NEJM heavy: The phase III clinical data of the domestic new crown drug VV116 was released, and the effect was not inferior to Paxlovid, and it was safer

The COVID-19 pandemic caused by the new coronavirus (SARS-CoV-2) is still spreading rapidly around the world, and SARS-CoV-2 has evolved into the mutant Omicron with stronger transmissibility and immune evasion, and the widespread and timely distribution of effective antiviral drugs is an important measure
to cope with and suppress the pandemic.

In December 2021, the US FDA approved Pfizer's Paxlovid for the treatment of mild to moderate COVID-19, which acts as an antiviral
by targeting the new coronavirus's 3CL protease (3CLpro).
But at present, Paxlovid is undersupplied and below global demand
.

VV116 is a new oral nucleoside anti-new coronavirus small molecule drug
jointly developed by the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Wuhan Institute of Virology, Chinese Academy of Sciences, and Xinjiang Institute of Physical and Chemical Technology, Chinese Academy of Sciences.
It has oral bioavailability and anti-SARS-CoV-2 effective activity in animal experiments, with a satisfactory safety profile
in early clinical trials.
However, the efficacy of VV116 in clinical recovery, symptom relief, and prevention of disease progression remains unknown, particularly compared
to Paxlovid.
In addition, the safety of VV116 has not been fully evaluated
.

On December 28, 2022, the New England Journal of Medicine (NEJM) published a research paper
titled: VV116 versus Nirmatrelvir–Ritonavir for Oral Treatment of Covid-19.

This phase 3 randomized controlled trial comparing the effects of the domestic novel coronavirus drug VV116 with the Pfizer new crown drug Paxlovid head-to-head showed that VV116 was not inferior to Paxlovid in terms of time to sustained clinical recovery in adult patients with mild to moderate COVID-19 with high-risk factors (4 days vs.
5 days; Risk ratio was 1.
17), and there were fewer
adverse events.

The clinical trial was led by Professor Zhao Ren of Shanghai Ruijin Hospital, Professor Gaoyuan of Shanghai Renji Hospital and Academician Ning Guang of Shanghai Ruijin Hospital and was carried out
in 7 Shanghai hospitals.
This is also the first domestic oral antiviral drug head-to-head Phase 3 clinical trial
for COVID-19 patients during the Omicron epidemic.
VV116 is a small molecule inhibitor
targeting RNA polymerase (RdRp) that targets the new coronavirus RNA-dependent RNA polymerase (RdRp) jointly developed by the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Wuhan Institute of Virology, Xinjiang Institute of Physical and Chemical Technology, etc.

Many countries, including my own, have approved emergency use authorizations
for Paxlovid for the treatment of COVID-19.
However, its supply cannot meet global demand
.
VV116 is a domestic oral antiviral drug with effective anti-SARS-CoV-2 activity
.

Professor Zhao Ren of Shanghai Ruijin Hospital, Professor Gaoyuan of Shanghai Renji Hospital and Academician Ning Guang of Shanghai Ruijin Hospital led this phase 3 randomized trial
of non-inferiority and observer blinding during the Omicron epidemic.
Patients with symptomatic mild to moderate COVID-19 who are at high risk of progression are assigned to receive a 5-day course
of VV116 or Paxlovid.
The oral dose of VV116 is 600 mg every 12 hours on day 1 and 300 mg
every 12 hours on days 2-5.
The oral dose of Paxlovid is 300 mg Nirmatrelvir + 100 mg Ritonavir every 12 hours for 5 days
.

The primary endpoint was time up to day 28 to ongoing clinical recovery
.
Ongoing clinical recovery is defined as relief of all COVID-19-related target symptoms to a total score of 0 or 1 for the sum of each symptom and for two days (scores ranging from 0-3, with higher scores becoming more severe).

The lower bound of the bilateral 95% confidence interval greater than 0.
8 on both sides of the hazard ratio is considered non-inferior, and the hazard ratio > 1 indicates that VV116 has a shorter
time to sustained clinical recovery than Paxlovid.

In this clinical trial, a total of 771 new crown patients participated (23.
4% of them did not receive the new crown vaccine; 92.
1% of participants were mild, participants were aged 18-94 years, with a mean age of 53 years and 37.
7% aged 60 years and older), of which 384 were treated with VV116 and 387 with Paxlovid
。 In the initial analysis, non-inferiority between VV116 and Paxlovid was demonstrated in terms of time to sustained clinical recovery (hazard ratio 1.
17, 95% confidence interval 1.
01 to 1.
35) and remained unchanged in the final analysis (median, 4 days for VV116 and 5 days for Paxlovid; hazard ratio 1.
17, 95% confidence interval 1.
02 to 1.
36).

In the final analysis, there was no significant difference
between the VV116 treatment group and the Paxlovid treatment group in the time to sustained symptom relief (0 points for 11 COVID-19-related target symptoms for two consecutive days) and the time to first negative SARS-CoV-2 test.
As of day 28, no participants in either group had died or developed severe disease
.
In addition, the rate of adverse events in the VV116 treatment group was lower than in the Paxlovid treatment group, which was 67.
4% and 77.
3%
in the latter group.

Overall, the results of this head-to-head Phase 3 clinical trial showed that VV116 was not inferior to Paxlovid in terms of time to sustained clinical recovery in adult patients with mild to moderate COVID-19 with high-risk factors, with fewer
safety concerns.