Different players in the tens of billions market enter two domestic pharmaceutical companies to enter Phase 3 clinical trials

A few days ago, the US FDA has expanded the emergency use authorization (EUA) of the new crown neutralizing antibody cocktail double antibody therapy (estivirimab and banivirimab) to include post-exposure prophylaxis (PEP) for specific populations New crown prevention, including those at high risk who are 12 years and older who have not been fully vaccinated against COVID-19 or who may not be able to develop an adequate immune response after being fully vaccinated, as well as those who have been in contact with people infected with the new crown or exposed in institutional settings (including nursing homes and prisons) People at higher risk

Junshi/Lilly's double antibody therapy has experienced ups and downs

Was called out for ineffective against mutant strains

Estevezumab (JS016) is a recombinant, fully human anti-SARS-CoV-12 monoclonal neutralizing antibody for the treatment and prevention of COVID-19

In June 2020, JS016, as the world's first new coronavirus neutralizing antibody to be tested in healthy volunteers, entered clinical trials in China and the United States

In November 2020, Eli Lilly submitted an emergency use authorization application to the FDA for the treatment of esvirizumab and banivirimab double antibodies for patients at high risk of mild to moderate new coronavirus pneumonia

In January 2021, Junshi Bio announced that the double antibody treatment of esvirizumab 2800 mg and banivirimab 2800 mg significantly reduced COVID-19-related hospitalizations and deaths in patients diagnosed with COVID-19 at a high risk of severe disease Event

In February 2021, diabody therapy received emergency use authorization in the United States and Italy for the treatment of patients with mild or severe COVID-19 who are at risk of progressing to severe COVID-19 and/or hospitalization

On June 25, there were media reports that the U.

On June 28, Junshi Bio made an emergency clarification announcement stating that the suspension of the supply of diabody therapy by the US government was not withdrawing its emergency use authorization in the United States

On August 27, the FDA and the Office of the Assistant Secretary for Emergency Preparedness and Response (ASPR) resumed the distribution of diabody therapy in some areas with low prevalence of resistant mutants; on September 2, the diabody therapy was resumed.

On September 15, the U.

On September 16, Junshi/Lilly's new crown neutralizing antibody cocktail diabody therapy emergency use authorization scope was expanded, adding post-exposure prevention (PEP) for specific populations

It is worth noting that on June 28, due to the news that the supply of diabody therapy was suspended in the United States, Junshi Biotechnology Innovation Board and the Hong Kong stock price were both hit

It is reported that the reason for the suspension of the supply of the dual antibody therapy in the United States is that the Centers for Disease Control and Prevention (CDC) has detected the P.

However, fortunately, considering that the double antibody therapy has been shown to maintain neutralizing activity against Delta and other mutants in the pseudovirus and true virus trials, and since June, the Delta mutant (B.

The neutralizing effect of esvirizumab on different mutant strains

Source: Shenwan Hongyuan Research Institute

Up to now, esvirizumab and banivirimab double antibody therapy have been authorized for emergency use in more than 12 countries and regions around the world, covering four continents: Europe, America, Asia, and Africa

Outstanding performance in the market

Entrants "flooded in"

At present, the FDA has approved (including EUA) therapies marketed for the treatment of new coronary pneumonia has reached 11 types

The status of new coronary pneumonia drugs currently approved by the US FDA (including EUA)

Source: Shenwan Hongyuan Research Institute

The rest of the available drugs are the same as Junshi/Lilly’s diabody therapy, and only have emergency use authorization.
Among them, the new crown neutralizing antibody drugs specifically include: Regeneron/Roche’s REGN-COV2 (casirivimab+ imdevimab) and Vir/GSK’s Sotrovimab
.
Among them, except for GSK's sotrovimab, a cocktail therapy consisting of two kinds of antibodies is used, mainly to deal with the risk of drug resistance of mutant strains
.

Granted EUA by the FDA for neutralizing antibody drugs for new coronary pneumonia

Source: Shenwan Hongyuan Research Institute

According to financial reports released by various companies, Eli Lilly’s new crown virus neutralizing antibody revenue reached 959 million U.
S.
dollars in the first half of the year, accounting for 7.
08% of total revenue (13.
546 billion U.
S.
dollars); Regeneron’s revenue in the second quarter of this year was 5.
14 billion U.
S.
dollars, from Xinguanzhong And antibody REGEN-COV revenue was 2.
76 billion US dollars, accounting for more than 50%; Vir/GSK's Sotrovimab was awarded the EUA by the FDA in May this year, and there is currently no sales data disclosed
.

