The US Food and Drug Administration (FDA) formally approved the first new crown treatment drug yesterday: Remdesivir. Remdesivir can currently be used to treat patients with COVID-19 who are 12 years old and weigh more than 40 kg. It is worth noting that just last week, the World Health Organization (WHO) “Unity Trial”, including Redecive, failed. This trial failed to find an effective treatment.
The conclusions of the FDA and WHO are different. The important reason is that according to the clinical trial results of the National Institute of Allergy and Infectious Diseases, remdesivir is likely to shorten patients Recovery time, but the improvement in patient mortality is not significant. Therefore, this drug may help some patients with new crowns, but it is not a life-saving “magic drug.”
This article is from WeChat official account:Universal Science (ID: huanqiukexue) OF: Luoding Hao, from the head of FIG: unsplash
Remdesivir(Remdesivir) is currently one of the best candidates for new crown drugs. This is a drug that can interfere with virus replication. According to the National Institute of Allergy and Infectious Diseases (NIAID) at the end of April, a clinical trial involving 1062 people, Redecive Can shorten the recovery time of patients. In the trial, patients who used remdesivir took an average of 11 days to recover, but for patients who used a placebo, the number was 15.
NIAID Director Anthony Fauci(Anthony Fauci) pointed out,Although Remdesivir only shortens the recovery time by 31%, not 100%, this test shows that Remdesivir can indeed help the human body to resist the new coronavirus.
Fauci said that compared with patients in the placebo group, the mortality of patients in the remdesivir group was also lower, but the difference was not significant. However, there are significant differences in the recovery time between the two groups. This is enough to persuade researchers to terminate the trial early-since Redecivir has shown a significant effect, the trial staff must ensure that patients in the placebo group can also use the drug. In a press conference in late April, Fauci pointed out that remdesivir will become a standard treatment for new coronary pneumonia.
On October 8, just five months after the press conference, the NIAID-funded adaptive treatment trial for new coronary pneumonia (ACTT-1)< /span>The team published the final report of the Remdesivir trial in the well-known journal “New England Journal of Medicine”. In the final report, the investigator pointed out that the average recovery time of the Redecive group was 10 days, while that of the placebo group was 15 days. Although there is still no significant difference in the mortality rate of the two groups of patients, there is a significant difference in the recovery time(p <0.001). It can indeed be used to treat new coronary pneumonia. In the conclusion, the researchers stated that the conclusions of this study are consistent with the conclusions of many previous small-scale experiments. For example, Professor Wang Chen of the China-Japan Friendship Hospital published a study (237 patients) in The Lancet in the early stage of the epidemic, indicating that Reid Civir can effectively shorten the recovery time of patients with new crown; and a study published in the Journal of the American Medical Association in August showed that patients taking remdesivir are more likely to improve their symptoms within 5 days of treatment.
Compared with placebo, remdesivir can effectively shortenRecovery time of patients with new crown. Source: Beigel et al., NEJM, translation: Luo Dinghao
The University of Leeds virologist Stephen Griffin(Stephen Griffin) said, “Everyone’s eyes are on Redsiewe Because this may be our best hope at the moment.”
However, just last week, the World Health Organization (WHO)’s “Solidarity Test”(Solidarity Trial) has failed to declare (see Global Science for details Last week’s report). In the report, the WHO pointed out that the four experimental drugs, including Remdesivir, failed to significantly improve the mortality of patients with new coronary disease. This clinical trial involving more than 12,000 patients in more than 400 hospitals around the world shows that in the trial of severe patients with new coronary pneumonia led by the FDA, the mortality rate of patients receiving remdesivir therapy is about 11%. The placebo group had a mortality rate of 11.2%; the NIAID completed trial showed that after 29 days of using Redecive, the experimental group had a mortality rate of 11.4% and the control group had a mortality rate of 15.2%, but it was not statistically available. Significant difference. Eric Topol (Eric Topol), director of the American Scripps Research Institute said: “(Remdesivir) obviously did not meet people’s initial expectations.” Remdesivir’s “magic medicine” journey seemed to fall short in an instant.
The efficacy of Remdesivir is highly suspected
These conflicting information about Remdesivir have made people increasingly anxious in the past few weeks. On the early path of finding new crown therapy, small-scale clinical trials that lack a control group are verycommon. SVB Leerink Medical Investment Bank analyst Jeffrey Porgs (Geoffrey Porges) said: “I’m so tired of these uncontrollable groups. Research. It is good news that 50%-60% of patients recover and are discharged from the hospital. However, patients with new coronary pneumonia have a higher chance of recovery.” In the trial without a control group, scientists could not know whether it was Redsey. After Wei Ligong, the patient’s own immune mechanism successfully resisted the new coronavirus.
