibody therapies ineffective.

DXP-593, a product of Danxu Biopharmaceutical, a leading domestic developer of SARS-CoV-2 neutralizing antibody drugs, is among the antibody therapeutics susceptible to immune escape. However, another Danxu product, DXP-604, has maintained potent activity against both the Delta and Omicron variants. Compared with oral small-molecule drugs, antibody therapeutics possess their own competitive advantages, particularly in combination regimens and cocktail therapies for COVID-19.

According to VCBeat New Medicine, Danxu Biopharmaceutical is currently actively preparing for the overseas Phase III clinical trials of DXP-604, while its domestic Phase II clinical trials are proceeding simultaneously. In March this year, Danxu Biopharmaceutical just completed a Series B financing round of nearly RMB 300 million.

The other two drugs that have entered Phase III clinical trials are Azvudine, an anti-HIV nucleoside dual-target drug developed by Genuine Biotech in Henan, and Proxalutamide, a next-generation androgen receptor (AR) antagonist independently developed by Kintor. The Phase III clinical trial of Azvudine for patients with moderate to severe COVID-19 has been completed in Brazil, while the Phase III clinical trial for mild cases is expected to be completed this July. The interim analysis of the U.S. Phase III trial of Proxalutamide failed to meet its primary endpoint, and the company plans to continue enrolling high-risk patients.

From late last year to early this year, multiple pharmaceutical companies—including Everest Medicines, Simcere Pharmaceutical, and Frontier Biotechnologies—entered the race for COVID-19 specific therapeutics, prompting the Center for Drug Evaluation (CDE) to issue technical guidelines for clinical trials. These guidelines aim not only to standardize clinical trial conduct but also to prevent the wasteful use of China’s already scarce clinical patient resources.

However, it is not difficult to observe that the companies currently making rapid progress and entering Phase III clinical trials are mostly innovative pharmaceutical enterprises that strategically positioned themselves in this therapeutic area early in the pandemic.

“SARS-CoV-2 is constantly mutating, leading to the obsolescence of some drugs and the emergence of new ones. However, the competitive landscape has remained largely unchanged, making it exceedingly difficult for latecomers to catch up,” an insider told VCBeat New Medicine. Facing viral mutations and uncertainties in global epidemic prevention strategies—both of which constitute the greatest challenges currently confronting the development of specific anti-COVID-19 therapeutics—companies often find themselves in a dilemma, with some choosing to abandon their efforts altogether.

Furthermore, several leading domestic companies and their collaborative R&D partners all have backgrounds in universities and research institutes. The development of COVID-19 therapeutics has particularly tested the close collaboration, efficient translation, and rapid advancement between enterprises and research institutions.

Among them, Junshi Biosciences’ VV116 was developed from an antiviral drug by the Shanghai Institute of Materia Medica, Chinese Academy of Sciences. In addition, Junshi’s collaborators include the Wuhan Institute of Virology, Chinese Academy of Sciences, and others.

Azvudine is a repurposed innovative anti-HIV drug, jointly developed by Professor Chang Junbiao’s team at Henan Normal University, Genuine Biotech Limited, and Beijing Union Pharmaceutical Factory.

Danxu Biopharmaceutical’s COVID-19 antibody drug was directly translated from a national-level key research and development project. After the outbreak of the COVID-19 pandemic, Professor Xie Xiaoliang’s team at Peking University employed high-throughput single-cell sequencing technology to analyze blood samples collected promptly from more than 60 convalescent patients at Youan Hospital, identifying multiple broadly neutralizing antibodies. Subsequently, Peking University licensed the relevant commercialization rights to Danxu Biopharmaceutical.

At its inception in August 2020, Danxu Biopharmaceutical entered into a collaboration with BeiGene. According to VCBeat New Medicine, the partnership has since been terminated. This year, Danxu Biopharmaceutical partnered with the Wuhan Institute of Biological Products, China National Biotec Group (CNBG), to advance the global Phase III clinical trials of its drug candidate.

Due to the small number of patients in China, with only sporadic cases reported, it is difficult to conduct large-scale clinical trials. Currently, although Beijing Danxu Biopharmaceutical Co., Ltd. has provided compassionate use treatment to over 400 patients domestically with positive feedback, this cannot serve as the basis for clinical trial applications.

Currently, most clinical trials of COVID-19 drugs conducted by Chinese pharmaceutical companies are being carried out in Belt and Road Initiative countries and South American nations. This involves communication with local public health authorities, as well as registration and regulatory bodies, and collaboration with international CROs. Therefore, prior drug development experience in these countries is crucial.

VCBeat News has learned that in the collaboration between Danxu Biopharma and China National Biotec Group’s Wuhan Institute of Biological Products, the latter will lead overseas clinical trials, leveraging its experience in COVID-19 vaccine development across Belt and Road Initiative countries.

The challenges currently faced by COVID-19 drug developers in conducting overseas clinical trials may well be the same issues that domestic biotech companies will encounter in their internationalization efforts.

It can be said that, amid viral mutations and uncertainties in global pandemic prevention policies, the development of COVID-19 therapeutics is not merely a race for speed, but a comprehensive “stress test” of the overall capabilities in new drug development:

From source innovation in basic research, to the conduct of overseas clinical trials and communication with local health and regulatory authorities, and finally to comprehensive control over the global epidemic situation and domestic prevention policies—who will be the first company to cross the finish line in this final sprint? The suspense is significant, making it highly anticipated.