Which product is the hottest product on the new crown track is expected to become a blockbuster?

The threshold of the "blockbuster" depends on the industry's crowning king

In our country, products with annual sales of more than 1 billion yuan can be regarded as the blockbuster of domestic drugs

After the new crown epidemic, vaccines + neutralizing antibodies + oral small molecules, "blockbusters" have appeared in foreign countries, and "super blockbusters" have also appeared in the field of vaccines and neutralizing antibodies in China

1.

The first foreign vaccine to run out of the circle was the mRNA vaccine.

Pfizer's mRNA new crown vaccine Comirnaty (BNT162b2) has revenue of US$12.

Modena's Q3 financial report showed that the third-quarter revenue was 5 billion US dollars (expected to be 6.

On November 11, the Chief Medical Officer (CMO) Paul Burton of Modena cited French statistics as saying that young men between the ages of 12 and 29 suffered from myocarditis after being vaccinated with Modena, which was 13.

Data from the Centers for Disease Control (CDC) of the United States shows that the incidence of mild and severe illness among people vaccinated with Modena is lower than those vaccinated with Pfizer or Johnson & Johnson: for every 100,000 people vaccinated with Modena Only 86 of the people had breakthrough infections, but Pfizer had 135

The adverse reaction of the vaccine is not only the mRNA new crown vaccine, the adenovirus (Ad) vaccine has been reduced from the leader to the accompaniment due to the adverse reaction

Despite serious adverse reactions, AstraZeneca’s new crown vaccine sold for 1.

As of September 16, a total of 5.

CanSino's adenovirus vector new crown vaccine has a revenue of 2.

In September 2021, there are currently 25 new coronavirus vaccines in China that have entered clinical trials, and 14 of them have been approved overseas for phase III clinical trials

2.

The first approved oral small molecule was Gilead’s remdesivir (GS-5734, trade name Veklury), which was the only antiviral drug approved by the FDA for the treatment of Covid-19 in October 2020.
For the treatment of severely ill patients hospitalized with the new coronavirus, it can be used in adults and children 12 years and older weighing at least 88 pounds
.
The FDA has subsequently approved Remdesivir Emergency Use Authorization (EUA), allowing children under 12 years of age who weigh 8 pounds to 88 pounds, or weigh at least 8 pounds, to use Remdesivir for the treatment of severely ill patients with new coronary disease
.

Although the efficacy of Radixivir is controversial, Gilead still makes a lot of money: According to Gilead’s annual report, the revenue of Radixivir in 2020 is approximately US$2.
8 billion, and Gilead’s Q3 Radixivir sales are Gilead therefore predicts that its annual sales in 2021 will be as high as US$4.
8 billion
.

On November 4, the British Medicines and Health Products Administration (MHRA) announced the approval of the oral antiviral drug Molnupiravir developed by Merck/Ridgeback for the treatment of COVID-19 for the treatment of mild to moderate COVID- 19 adult patients
.
After Monupivir's EUA application is approved, the U.
S.
government will purchase 1.
2 billion U.
S.
dollars, equivalent to 1.
7 million products, and the U.
S.
price is about 705 U.
S.
dollars per person, which is significantly lower than Remdesivir’s 2,340 U.
S.
dollars per person
.
Some analysts believe that Molnupiravir's sales this year will exceed 3 billion U.
S.
dollars, and next year's sales will be close to 7 billion U.
S.
dollars
.

The efficacy data of Pfizer Paxlovid (the main ingredient PF-07321332), which announced the Phase III clinical results in November, is even better.
Pfizer has applied for emergency use of paxlovid antiviral drugs in the United States this month
.
The disadvantage of Pfizer's PAXLOVID is that it needs to be used in combination with HIV drugs to take effect.
In the Phase II/III clinical trial initiated in July 2021, pf-07321332 will be administered with low-dose ritonavir
.
Ritonavir is an old drug widely used to treat HIV infection
.

On November 16, Kailaiying disclosed a major daily operation contract announcement
.
According to the announcement, the company's wholly-owned subsidiary Asymchem, Inc and Jilin Kailaiying Pharmaceutical Chemical Co.
, Ltd.
have signed a new batch of "supply contracts" for a small molecule chemical innovative drug CDMO service that has already been cooperated with a large American pharmaceutical company
.
As of the signing date of the contract, the cumulative contract value of CDMO services for this product is 480 million U.
S.
dollars (approximately 3.
1 billion yuan), and the contract period is 2021-2022
.
It is generally speculated in the industry that the cooperative company announced by Callyin is Pfizer, and the cooperative product should be the raw material of Pfizer's new crown oral drug Paxlovid
.

RNA polymerase inhibitor/protease inhibitor oral anti-coronavirus drugs.
Domestic companies are currently leading players such as Junshi Biology and Frontier Biology
.

On October 4th, Junshi Biotechnology and Wangshan Wangshui reached a cooperation to develop oral nucleoside anti-coronavirus small molecule drug VV116.
Currently, it has carried out phase I clinical trials at home and abroad
.
VV116 is an oral nucleoside anti-coronavirus candidate drug jointly developed by many domestic scientific research institutions including Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Wuhan Institute of Virology, Chinese Academy of Sciences, and Xinjiang Institute of Physics and Chemistry, Chinese Academy of Sciences
.
Preclinical pharmacodynamic studies have shown that VV116 has a significant inhibitory effect on the original virus strains and mutant strains of the new coronavirus, such as Delta virus, in vitro
.