What people did not expect was that even though there are now large-scale clinical trials with a control group such as ACTT-1 and Solidarity Test, the efficacy of Remdesivir is still full of doubts: Remdesi Wei is likely to shorten the recovery time of patients, but it is still unknown whether it can improve the mortality of patients.
Just after the WHO announced the results of the solidarity trial, the manufacturer of Remdesivir, Gilead (Gilead) issued a statement . In the statement, Gilead pointed out that the results of the solidarity trial “do not match with other clinical trials” and that it has not yet been “peer-reviewed”, which is not enough to be an argument in “rigorous and constructive scientific discussions.” Therefore, Gilead refused to accept this result.
Gilead Picture source: Reuters
Faced with the uncertainty of the efficacy of Remdesivir, Fauci said that it reminded him of the AIDS therapy trial conducted in the early 1980s. In these trials, Zidovudine (AZT) only showed a general efficacy-the same as today’s remdesivir. However, researchers in ZidovudineContinuing to develop better therapies on the basis of AIDS, finally achieved today’s highly effective AIDS treatment program. The FDA’s decision yesterday to approve the use of Radixivir for the treatment of new coronary pneumonia will undoubtedly add a lot of impetus to the research of Radixivir. Fauci believes that remdesivir will have the same fate as Zidovudine, and that the former will become the standard treatment for new coronary pneumonia.
Even with Redcivir, it’s not enough
After the FDA passed the decision to use Remdesivir therapy, the first issue was the number of drugs. As early as the eve of NIAID’s clinical trials, Gilead had already begun mass production of Redecive. The report shows that based on the 10 days of remdesivir treatment for each patient, as of the end of March, the remdesivir produced by Gilead is sufficient to treat 30,000 patients. Gilead said that by further streamlining the production of remdesivir and actively looking for new sources of raw materials, they hope to produce enough remdesivir for 1 million patients by the end of this year.
Even if we have enough remdesivir, it is still not enough. The currently known mechanism of remdesivir is single: the active metabolite of remdesivir in the body is an adenosine triphosphate analogue, which mainly inhibits the replication of new coronavirus by interfering with viral RNA replicase; in addition, remdesivir Side effects of Civir are hepatitis, hypotension and dehydration. Therefore, in the long run, the best result is the development of multiple antiviral drugs, each of which has a different mechanism of action. Timothy Sheahan, a virologist at the University of North Carolina at Chapel Hill, (Timothy Sheahan) has begun to work with Gilead researchers Remdesivir conducts further research. He pointed out that the potential threat of “antiviral resistance(antiviral resistance) cannot be ignored. If we want to guard against this threat, more than just First-line drugs are needed, as well as second-, third-, fourth-, and fifth-line drugs.”
However, the development of new drugs has not been smooth sailing. Chloroquine(chloroquine) and hydroxychloroquine(hydroxychloroquine )Two anti-malarial and anti-inflammatory drugs, not onlyIn the WHO solidarity trial, there was no significant effect. In the large-scale British clinical trial Recovery in June, patients who used hydroxychloroquine had a higher mortality rate than the control group(Hydroxychloroquine group: 25.7%, control group: 23.5%).
Similar to hydroxychloroquine, two drugs for the treatment of AIDS, lopinavir(lopinavir) and ritonavir(ritonavir) also did not show a significant effect. In the Recovery clinical trial, the mortality rate of 1596 patients who received lopinavir/ritonavir treatment was not significantly different from that of 3376 control patients. Another highly anticipated therapy, the beta interferon (interferon-beta) therapy, also performed poorly in clinical trials.
However, researchers are still looking for other potential new crown drugs, and Sean is one of them. In a study published in “Science Translational Medicine”, his team found that N4-hydroxycytidine (NHC) can fight against the new crown Many coronaviruses, including viruses, even include a new type of coronavirus variant that is resistant to remdesivir. The antibody cocktail therapy developed by Regeneron (Regeron) is also attracting attention. The Regeneron team published a paper in “Science” that this therapy named “REGN-COV2” has significant effects in rhesus monkeys and golden hamsters; and the clinical trial report published on September 29 showed that REGN-COV2 The effect is significant in patients who have not developed an effective immune response to the new coronavirus.
In addition, other promising drug targets have gradually emerged. Just this Tuesday, two papers published back-to-back in “Science” pointed out that type 1 neurociliary protein (NRP-1) is a new coronavirus An important “accomplice” of invading human cells. If inhibiting NRP-1 and new coronavirus surface spike protein(Spike protein), then the efficiency of the new coronavirus invading cells will be greatly reduced.
But to determine the effects of potential therapies, researchers still need a large number of clinical trials. Fortunately, our efforts and experience today can not only save lives in this epidemic, but also make us better prepared next time we face similar difficulties.
This article is from WeChat official account:Global Science (ID: huanqiukexue), author: Luo Dinghao