The new coronavirus outbreak is still in progress, “I’m sick, do you have medicine?” “It’s the normal public mind, and when it comes to an infectious outbreak, it naturally turns out to be “I’m sick, do you have a vaccine?” “
And whether it has been included in the multi-national version of the “new coronary virus infection pneumonia treatment program” of the AIDS drug Lopinavir / Litonavir (Creech), or a number of domestic scientific institutions announced “candidate drugs”, or even may be prepared in “40 days of vaccines”, these days of news also seems to gradually meet the public’s expectations of a “life-saving drug” out of the world.
However, from the point of view of professional drug and vaccine research and development, it is very difficult to realize this expectation, expect ingested a drug and vaccine in a short period of time to reverse the outbreak of a new coronavirus, the prospects are far from optimistic.
So what do you think of the “potentially working” drugs and vaccines that have emerged over the past few days?
Old medicine new use, sea “sieve” medicine
“Now it’s three waves, the first wave is to screen existing old drugs, with the least risk but low success rate; the second wave is to look at some of the new drugs currently being developed in clinical research; and the third wave is the vaccine.” Dr. Chen Zhisheng, CEO of Pharma Bio, on interface news analysis.
Screening existing old drugs, in addition to the current is the fastest and most convenient way, there is a big reason that these drugs have been approved for market, or at least after a human trial, its safety data is known, compared with pure new drugs less safety risk.
This work has actually been applied in clinical clinics, with the national expert group member Wang Guangfa an interview, AIDS drug Lopinave / Litonavir (Creech) overnight burst red, and appeared in the national version of the diagnosis and treatment program.
Lopinavir/Litonavir is a compound antiviral drug used in AIDS treatment. According to Ding Sheng, dean of Tsinghua University’s School of Pharmacy, told Interface News that Lopinave/Litonaway is effective in hiv target development, and that the same target is expressed in new coronaviruses.
But this does not lead to the conclusion that Lopinavir/Litonavir is necessarily effective in treating the new coronavirus.
“The difference between the two is still quite large. Ding Sheng introduced, although the new coronavirus and HIV have the same target, but protein expression is not exactly the same, the two are only similar; To enter the problem of different organ tissue, the results of the metabolism of the drug simulated from in vitro experiments are not the same as entering the human body. “Even if the target is 100 percent, the life cycle and infestation of cells are different. “
Simply put, while HIV also has a new type of coronavirus that makes the lobinawe/Litonavir work, there are still significant differences between the two, affecting the play of The Lopinave/Litonavir.
In 2004, foreign researchers conducted clinical studies to study the role of lopinavir/litonavir on the SARS virus, including 41 SARS patients receiving a combination of Lopinavir/Litonavir and ribavirin treatment and followed up for 3 weeks. The results showed some advantages when clinical progressand and virological results were compared with 111 historical control patients treated with ribavirin alone.
Ding Sheng believes that this clinical trial is not very convincing by the summary of historical data, can carry out real-world research for further demonstration. And the interface news recently learned from a well-known domestic hospital respiratory experts, the follow-up is expected to carry out a nationwide Lopinavir / Litonawe treatment of new coronavirus multi-center randomized controlled trial. The above-mentioned experts also revealed that most of the local confirmed cases received the lopinavir/ Litonavir treatment, but not all effective, there are cured patients are not treated with the lopinavir/litonavir treatment, the effect of the drug is currently inconclusive.
In addition, there is the salt acid bromox (Mushutan), such as Bollinger Ingeheim, which is thought to be possible by binding to ACE2 receptors. Thus, the new coronavirus is inhibited, ACE2 receptor is the SARS virus and the new coronavirus and human cells binding receptor. Interface News learned that the relevant research team is currently in contact with the hospital in Wuhan, planning to carry out queue research.
In addition to its effectiveness, another concern is whether these old drugs are still effective once the new coronavirus mutates.
Current reports indicate that drugs such as The Ropinavir/Litonavir and the ebola virus drug Remdesivir, as well as Gilead’s Ebola virus drug Remdesivir, are not in the minority, but none of them have solid clinical evidence.
According to Ding Sheng, the Global Health Drug Research and Development Center (GHDDI) currently has more than 12,000 older drugs that have passed at least the first phase of the clinical phase, “based on the understanding of the new coronavirus and different screening conditions, the current screening of four targets that may work on the new coronavirus, Next to do include testing drugs and new coronavirus binding and interaction, to do functional tests, cell experiments, to see if the role of the target can act on the cells, and then study the body metabolism, to see the absorption of drugs in the body, and finally do the priority, need layers of progressive rigorous and in-depth evidence. “
In the current tight situation, there is also a need to balance time with data.
And this is only a preclinical study, in the current situation is still progressing, how to design reasonable clinical trials according to real-world patients, patient information and data collection, etc. , will still be a professional problem.
Chen Zhisheng believes that, on the whole, the screening of existing antiviral drugs, the least risk, but the probability of success is low.
New drug development? I’m afraid it’s too late.
In general, new drugs are usually developed in the face of a new disease, but in the current situation, this will be a race against time.
On January 29th, Pharmaceutical Bio announced that the company is urgently promoting the development of neutralizing antibodies for the 2019 new coronavirus (2019-nCoV), introduced through international cooperation, and preliminary studies have shown that these antibodies from global biotechnology companies can effectively neutralise new coronaviruses. The project is expected to complete the production of the first antibody samples within two months, supplying preclinical toxicology trials and preliminary human clinical trials.