Through the financial report data, it is not difficult to find that the market size of the new crown "special effect medicine" spawned by the epidemic has huge potential
.
According to the analysis of the Industrial Securities analysis report, by the end of 2020, the commercialization market space of neutralizing antibodies is expected to be approximately US$1.
83 billion to US$3.
44 billion.
At the end of 2021, the market space of neutralizing antibodies is expected to reach US$6.
87 billion to US$14.
64 billion
.
Among them, developed countries in Europe and the United States have a larger market space, reaching 5.
43 billion to 11.
04 billion U.
S.
dollars; the market size of developing countries is about 1.
44 billion to 3.
6 billion U.
S.
dollars
.

Facing the huge market temptation, large and small domestic and foreign pharmaceutical companies have entered the new crown neutralizing antibody
.
According to the Antibody Therapeutics database, as of September 2020, there are 98 neutralizing antibody projects targeting the S protein of the new coronavirus worldwide
.
Among them, 20 neutralizing antibody drugs have been approved for clinical use
.

AstraZeneca AZD7442-the world's first long-acting new crown neutralizing antibody cocktail therapy

AZD7442 is composed of two monoclonal antibodies from convalescent patients infected with SARS-CoV-2.
It prevents the virus from entering human cells by targeting the RBD binding domain of the viral spike protein
.
Vanderbilt University Medical Center was authorized to AstraZeneca in June 2020 and is currently conducting 3 global multicenter phase III clinical trials
.
On August 20, 2021, AstraZeneca announced that AZD7442 is effective for pre-exposure prevention of COVID-19 in adults, and it has initiated the relevant EUA application
.

Novartis DARPin Protein Therapy——"Cocktail in Molecule", Single Drug Targets Multiple Sites

In October 2020, Novartis and Molecular Partners reached a cooperation to jointly develop two DARPin protein therapies against COVID-19
.
The therapy provides a differentiated method for the treatment of COVID-19 through the "cocktail in the molecule" mechanism: it combines with 3 parts of the SARS-CoV-2 virus at the same time, neutralizes the virus through multiple mechanisms, and reduces The possibility of viral resistance
.
At present, two phase III clinical trials of this therapy are in progress
.

.
.
.

According to incomplete statistics, there are at least 10 drugs currently under study in China for the treatment of COVID-19 neutralizing antibodies
.
In addition to the JS016 jointly developed by Junshi Biology and the Institute of Microbiology, Chinese Academy of Sciences
.
Two other companies have entered Phase III clinical trials, including Prokrulide, a pioneering pharmaceutical company, and Tengshengbo, two neutralizing antibodies BRII-196 and BRIII-198
.
In addition, Maiwei Biologics' MW33, Shenzhou Cell's SCTA01, Luye Pharma's LY-CovMab, Fuhong Henlius HLX70, Jiminxinxin JMB2002, etc.
have entered the clinical trial stage
.

Pioneering the pharmaceutical industry Prokalutamide - Obtained the world's first EUA authorization for inpatients in Paraguay

Prokramide inhibits the function of the androgen receptor and down-regulates the expression of ACE2 and TMPRSS2 from the transcription level, thereby blocking the entry of SARS-CoV-2 into host cells
.
In May 2021, it was approved to carry out phase III clinical trials for outpatients and inpatients in the United States
.
It is expected that in Q4 of 2021, phase III clinical trials in the United States for mild to moderate outpatients with covid-19 will be completed
.
On July 16, 2021, the Paraguayan Ministry of Public Health and Social Welfare (MSPBS) formally granted an emergency use authorization of Prokruline for the treatment of COVID-19 inpatients in the MSPBS hospital system
.

Tengshengbo drug BRII-196/BRII-198-U.
S.
Phase III clinical interim data show good results

BRII-196/BRII-198 is a highly effective neutralizing antibody isolated from the serum of patients with COVID-19 convalescence by Tsinghua University and Shenzhen Third People’s Hospital during the progress of the epidemic in China in early 2020.
The two antibodies did not bind to RBD.
The two competing targets were modified by Fc at the same time to extend the half-life from 21 days to up to 3 months
.
The current Phase I and Phase II clinical trial data show that BRII-196/BRII-198 has good safety and tolerability
.
On August 25, the company announced the interim analysis data of the ACTIV-2 trial.
Among 837 outpatients with new coronary pneumonia at high risk of disease progression, compared with placebo, the composite endpoint of hospitalization and death was reduced by 78%, which was statistically significant.
Sex
.
It is expected that the EUA listing application will be submitted in the fourth quarter of this year
.

.
.
.

At present, the global epidemic cannot dissipate in a short period of time, and the demand for new crown "specific drugs" will not be immediately reduced in the future, and there must be a place for neutralizing antibodies
.

Reference source: Shenwan Hongyuan Research Report