The most "hot" new crown oral drug Azvudine: the data has not yet been unblinded, and the second level has already been hyped

At the end of March, the new crown oral drug azvudine, which was reported on the Internet, was about to usher in the third phase of data unblinding, but there was no relevant update on the entire social media and all information disclosure platforms

As a sector in the secondary market that most attracts investors' nerves, any news update on the new crown oral drug is behind a heavy game between the long side and the short side

However, Shenlanguan has learned from various channels that the progress of "Azvudine data unblinding" is still unclear.

Not long ago, the communication meeting of the real biological application posted on the official website of the Food and Drug Administration was just a very ordinary communication

As early as February this year, CDE issued clinical guidelines for new crown drugs, the purpose of which is obvious, to speed up the approval efficiency of new crown oral drugs

According to the statistics of Huachuang Pharmaceutical, as of now, there are 11 new crown oral drug projects in progress in China, and three in total in the third phase, namely Junshi's VV116, Kintor Pharmaceutical's Prokalutamide, and Real Biological of Azvudine

As one of the fastest clinical projects, what is the clinical situation of Azvudine, and what kind of company is the real biology behind it?

-01-

Azvudine listing progress bar is slow

According to the news on the Internet on April 13, although the results of unblinding have not yet come out, it is true that "the policy layer attaches great importance to it"

A relevant person mentioned to Shenlanguan: "The Chinese Food and Drug Administration and other departments are watching the clinical situation of various new crown drugs in China through the 'new crown emergency team'.

Therefore, based on this, there is no such thing as "the data is out, but it is deliberately hidden and not reported" in real creatures

It is reported that Real Life has plans to be listed on the Hong Kong Stock Exchange.

Compared with last year's new crown vaccine, as another major component of the "anti-epidemic toolkit", the approval of domestic new crown oral drugs is much slower.

Previously, the new crown oral drug targeted the hospitalization rate and severe improvement rate as the clinical endpoints, and it is difficult to make differentiated clinical data at present

In the "Clinical Guidelines for New Crown Drugs" released by CDE in February this year, in the design of clinical endpoints, the core focuses on the endpoints of symptom improvement such as "proportion of hospitalized or dead patients" and "recovery time"

During this time, many new crown oral drug research companies and experts have also been calling for "reducing viral load" as the primary clinical endpoint

"Because this is an infectious disease after all, the current core problem is to reduce human-to-human transmission

Previously, Shenlanguan also learned in the interview that "reducing viral load is very important in blocking community transmission, which is suitable for the current China's epidemic prevention and control ideas" (for details, see: "Why are domestic new crown oral drugs not approved?")

-02-

New use of old drugs: why are these two companies ahead?

Among the domestic new crown oral drug projects, the fastest ones are currently proclutamide and azvudine.
The common feature of these two drugs is "new use of old drugs"
.

Prolukamide itself is used as an AR inhibitor for the treatment of AR-positive prostate cancer patients, and it was developed into a new crown drug halfway
.

Prokalutamide, after the research trial in Brazil obtained very positive clinical trial data, the progress in the United States has experienced twists and turns
.
The "full population" was selected for the clinical trial scope of prokalutamide, which launched a phase III clinical trial in the United States in March last year
.

The "whole population" trial design has no restrictions on underlying diseases and unvaccinated, which greatly increases the difficulty of making significant differences between the treatment group and the control group
.
At the end of December 2021, the interim results of the Phase III clinical trial of prokamide in the treatment of mild to moderate non-hospitalized patients with COVID-19: did not reach statistical significance
.
But then, Kintor did not adjust the plan and continued the Phase III clinical trial in the United States
.

On April 6, 2022, Prokluamide disclosed the key data of the Phase III trial in the United States.
In terms of the existing efficacy data, the results look more optimistic
.
However, some people in the industry believe that the unblinding data of proclutamide (not all of which have been released) are more like the results of re-analysis of the data after unblinding, picking out subgroups that may have statistical significance
.

However, with the situation of "mostly asymptomatic infections or mild patients" caused by the Omicron strain, the EUA review rules of the US FDA are also "loosening": On February 11, 2022, the US FDA announced Approved the emergency use authorization (EUA) of Eli Lilly's new crown neutralizing antibody Bebtelovimab.
Although Bebtelovimab designed the time for "symptom remission" based on the standard of the Phase III clinical endpoint, when it finally passed the review, it did not meet the "statistical" In the case of “significant differences”, it should actually be that the FDA lowered the original standard and passed the review
.

Under this circumstance, the review environment faced by Prokluamide is much more relaxed
.
It is reported that Kintor is preparing a CSR report and plans to submit an EUA declaration to China (conditional approval), the United States and other healthcare authorities as soon as possible
.

