The first domestically produced special medicine for COVID-19 is effective against the "worst variant"!

"We just got the results yesterday, and the ambavir/romidevir combination therapy showed a good viral inhibition effect on the Omicron variants BA.4 and BA.5." On July 8, my country's first independently developed new coronavirus treatment drug, ambavir/romidevir combination therapy, held a launch conference. Professor Lu Hongzhou, President of Shenzhen Third People's Hospital, introduced at the meeting that laboratory pseudovirus studies showed that the antibody concentration required for the drug to inhibit 90% of BA.4 or BA.5 viruses is very low (16.61μg/ml), which can meet the effectiveness standards set by the FDA.

In addition, in past clinical treatments, the combination therapy of ambavir/romisvir has also shown impressive results. Zhong Nanshan, an academician of the Chinese Academy of Engineering, said at the meeting that based on the observations of clinicians, the combination therapy can quickly reduce high viral loads in a relatively short period of time (2 to 3 days). Therefore, the combination therapy is very effective in treating patients with high viral loads.

So, how does the first domestically produced special medicine for COVID-19 remain “timeless”?

The best “antibody pair”

The novel coronavirus is still mutating, and the mutated Omicron BA.5 has a strong ability to escape the immune system, which is called the worst version of the mutant strain seen so far by American scholars. For neutralizing antibody drugs, the biggest concern is that the virus escapes after mutation.

Since neutralizing antibody drugs are designed for specific targets on the viral S protein, if the new coronavirus mutates at the drug target, the drug will become completely ineffective.

"Previously, neutralizing antibody drugs developed by several multinational pharmaceutical companies have lost their inhibitory activity against Omicron variants and have been discontinued from clinical use." Lu Hongzhou said that the first domestically produced neutralizing antibody drug has withstood the test in inhibiting Omicron variants. It not only demonstrated the ability to inhibit Omicron BA.4 and BA.5 in the latest in vitro experiments, but also demonstrated the inhibitory effect on Omicron BA.1 and BA.2 in clinical practice.

Why do domestically produced neutralizing antibody drugs remain effective despite the "huge changes" of the new coronavirus?

Zhang Linqi, head of the R&D team and professor at Tsinghua University School of Medicine, introduced the trick at the meeting: Everyone uses the method of screening "antibody pairs" to avoid being escaped by the virus, but the screening of "antibody pairs" is particular. "The two antibodies must cooperate with each other and be able to play a combination punch, for example, to identify different locations of the virus." Zhang Linqi said that the screening was very entangled, but based on the detailed study of the entire virus-antibody interaction process, he finally screened out the "antibody pairs" that can coordinate with each other in time and space to inhibit the virus from 206 candidate antibodies, and found the "best partner".

Several medication advantages

In terms of medication, this combination therapy has significant advantages in terms of duration of effect, duration of medication, and sustained effectiveness.

"It takes effect very quickly." Zhang Linqi introduced that the team found the optimal dosage through research, so that the two antibodies can reach very high levels within a few hours of injection into the body, so the drug takes effect very quickly.

"One injection can last for a long time in the body." Zhang Linqi said that due to years of experience and lessons learned in antibody research and development, the team has made a series of optimizations to the antibody, which has extended its half-life in the body by 3 to 4 times. Compared with the 5 to 7-day treatment course of small molecule drugs, neutralizing antibodies can still maintain sufficient concentration in the body to kill viruses 3 weeks after injection.

In addition, the duration of use of this combination therapy is relatively relaxed. "The replication of the new coronavirus is more obvious in the early stage, and the earlier the small molecule antiviral drugs are used, the better the effect. Generally, they are used within 5 days of positive results. However, we can still achieve good results by using these two antibody drugs within 6 to 10 days, so the clinical adaptability range of patients is relatively wide," said Lu Hongzhou.

On the same day, Brii Biopharma and its holding company Brii Biopharma announced that its long-acting COVID-19 neutralizing antibody ambavir and romisvir combination therapy was commercialized in China. The combination therapy was approved for marketing by the National Medical Products Administration on December 8, 2021, and was included in the "New Coronavirus Pneumonia Diagnosis and Treatment Plan (Trial Version 9)" in March 2022.

Source: Science and Technology Daily