[Transfer] The first domestic new crown oral medication is unveiled: Will it become the end of the epidemic?

[Transfer] The first domestic new crown oral medication is unveiled: Will it become the end of the epidemic?

Source: amino observation/Zhu Lai

After a long wait, the first domestic new crown oral medication finally appeared.

On July 25, Azfdin, who had the conditions to approve the real creature, increased the application for the treatment of new coronary virus pneumonia indications.

The reason for "increase" is that Azf is scheduled to be approved to treat AIDS in 2021. With the expansion of the indications, Azf will also become the first new crown oral medicine in China to be approved to be listed.

In theory, oral medicine has no fear of mutation. No matter how the virus mutates the strike part, it still exists. Because of this, the market is looking forward to it.

However, because of less data disclosure, the controversy about Azfdin has been constantly, such as whether the clinical end point meets the CDE standard, whether the data disclosed is rigorous enough, and so on.

So, with the approval of listing, can the controversy and hope that can be a "new crown terminal"?

/ 01 /

The first domestic new crown oral medication from the transition

The reason why Azf's must be the first to hit the line is largely the victory of the "old medicine and new use" strategy.

In fact, as early as July 2021, Azf had been approved to be listed, but at that time, the adaptive disease was the treatment of AIDS. That's right, Azf was set at the beginning of the project, which was a drug that was anti -AIDS.

So why can Azf be related to the new crown? The answer is, temporary rescue field because of coincidence.

As a RNA virus, the new coronary virus requires the use of nucleoside and nucleotide for RNA synthesis. Therefore, a nucleoside -based antiviral drugs widely used in clinical practice may have the potential to treat new crown infections.

It happens that Azf is a member of the nucleoside (acid) inverting enzyme inhibitor and is a nucleoside -based dual -targeted drug. Because the target target is the same, in principle, it is not wrong to use it to treat the new crown.

It is in this context that the R & D team of Azf believes that the product may also be used for new crown therapy, and even patients with mutant strain infections.

The research officially kicked off, and the initial results also quickly landed. In October 2020, a paper published in Nature "Azvudine (FNC): A Promision Clinical Candidate for Covid-19 Treatment" has initially confirmed that Azf's potential effect has the potential effect of treating new crowns.

According to this study, Azfdin has significant help for the infected person to turn overcast time. Among them, the average duration of the nuclear acid to the Azfdin Treatment Group is 2.6 days, and the control group is 5.6 days.

Of course, although the principle of treatment is established and preliminary data proves, Azf is still effective based on hypothesis for the effectiveness of the new coronal virus.

In terms of specific mechanisms, the above research only indicates that Azf may be embedded and inhibited related polymerase in the process of RNA synthesis of the new crown virus, which eventually leads to RNA copying and termination. And, this is only based on smaller clinical samples and is not rigorous.

Regardless of the mechanism, to prove that Azf has the effect of treating a new crown, it must be proved by clinical trials with a larger sample amount.

In April 2020, the third phase of Azfding's new crown was approved by CDE. The approval of the treatment of new coronary virus pneumonia is also based on this clinical trial result.

However, the result has not yet been fully disclosed. Because of this, the dispute and hope have been around Azfdin.

/ 02 /

Controversy and hope coexist

For a drug, the core is the treatment effect. Faced with the continuous invasion of the new crown virus, people have high hopes for domestic new crown oral medicines.

So, what exactly is the effect of Azfding for the new crown? At present, only a small part of the data can be referred to.

On July 16, the real creature released the results of the clinical trial of the Azfdin III:

(1) Significant improvement of clinical symptoms: Azf's fixed tablet can significantly shorten the moderate new type of coronary virus infection with pneumonia patients, improve the proportion of patients with improvement of clinical symptoms, and achieve clinical excellent results. On the first 7th day of the administration, the proportion of the subjects of the clinical symptoms improved 40.43%, and the placebo group was 10.87%(P value <0.001). There are very significant statistical differences with the placebo group (P value <0.001). (PPS set)

(2) Inhibit the role of new coronal virus: Azf will definitely have the activity of inhibiting the new coronary virus, and the virus clearance time is about 5 days.

(3) In terms of safety: The overall tolerance of Azf's fixed decision is good, and the incidence of adverse events has no statistical differences with the placebo group, and the risk of the subject does not increase.