Azvudine, as a nucleoside reverse transcriptase inhibitor, was first used for AIDS indications
.
In fact, as early as last July, Azvudine, as a new treatment for adult HIV-1 patients with high viral load, obtained conditional marketing approval from the State Food and Drug Administration, and is currently developing hepatitis B and tumor indications
.

The global multi-center clinical trial of Azvudine on COVID-19 infection was launched in February 2020.
The evaluation of safety and drug absorption has been basically done before, and there are ready-made preclinical data for a newly opened indication, which makes Azivudine It will be possible to start directly from Phase I/II, eliminating many preclinical steps
.

In August last year, Real Bio completed a $100 million Series B financing, led by the old shareholder Yifeng Capital and the new Yingke Capital.
After that, Real Bio directly accelerated the clinical application of its new crown indications for azvudine.

.

The developer of Azvudine is Chang Junbiao, the vice president of Zhengzhou University in Henan and a professor of the Department of Chemistry (now the vice president of Henan Normal University).
In 2011, Chang Junbiao was converted from the laboratory of Zhengzhou University with 40 million yuan The Zivudine (FNC) project found Wang Chaoyang, a private entrepreneur in Henan, and landed together, and there was a later real creature
.

In the past few years, there was basically no sound in Real Creature.
The project was advanced little by little with the funds of the big boss.
A major turning point was the addition of Du Jinfa in 2015
.

Du Jinfa was a senior scientist of Gilead before, and his greatest achievement was to lead the development of Sofosbuvir (Sovaldi), the hepatitis C drug product that Gilead made its fortune, which basically accomplished Gilead's transformation from a biotech to a TOP10 pharmaceutical company
.

With such a bright background blessed by star projects, Du Jinfa's career path is not difficult to follow
.
Shenlanguan learned that because Du Jinfa and Chang Junbiao both had study experience in the Institute of Pharmacy, Chinese Academy of Sciences, this "brotherhood" relationship led Du to come to Pingdingshan, Henan (where the company is located), as the company's CEO and CSO
.

Since then, Real Bio has successively recruited Dr.
Dang Qun, who was the chief scientist of Merck in the United States and later served as the vice president of CSPC Group, as well as Guo Changyue, who is in charge of medicine, and Wang Xiang, who is in charge of drug optimization.
world experience
.

The team configuration with this background is already a mid-to-high-level biotech bureau, but there was no first-level funding in the early stage, and the first round of Yifeng is already in 2020; secondly, the headquarters is located in Henan, and the biopharmaceuticals such as Sushen and Sushen are located in the north.
Star Industrial Park has nothing to do with it.
Except for the local government, there is basically no blessing from geographical effects.
Therefore, real creatures are rarely exposed before the new crown small molecules become popular this time
.

This time, the popularity of the new crown drug has given a qualitative improvement to its B round financing valuation
.

-03-

The end of the new crown oral drug

Just looking at the domestic market, in the context of a population of 1.
4 billion, the imported Pfizer P drugs cost 2,300 yuan per box, and the production capacity is limited, so it is difficult to put them into large-scale use as domestic standing drugs, and the anti-epidemic toolkit needs to be improved urgently.
It is only a matter of time before the drug is approved
.

But what about after approval?

According to a meeting minutes of Real Biology, the marketed azvudine as an AIDS drug is priced at 25.
86 yuan/mg (tablet).
According to the dosage of 5mg/day, the daily expenditure is more than 100 yuan, and the price of each bottle is also About 900 yuan or so
.

Judging from the comparison of the mature drug market with large clinical demand at present, the new crown oral drug, a product with "large dosage and urgent demand", is likely to be dominated by medical insurance and government-guided prices
.

But that doesn't mean real creatures aren't profitable
.
Under the national scale, no matter how low the net interest rate is, the final sum is not a small amount
.
Moreover, nationwide procurement can solve the channel problem of real organisms - the company does not need to build commercial channels from 0 to 1, which is a considerable cost for a start-up company
.

It is worth mentioning that although the price of azvudine API is not low at present, there is limited room for price reduction
.
However, if Azvudine is really approved and put into use on a large scale, there is a high probability that the government will also intervene in the price of upstream raw materials.
Under the effect of scale, as a drug developer, it will not be caused by the combination of terminal price reduction and high cost.
The profit margin of this segment is lower, and this incremental increase will definitely play a key role in promoting the company's development
.

The new crown epidemic has brought great turmoil to the society, but it is also a historic development node for some related industry chain companies
.
Due to the public health nature of the new crown epidemic, the new crown oral drug will also be a product with "strong policy influence"
.

Especially under the "breaking defense" of Omicron, China's new crown epidemic broke out on a large scale in Jilin, Shanghai and other places, especially in Shanghai, the cumulative number of infected people has reached 300,000 (as of April 15)
.
Under the huge infection base, oral drugs for the new crown will become a large and indispensable segment of the market besides vaccines
.