On August 3, many practitioners in the pharmaceutical industry discovered that the “Non-clinical and clinical non-clinical and clinical anti-viral drugs for new epidemic strains of novel coronavirus infection” published on the official website of the Center for Drug Evaluation on August 1 Evaluation Criteria Questions and Answers”, has been quietly taken down.
This has rarely been the case before. The Health Condition Bureau called the relevant business department of CDE, but it has not been connected. Some domestic companies engaged in the research and development of oral drugs for COVID-19 said it was unclear why this happened.
Although this document is called “Q&A”, it is actually a “referenced technical standard” provided by the State Food and Drug Administration for the development of new crown drugs, and it has been approved by the Food and Drug Administration. It will be released after review and approval, and it is clearly stated that “it will be implemented from the date of release”.
On August 2, the first domestically-produced oral drug for COVID-19, Azvudine, was officially put into production in Henan. The total designed output of the Pingdingshan production base in Henan is 3 billion tablets per year. However, there are still discussions in the industry about the basis for the approval of Azvudine.
Q&A alleviates industry anxiety at least to some extent. Previously, the CDE’s gold standard for approval of new crown drugs has always been to reduce severe disease and mortality. Some people in the industry believe that this standard is indeed a bit “strict” as the infectivity of the virus declines and the domestic epidemic control is in place. In the new regulations, the standard is “relaxed”, and the market sees it as a major benefit for domestically produced new crown oral drugs.
However, this “good” document was suddenly withdrawn, and new crown drug development and investment institutions have new doubts.
Modifying the primary endpoint does not mean releasing approval
Industry insiders told the Health Knowledge Bureau: “From the perspective of content, The expressions of the new standard are very objective and in line with the facts. As for why it was withdrawn, we also I can’t guess, maybe it’s just a technical reason.”
“Q&A” mentioned a total of 5 questions, of which the pharmaceutical industry is more concerned about the second and fourth questions, which correspond to nasal and pharyngeal sprays and light and ordinary The patient primary efficacy endpoint. What the market is most concerned about is the adjustment of clinical endpoints of new crown drugs.
In accordance with the pilot version of the “Technical Guidelines for Clinical Trials of New Antiviral Drugs for Novel Coronavirus Pneumonia” released by CDE in February this year, the primary endpoint of development of drugs for patients with mild or common symptoms is to alleviate severe disease and mortality. This is also the goal set by Pfizer and other multinational pharmaceutical companies for the new crown drug. “Clinical improvement” was only used as a secondary endpoint.
This time, the once “alternative” is the preferred option. According to the CDE, this is due to the low virulence of the Omicron variant, and patients “have a low rate of progression to severe/critical illness or death, making it difficult to observe improvements in clinical outcomes” strong>, so the improvement of clinical efficacy indicators was considered as the primary efficacy endpoint.
This tongue-in-cheek description is exactly what happened to Junshi Biotech VV116 before.
During the Jilin epidemic in March this year, asymptomatic and mild cases accounted for about 95%; in mid-June, a study led by Professor Zhang Wenhong of Huashan Hospital Affiliated to Fudan University showed that in the After tracking more than 30,000 early non-severe Omicron-infected patients, it was found that the probability of developing severe disease in patients with mild disease was 0.065%, and the severe disease rate in the non-high-risk group was 0%.
New changes have taken place in the new crown, and clinical trials conducted according to the old standards cannot draw conclusions. For Junshi’s VV116, because the experimental group and the control group did not turn into severe disease, they could only submit “clinical improvement” as the main result of the clinical trial. The drug has not yet been approved.
CDE’s new regulations just solve the current embarrassment. The above-mentioned business people believe: “This actually encourages the research and development of new crown drugs.”
However, according to the “Guiding Principles” in February, if a company uses clinical improvement as the primary endpoint, it needs to be evaluated in combination with clinical symptoms, imaging, and etiology. It is not easy to meet this standard: In June, Shionogi’s new crown oral drug Ensitrelvir was rejected by the Japanese government because it only improved the viral load but did not reach the endpoint of “improving clinical symptoms” .
But in general, changes in clinical endpoints always leave a way for companies to survive, and many varieties have the opportunity to declare as “new crown oral drugs”. Does China need more special medicines for the new crown? It is not known whether the Food and Drug Administration has considered this issue when developing the new standard.
Does the market not need so many new crown drugs?
On August 2, the “Azvudine” of Real Bio was officially put into production, and the designed capacity is to supply more than 100 million servings per year.
On July 18, Kexing Pharmaceuticals stated at an online investor exchange meeting that the drug demand for new crown drugs can refer to the national drug reserve of influenza treatment drugs. One figure is around 26 million. If the reserves of the provincial health and health commissions and disease control departments are included, the demand may be larger.
According to the calculation of Founder Securities, if it is calculated according to the proportion of drug reserves covering 10% of the total population within three years, From 2023 to 2025, the number of new crown drugs purchased by the state will be 3,000 10,000, 50 million, and 60 million.
In other words, in terms of quantity alone, Real Bio’s products are enough to meet the national stockpile. Those still in Phase III clinical stage, or suffering fromWill the domestic new crown drugs that are waiting for approval for marketing really still be needed by the market?
In addition, CDE also gave an evaluation for the development of new crown preventive drugs, especially the currently quite hot nasal and pharyngeal sprays for new crown drug development: there are indeed nasal and pharyngeal sprays. The drug of the route has declared the indication of new coronary pneumonia. But for these products, “R&D should be done with caution.”
The Health Knowledge Bureau learned from a company engaged in the research and development of nasal spray-type new crown drugs, according to CDE, If it is preventive medicine, there may be a chance of survival; but if it is It is a therapeutic drug, and there is really no hope of approval.
On August 2, Hanyu Pharmaceutical also stated in response to investors’ questions that according to the CDE’s “Evaluation Criteria”, the new crown products of nasal and pharyngeal sprays are not suitable for The preventive indication “may have some clinical value”. The company’s new crown polypeptide nasal spray project HY3000 has significant effects on the new crown original strain, delta, and Omicron BA.1, BA.2, and BA.4, and an IND application has been submitted.
Health Knowledge Bureau has noticed that some companies have begun to explore preventive treatment indications. In May of this year, Simcere Pharma’s 3CL protease inhibitor SIM0417 was approved for clinical use for post-exposure prophylaxis and treatment of COVID-19-positive populations. However, in the same indication, Pfizer’s similar drug Paxlovid has failed once.
Existing companies have indicated to the Health and Knowledge Bureau that will conduct internal analysis on the caliber given in the “Q&A” to decide whether to further develop the product.
But now, with this document disappearing from CDE’s official website, corporate R&D strategies may have to be reset.
Writing | Gu Yue
Editing｜Jiang Yun Jia Ting
Operation | Twenty-Three
Illustration | Visual China
#New crown oral medicine##Hanyu Pharmaceutical#