Chen Zhisheng told the interface reporter, this is from the previous response to the SARS virus reserve antibodies, for the new coronavirus and SARS virus conservative site screening antibodies, through the combination of antibodies and viruses, hoping to cause downstream reactions, produce efficacy.
Pharma Bio plans to complete in vitro efficacy trials in two weeks, conduct toxicology studies in March, followed by an emergency clinical trial application (IND), and in order to shorten the clinical trial time, it plans to conduct phase 1 and 2 clinical trials simultaneously, and adopt adaptive clinical trial design. One month to complete the clinical trial. Strive for a conditional listing.
Adaptive clinical trial design is a clinical trial design that allows prior planning to modify one or more aspects of a trial based on accumulated data. The use of adaptive clinical trial design can speed up drug research and development speed, more efficient use of research and development resources, so this design has been paid attention to by the domestic and foreign pharmaceutical industry in recent years.
Time is running out, which is the biggest obstacle to the development of new drugs. In Europe and the United States, a new drug research and development generally takes ten years, although for the current outbreak, for the review and approval process will have some urgency, but as Ding Sheng said, “new drug research and development has objective laws, objective laws can not be broken.”
By the time the drug is developed, the outbreak is likely to be over. Chen Zhisheng admits that even according to his current plan, under normal circumstances also the antibody drugs of the biological organisms can not catch up with the most critical period of the outbreak.
In the current special situation, even if the regulatory efforts to shorten the approval time, but the development of new drugs can not bypass the most critical clinical trial link, which requires a certain number of patients and trial time, in order to obtain accurate and effective clinical data, confirm the safety and effectiveness of a new drug, and finally can be brought to market. And this is an important part of Ding Shengkou’s “objective law”.
Another difficulty that can not be ignored is that for the development of new coronavirus drugs, the early use of live virus research, which is very high requirements for laboratories, currently only P3, P4 laboratory can be carried out, that is, can cooperate in drug research institutions are not many.
Vaccines are also far away from water that can’t save the near fire
Another public expectation is that vaccines, if new coronavirus vaccines can be developed in time, could disrupt the spread of the epidemic.
At present, including the China Center for Disease Control and Prevention, Hangzhou National Key Laboratory, The Faculty of Microbiology of the University of Hong Kong School of Medicine Professor Yuan Guoyong, Johnson, S Microbiology, Moderna, Ai Weixin Biopharmaceutical and other domestic and foreign enterprises and research institutions have announced the launch of a new coronavirus vaccine research and development.
But it is clear that some of the previous revelations have led to public misreading.
So before the report, the National Academy of Engineering Li Lanxuan academician has said that the successful development of the vaccine at least three months, micro-organisms said that can be completed in 40 days, etc. But in fact, Li also stressed the need to “pass the national Phase I, Phase II (clinical trial) verification”, and The micro-organisms said that the 40-day preparation is only to make vaccine samples, rather than to market, or even not the time to be allowed to conduct clinical trials.
In fact, as with new drug development, vaccines take a long time from development to market, and clinical trial validation remains an integral part.
As one of the new coronavirus vaccine development enterprises, Ai Weixin director Zhang Yannan admitted to the interface reporter, under normal circumstances, the vaccine is too late to put into this outbreak, and now the development of vaccines is largely in preparation for the worst of the outbreak.
In fact, at the time of the SARS outbreak in 2003, Kexing Bio had also developed the SARS vaccine and eventually completed Phase 1 clinical trials, but by the end of Phase 1 the SARS outbreak was long over.
He told Interface News that it takes one to two years before the traditional vaccine is developed in clinical practice and four to five years at the clinical stage. The DNA vaccine technology adopted by Ai Weixin and the mRNA vaccine technology adopted by microbes are two early technologies that can quickly complete the vaccine. Zhang said that the plan is to use 4 to 6 months to bring Ai Weixin’s DNA vaccine to the clinic, including early research and development 1-2 months, safety evaluation to reduce to 2-3 months, and then submit the declaration, add up to very fast words also need 4 months.
Whether it’s DNA vaccine technology or mRNA vaccine technology, even with rapid synthesis and preparation and shorter approval times, clinical trials are not going around.
In general, the vaccine clinical trial phase 1 look at safety, phase 2 look at immunological response, that is, whether the human body can produce antibodies after being vaccinated, to achieve prevention, phase 3 to do a controlled study, to observe statistical differences. Of these, the number of Phase 3 clinical trials in the group tends to be in the thousands, or even more, even phase 2 requires hundreds of people to join the group.
At present, in order to speed up, in addition to shortening the corresponding approval time, it is possible to consider in the design of clinical programs to adopt some alternative indicators, such as in vitro and experiments.
He said some preliminary results would be announced in the next two or three weeks. But there is no doubt that the hope is that there will be a vaccine soon, rather than self-isolation at home, strengthen protection.
However, it should also be pointed out that although new drugs and vaccine development takes a long time, far from water is not quenching thirst, but the current research and development is not without practical significance.
In response, Ding Sheng said that “there can be no third (a major outbreak without special drugs and vaccines) happening again.” He argues that it is not the fault of pharmaceutical companies that the outbreak ends without enthusiasm for research and development, but that the research on prepared drugs and vaccines for potential major public health outbreaks should be sustained by state-led work.