It seems that the efficacy and safety of Azfdin are controversial? The core is the transparency of data.

First of all, the main clinical end of the product is to improve clinical symptoms. According to its information registered on the US clinical data platform, the standard is "the ratio of participants who reduce at least one clinical progress."

The dispute is that this is not the standard standard for the CDE.

In February of this year, the "New Coronatte Virus Pneumonic Anti -Virus New Pharmaceutical New Test Technology Guidance Principles (Trial)" issued by CDE (hereinafter referred to as "Principles") clarified clinical design standards. For mild or ordinary patients, the main endpoint is the priority "indicator to reduce intensiveness and mortality." This is also the main end of the study of Merck and Pfizer's oral medication;

The second main end point for retreat is to "promote the effectiveness and safety of clinical recovery", but the standard for clinical recovery is required.

For patients with severe or critical types, the main evaluation of "reducing the effectiveness and safety of critical complications such as death and respiratory failure."

In other words, according to the requirements of the CDE, reducing severe illness and mortality is the core indicator. The clinical improvement selected by Azf's selection, although it is also helpful to reduce intensiveness and mortality, it is not completely equal. Relatively speaking, the latter is more loose.

In many endpoints, Azf also sets indicators to reduce intensive rates and mortality, and has not yet announced clinical data.

In addition to the ending of the data, another controversial point about Azf is the data set. As mentioned above, phase III clinical data is based on PPS set.

Under normal circumstances, clinical data is mainly divided into ITT analysis sets (intention analysis sets), FAS set (full analysis set), and PPS sets (conforming to solution sets).

To put it simply, the number of analysis of these three levels from large to small sorting is ITT, FAS set, and PPS set. As shown in the figure below, the relationship is included.

The less the crowd involved, it means that the conditions are more accurate and more likely to draw better conclusions. If the proportion of subjects that are eliminated by the scheme set will affect the effectiveness of the entire test results.

Because of this, according to clinical requirements, due to the difficulty of ITT set analysis, the FAS and PPS sets need to be used for statistical analysis. When the data of the two is consistent, the credibility of the test results can be enhanced; when the inconsistency is inconsistent, the differences need to be discussed and explained.

Therefore, Azf's only announced data of the PPS set this time also made the market controversy.

Of course, the specific application data must have submitted the CDE review. CDE's approval of Azfdin's listing must also be based on sufficient data. This is also the hope of the first domestic new crown oral medication.

/ 03 /

Future: the efficacy and safety fight

Azf was approved to be listed. The first domestic new crown oral medicine came out. This is a good thing for pharmaceutical companies, people and even countries. Of course, in addition to joy, we must return to the real business world.

In the long run, the core of the competition for the new crown oral medication depends on two factors: efficacy and safety.

In this regard, overseas markets have proven.

As the world's first approved small molecule oral medication, Molnupiravir of Murishadon was indeed sold out of sales at the beginning of its listing. The Merid East quarterly reported that Molnupiravir's revenue in the first quarter was 3.2 billion US dollars, which was more than twice the sales of PaxLovid.

Earlier, Molshadon's expected Molnupiravir revenue for annual revenue was 50 to 5.5 billion U.S. dollars. Today's sales revenue in just the first quarter has reached 64%of the annual expectations.

However, things are reversing. PhaxLovid's sales since May are surging, while Molnupiravir's sales have begun to decline. There is no reason for him, molnupiravir is not as effective as Paxlovid.

Back in China, there are many domestic new crown oral medications. Including the Sim0417 of Xianyou Pharmaceutical, the VV116 of the Junshi Bio / Wangshan Wangshui, the Puklunamide of the Pharmaceutical Pharmaceutical, the SHEN26 of the Koxing Pharmaceutical, and the Ray1216 of all beings, involved 3CL protease, RNA aggregation A variety of technical routes such as enzymes.

After Azfdin, there were only one step away from some new crown oral medication.

In comprehensive consideration of the current situation of the epidemic prevention and control, our requirements for the new crown oral medication have long been not only solved the problem that there is nothing, but the amount and quality. In other words, what we really need is actually high -efficiency, safe and suitable products.

The battle for the domestic new crown oral medication has already launched. In the future, who can meet the curative effect and economic value will undoubtedly be the ultimate king.

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