Text/ Ling Xin Xin Ying
Editor / Wang Xiao
Photo/unsplash
On April 6, 2022, Chinese pharmaceutical companies developed pharmaceutical companies (9939. HK) announced the key data of a phase III clinical trial of a new crown oral drug for the treatment of non-hospitalized new crown patients with mild and moderate diseases, saying that the drug can effectively reduce the hospitalization rate and mortality rate of new crown patients. At the opening of the day, pioneering pharmaceutical rose 200%, and as of the close, the increase in revenue narrowed to 106.37%.
The drug, called pkrutamine, gives the capital market imagination space because it is the first Chinese COVID-19 oral drug to complete a global multi-center clinical trial.
Relevant people in the development of the pharmaceutical industry told Caijing Health that it will actively promote the application for emergency drug use authorization (EUA) licenses from national drug regulatory agencies in China, the United States and other countries and regions, and the timetable will be updated in the future.
The poor results of the phase III interim clinical analysis released by pkrutamine at the end of December 2021 led to a single-day plunge of 70% in the share price of pioneering pharmaceuticals. As of now, pioneering pharmaceuticals has not yet released the complete data of Phase III.
A primary market investor revealed to Caijing Health that the Drug Evaluation Center (CDE) of the State Food and Drug Administration will organize relevant enterprises to meet in April to further promote the speed of research and development and listing of domestic new crown oral drugs. "Referring to the vaccine practice, these companies should continue to do phase III clinical trials in China, applying for emergency authorization while walking on two legs." However, for the news that a relevant meeting may be held, a CDE staff member responded that he did not know.
According to the incomplete statistics of "Finance and Economics Big Health", at present, there are 14 new crown oral drugs in China in emergency research and development, in addition to the development of pharmaceuticals, Junshi Biology, real biology oral drugs have also entered Phase III clinical trials.
Who can become China's first oral NEW CROWN drug, and when will domestic drugs be available?
Without publishing the full data, it is not easy to judge?
Lu Hongzhou, president of Shenzhen Third People's Hospital, who led a clinical trial of pucrolamine in China, told Finance and Economics Health that the Shenzhen Third People's Hospital has now enrolled dozens of patients and has shown certain effects, mainly including the reduction of clinical symptoms of new crown patients and the negative results of viral nucleic acid tests.
In a April 6 announcement, Pioneer Pharmaceuticals said that pkrutamine improved COVID-19-related symptoms, including fever, shortness of breath, and cough, and continued to improve better than the control group until at least the 28th day.
Compared with the control group, the corresponding protection rate of the pkrutamine group was 50% of the 730 subjects who had been taking the drug for at least one day; among the 721 subjects who completed the drug for more than one day, the corresponding protection rate was 71% compared with the control group; among the 693 subjects who completed the drug for more than seven days, 0 in the pkrutamine group were hospitalized, and the corresponding protection rate was 100%.
Pkrutamide showed some effect in subjects with high-risk factors. In particular, participants aged ≥ 60 years with at least one underlying medical condition, such as obesity, diabetes, hypertension, etc., significantly reduced hospitalization/mortality in the pkrutamine group compared with the control group.
At the same time, compared with the control group, the pkrutamine treatment group significantly and continuously reduced the new crown virus load from day 3 to day 28 of administration.
However, a secondary market pharmaceutical industry analyst said bluntly, "The market still has many questions about the existing published data." ”
Compared with the new crown oral drug Pfizer Paxlovid, which has been listed in China, the data currently published by pkrutamine is incomplete, and the preliminary data are slightly different. Data released by Paxlovid in December 2021 said the drug reduced the risk of hospitalization or death in COVID-19 patients by 89 percent (within three days of symptom onset) and 88 percent (within five days of symptom onset).
A pharmaceutical industry analyst introduced to "Finance and Economics Big Health", "The data of the Pkrutamine subgroup is not bad, but if the whole population does not reach the main clinical endpoint of phase III, I do not know whether the Food and Drug Administration can approve it." ”
The number of patients enrolled in Pkrutamine was 733, only one-third of Paxlovid, and the overall number of admissions was only 27 by the end of the trial. "There were only six hospitalizations in the seven-day medication control group, and the overall medication of patients has not been announced, which is difficult to rule out contingencies, such as whether patients have used other drugs at the same time, and whether they have been vaccinated?" A new drug research and development industry insider said that it is difficult to judge the success of its clinical trial results based on the data currently released by the pioneering pharmaceutical industry.
Pioneering Pharmaceuticals said that as Opichron has become a major epidemic strain in the world, the overall hospitalization rate and length of hospitalization of new crown patients are declining. For example, he was originally hospitalized for 10 days, which became five days, two or three days, and statistically showed a different situation.
Tong Youzhi, founder of Pioneering Pharmaceuticals, admitted at a performance communication meeting held at the end of March that if there is a significant difference in the improvement of hospital stays, "1,000 people may be needed."
A new drug developer judged that the more important problem is that the trial of pkrutamine released this time did not screen patients, and Pfizer enrolled high-risk patients, which is easier to make differences. "Choosing to enroll high-risk and severely ill patients also requires companies to have confidence in the safety of drugs, otherwise enrolling too many severe patients will also affect the proportion of patients who die."
However, he also pointed out that in general, the clinical trial difficulty of latecomers will be higher than that of the earliest approved drugs, in addition to the mild symptoms of the Omiljun strain infection, and the global universal vaccination has also reduced the overall number of high-risk patients.
