I saw an exciting news today. VV116, a COVID-19 specific drug developed by my country, has passed the "head-to-head" Phase III clinical study. Its efficacy is no less than Pfizer's famous COVID-19 specific drug Paxlovid, and it is better in terms of safety. The study was published in the world's top medical journal "New England Journal of Medicine" on December 28.
The so-called "head-to-head" study is a non-placebo-controlled trial, which is a clinical trial that uses drugs or methods that have been used clinically as a control. It is a direct PK of two therapeutic drugs or methods.
is like a 100-meter race. You can run one person first and record his or her results with a stopwatch. Then another person can run again and record the results for comparison.
Two people can also be on the same track. When starts the gun and starts, they will start to PK at the same time to determine the winner. In drug clinical trials, this is called "head-to-head."
You can easily think that head-to-head research is the most convincing and can eliminate the interference of other factors.
However, head-to-head research is also time-consuming and expensive, but extremely risky.
Because if there is a disease for which there is no effective drug treatment, clinical trials can use a placebo group. Once it is shown to be effective, it can become the global standard treatment plan.
What you want to compete head-to-head is this standard solution. If it succeeds, you will become the new standard. If it fails, you will be disgraced and all your efforts will be wasted.
For example, in a 100-meter race, you need to compete with Boulder, who is the fastest. If you run within 10 seconds, which is similar to Boulder or even surpass him, you will become famous.
But if you have to run 11 seconds, a lot of people around the world can run this time, and you can only go home and farm.
In the treatment of COVID-19, Pfizer's Paxlovid achieved good results in a randomized, double-blind , placebo-controlled EPIC-HR clinical trial for non-hospitalized adult COVID-19 patients at high risk of developing severe symptoms. Compared with the placebo group, patients who received treatment within three days of symptom onset had an 89% reduction in the risk of hospitalization or all-cause death, and patients who received treatment within five days of symptom onset had an 88% reduction in the risk of hospitalization or death.
Paxlovid has thus become the World Health Organization the only drug strongly recommended for the treatment of high-risk patients, and has become the main method of treating COVID-19 in European and American countries.
VV116 is an RdRp (ribonucleic acid polymerase) inhibitor developed by Shanghai Institute of Materia Medica, Chinese Academy of Sciences, , Wuhan Institute of Virology, Chinese Academy of Sciences and other institutions. It can inhibit the replication of the new coronavirus in the human body. Like Paxlovid, it is also an anti-new coronavirus small molecule drug.
Paxlovid has been proven to be effective for high-risk patients. The PK target of VV116 is of course this new coronavirus miracle drug that has been called a specific drug.
From April 4 to May 2 this year, the drug conducted a non-inferiority single-blind (investigator-blinded) phase 3 randomized clinical trial in seven designated hospitals for COVID-19 in Shanghai, directly PKing with Paxlovid. The
trial recruited 822 adult patients with confirmed mild to moderate disease at high risk of progression and divided them into the VV116 group and the Paxlovid group. Ultimately, 384 people received VV116 treatment and 387 people received Paxlovid treatment. The primary research endpoint set in the
trial is "time to sustained clinical recovery", and secondary research endpoints include "the percentage of subjects who develop COVID-19 progression (defined as progression to severe/critical COVID-19 or all-cause death) by day 28", etc.
The results showed that VV116 achieved non-inferiority in "time to sustained clinical recovery" compared with Paxlovid, and the median recovery time in the VV116 group was shorter, only 4 days, compared with 5 days in the Paxlovid group.
Translation is that the efficacy of VV116 is not inferior to Paxlovid, and the recovery time is faster.
In terms of "time to disappearance of persistent symptoms" and "time to first nucleic acid negative result", both are similar, with the median time being 7 days.
Since no patient in either group developed severe illness or death within 28 days, there is no effective conclusion on the efficacy of preventing progression to severe illness and death.
To put it simply, VV116 has achieved an effect not inferior to Paxlovid in the treatment of high-risk mild to moderate patients in the trial. However, since there has been no severe disease or death, no conclusion can be drawn yet in terms of preventing severe disease and death.
In the original Paxlovid experiment, 0.8% of severe hospitalizations or deaths occurred in the drug group, and the rate reached 6% in the placebo group. Therefore, it was concluded that the reduction of severe illness or hospitalization was extremely obvious.
In addition, in terms of drug safety, the incidence of adverse events of VV116 is also lower than that of Paxlovid, and because Paxlovid interacts with multiple drugs, there are many contraindications for its use, such as some drugs that treat hypertension and cardiovascular disease. However, the possibility of interaction between VV116 and combined drugs is very small, so it may have more advantages in treatment.
So judging from this result, VV116 and Paxlovid should be evenly matched. This means that China’s own anti-COVID-19 small molecule drug has the potential to become a specific drug for the treatment of COVID-19 after it is launched. The drug has currently submitted a marketing application to the Food and Drug Administration.
According to media reports, VV116 has been approved for sale in Uzbekistan, priced at US$185 per box, equivalent to approximately RMB 1,248.
Pfizer also announced yesterday that it has lowered the price of Paxlovid in China to 1,890 yuan per box.
Paper:
NEJM: VV116 versus Nirmatrelvir–Ritonavir for Oral Treatment of Covid-19