Frontier Biosciences and Shanghai Institute of Materia Medica, Chinese Academy of Sciences, the new crown drug candidate FB2001 (DC series drug candidates) is a protease inhibitor, the same as Pfizer PF-07321332
.
FB2001 is currently conducting Phase I clinical trials in the United States
.

At present, there are three domestic products in phase III clinical trials, namely, Climycin from Shenyang Tonglian Group, Prokrulide from Kaifeng Pharmaceutical, and ASC09F/ritonavir from Golly Pharmaceuticals
.

The Phase III clinical trial of the androgen receptor (AR) antagonist "Prokalamide", which pioneers the pharmaceutical industry, is currently underway in the United States, South America (including Brazil), the European Union, Asia and other countries and regions, and will be launched in July 2021.
Obtained Paraguay’s first emergency use authorization (EUA) in October
.
Phase II data showed that the risk of severe death was reduced by 78%
.
According to the clinical trial of Prokrutamide in Brazil, this drug reduced the hospitalization rate of outpatients by 91%, but the preprint articles of the results of the clinical trial of Prokrutamide in Brazil have been submitted to NEJM and The Lancet, both It was rejected on the grounds that the data was "unbelievably good"
.

3.
Neutralizing antibodies: The 7 billion market will be squeezed to 2 billion by oral small molecules

2% of the world’s population may not respond well to the new crown vaccine due to various reasons (such as blood cancer patients receiving chemotherapy, patients receiving dialysis, multiple sclerosis or rheumatoid arthritis patients taking immunosuppressive drugs, etc.
) Injecting neutralizing antibodies may provide them with protection and provide a new option for controlling the epidemic
.

On October 14, 2021, Regeneron announced that the U.
S.
FDA has granted priority review qualification for the biological product license application (BLA) of its neutralizing antibody combination therapy REGEN-COV (casirivimab+imdevimab) for the treatment of ambulatory patients.
COVID-19 patients, and as a post-exposure prophylaxis therapy for high-risk groups
.
The press release pointed out that if approved, it will be the first new coronavirus neutralizing antibody officially approved by the US FDA for both the treatment of COVID-19 patients and as a post-exposure prophylaxis
.

There are currently three COVID-19 neutralizing antibody therapies approved by the FDA or used for the treatment of COVID-19 patients through emergency use authorization (EUA), namely Casirivimab and Imdevimab combination therapy (Regeneron), Bamlanivimab and Etesevimab combination therapy (Lilly/Jun) Real biological), Sotrovimab (GSK/Vir Biotechnology), and the anti-cytokine receptor antibody tocilizumab
.
It is estimated that in 2021, the regenerative medicine Casirivimab and Imdevimab combination therapy market will reach 5.
3 billion U.
S.
dollars, Bamlanivimab and Etesevimab will exceed 2 billion U.
S.
dollars, and Sotrovimab (GSK/Vir Biotechnology) market size will be around 200 million U.
S.
dollars
.

In terms of domestic research drugs, Junshi Bio-JS016, the national leader mentioned above, is the first new coronavirus neutralizing antibody therapy in China to enter clinical trials and the second in the world
.
Junshi Biology issued an announcement in November stating that its second clinical trial application for new crown neutralizing antibody JS026 injection was approved by the China Food and Drug Administration for the prevention and treatment of new coronavirus pneumonia (COVID-19)
.

The domestic pharmaceutical company Tengshengbo Pharmaceutical announced on October 9 that it has submitted its under-research SARS-CoV-2 combination therapy BRII-196/BRII-198 emergency use authorization (EUA) application to the US FDA, and its third phase has been unblinded and drug delivery The group achieved zero deaths after 28 days of treatment, and the control group had 8 deaths
.

On October 5, AstraZeneca’s AZD7442, a mixture of tixagevimab and cilgavimab, both were derived from B cells donated by patients who recovered from COVID-19
.
If authorized, this will be the first long-acting antibody cocktail therapy against COVID-19
.

Danxue Bio's new crown neutralizing antibody DXP-604 is undergoing phase II clinical trials in China and has been approved as a sympathetic emergency treatment in Beijing Ditan Hospital, mainly for mild and ordinary patients
.
As of November 2, 14 patients have been treated
.

The cost and price of neutralizing antibody drugs are high, with a dose of US$2,100, and intravenous injection is required, so their popularity is greatly restricted
.
Under the attack of oral small molecules, the overall market for neutralizing antibodies is expected to decline further.
In 2022, the global market is estimated to be only US$2 billion
.
At present, 20 neutralizing antibodies have been approved for clinical use in the world, and Chinese pharmaceutical companies have participated in nearly half of the research and development.
The neutralizing antibodies are mainly based on foreign markets.
Even if the follow-up products are listed abroad, there is no product market blessed by foreign marketing teams in the future.
Not optimistic
.

4.
Summary

Judging from the sales of domestic new crown drugs and the reaction of the secondary capital market, the new crown prevention method may not only produce a blockbuster of 1 billion yuan, but also bring a daily limit.
It is already a hot track, especially domestic For vaccines and neutralizing antibodies, the number of competing manufacturers has begun to smell of "surplus".
It is expected that small molecules will soon have a lot of long-term follow-ups.
Manufacturers who are only planning to enter the market now, if the R&D team cannot overtake or overtake a corner or It is too late for clinical research to be good enough to replace existing therapies
.