The new drug developer believes that in the context of the transformation of Omikeron into a major epidemic strain, the endpoints of clinical trials can be adjusted accordingly, "some objective data, such as changes in viral load, can be used." If the company can fully disclose this data, it will certainly be beneficial to get approved. ”
Pioneering Pharmaceuticals said on a conference call on the morning of April 6 that the more detailed CSR report of the above clinical trial is expected to take four to six weeks to sort out, and then consider disclosing it through channels such as article publication or academic conference.
Can you stand out by taking a new technology route?
As a member of the national new crown pneumonia medical treatment expert group, Lu Hongzhou hopes that the domestic new crown oral drugs will accelerate the listing process. "In the future, it will still be based on small molecule oral drugs, which are more convenient to use and cheaper than imported ones."
At present, there is a domestic new crown drug approved for listing in China, which is made by Tengsheng Bo Pharmaceutical (2137. HK) produced antibody injections, and the Shenzhen Third Hospital also participated in relevant clinical studies. Lu Hongzhou compared the effects of the two types of drugs, said that if the antibody drugs can be used early, the viral load in the human body can drop sharply after two times, and it can also play a preventive drug, but the production cost is higher, and it needs to be infused intravenously by medical staff.
"Antibodies need to be transported in the cold chain, and once there is an outbreak in a city, the transportation capacity may not be guaranteed." The above-mentioned new drug developers further analyzed.
The earliest development of pkrutamine was not used to fight the new crown virus, but for the clinical development of metastatic castration resistance prostate cancer and metastatic breast cancer, a new generation of androgen receptor (AR) antagonists, but also ACE2 and TMPRSS2 degraders.
According to the Brazilian clinical trial data released by Pioneering Pharmaceutical in June 2021, it can reduce the mortality rate of hospitalized COVID-19 patients by 77%, and the average hospital stay time is shortened by five days. However, the results of the Phase III interim clinical analysis, released in the same year, showed that they were "not statistically significant due to the low number of events".
In the 2021 financial report of Pioneering Pharmaceutical, it was said that the sales revenue of that year reached 34.23 million yuan, which came from the down payment authorized by the external authorization of Pkrutamine new crown indications. In April of the same year, Pioneering Pharmaceutical and Huayi Taikang reached a strategic cooperation on expanding the production capacity of Pkrutamine, and in July, a cooperation agreement was reached with Fosun Pharmaceutical Industry on the commercialization of the new crown treatment of Pkrutamine in India and 28 African countries.
The R&D cost of pioneering pharmaceutical industry increased from 328.8 million yuan in 2020 to 767.9 million yuan in 2021, with a growth rate of 133.5%. The increase in R&D spending was primarily due to three Phase III global multicenter clinical trials led by the Company during the reporting period for the treatment of COVID-19.
The technical route of the development of the pharmaceutical industry is different from the two main research and development routes of the current global new crown oral drugs, the world's first two approved new crown oral drugs, Merck's monopilabvir (molnupiravir) belongs to the nucleoside class (RdRp), and Pfizer Paxlovid belongs to the 3CL protease inhibitor.
The world's first drug to receive EUA was remdesivir, a nucleotide analogue that follows the same technical route as Merck, but the drug is not an oral drug.
In addition to the development of pharmaceuticals, at present, the rapid progress of research and development of new crown oral drugs in China is the RdRp route, including Junshi Bio and Real Bio, which have entered the clinical phase III trial.
The oral nucleoside anti-coronavirus drug VV116, developed in cooperation with Suzhou Wangshan Wangshui Biomedical Co., Ltd. (hereinafter referred to as "Wangshan Wangshui"), has been approved for emergency use in Uzbekistan at the end of 2021 for the treatment of patients with moderate to severe new crown pneumonia. In China, its global multicenter Phase III clinical trial was recently launched.
The research and development progress of real organisms has attracted much attention from local governments. On February 28, 2022, Zhang Leiming, secretary of the Pingdingshan Municipal Party Committee in Henan Province, mentioned at a meeting that the new drug "azifedine" developed by Real Bio Company will soon be listed as a special anti-new crown pneumonia drug.
However, Pfizer-verified 3CL is currently the hottest technical route for new crown oral drugs. Just on January 14, with drugs from Medner and other companies on the market, Genting ShinYao announced that it has obtained an exclusive global license for a group of 3CL protease inhibitors developed by the Singapore Centre for Experimental Drug Discovery (EDDC) to treat COVID-19.
Junshi also announced that he would join the "race" around 3CL. On January 26, the Wangshan Wangshui Cooperation was announced to participate in the competition for oral anti-COVID-19 drugs targeting 3CL proteases.
Simcere Pharmaceuticals, the fastest progressing on the same track (2096. HK), announced on March 30 that its new crown oral drug SSD8432 was approved by the State Food and Drug Administration for clinical trials.
A person from a new crown oral drug research and development enterprise expects that the domestic 3CL inhibitor new crown oral drug may be listed as soon as the end of 2023.
Judging from the current research progress, the two nucleoside drugs of Junshi Bio and Real Bio and the pkrutamine of pioneering pharmaceuticals are expected to become the fastest-growing new crown oral drugs in China.
The aforementioned primary market investors speculate that companies may try to apply for EUA approval before making up for large-scale phase III clinical trials. "If further data do not validate efficacy, CDE can be discontinued at any time."
Judging from the "Technical Guidelines for Clinical Trials of New Drugs for Covid-19 Pneumonia (Trial)" released in February 2022, CDE attaches the greatest importance to mild and/or ordinary patients, which develop into the incidence or mortality of severe/critical illness.
What China needs most is an effective and solid medicine to fight COVID-19. Whoever can get the CDE recognition of the results of clinical trials first may get the "admission ticket" to the Chinese market as soon as possible.