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Junshi VV116 Announces Phase III Clinical Data for the First Time!

 Last Update: 2023-02-03
 Source: Internet
 Author: User

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On December 29, Junshi Biologics' oral nucleoside anti-novel coronavirus (SARS-CoV-2) drug VV116 (JT001) was head-to-head Pfizer Paxlovid Phase III clinical data on treatment with mild to moderate COVID-19 infection with progression to severe COVID-19 including risk factors for death are available in the top international journal NEJM On the blockbuster release!

Nucleoside anti-novel coronavirus (SARS-CoV-2) drug VV116 (JT001) head-to-head Pfizer Paxlovid Phase III clinical data on treatment with mild to moderate COVID-19 infection with progression to severe COVID-19 including risk factors for death are available in the top international journal NEJM On the blockbuster release! Phase III clinical data with mild to moderate COVID-19 infection with progression to severe COVID-19 including risk factors for death, the top international journal NEJM On the blockbuster release!

This is NEJM Published the first clinical trial
of China's self-developed new crown innovative drug.
Under today's epidemic situation, "one medicine is difficult to find" has always been a problem that countless people are anxious about
.
The antiviral drugs approved for the new crown in China are currently only Pfizer Paxlovid and real biological azvudine, but to date there has been no phase III clinical release
of a head-to-head small molecule drug for domestic COVID-19 patients during the Omicron variant epidemic.

This is NEJM Published the first clinical trial
of China's self-developed new crown innovative drug.

Junshi is in the year 5 The clinical study was announced as a success last month, and today detailed data is finally available
.
The results showed that the study met the non-inferior endpoint of the design, compared with PAXLOVID, the VV116 group had shorter clinical recovery times and fewer
safety concerns.

Junshi is in the year 5 The clinical study was announced as a success last month, and today detailed data is finally available
.
The results showed that the study had a shorter clinical recovery time to the designed non-inferior endpoint and fewer
safety concerns.

Below, let's take a look at the specific data
.

The efficacy is not inferior, and the safety is better

The study, led by Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, is a multicenter, single-blind (investigators remain blinded), randomized, controlled III Phase clinical trial (NCT05341609) was jointly conducted in 7 designated hospitals in Shanghai from April 4 to May 2, 2022 , a total of 822 adult patients with mild to moderate COVID-19 confirmed to be at high risk of progression were assigned to VV116 and PAXLOVID in a 1:1 ratio Group
.
In the end, a total of 771 (full analysis set, FAS) patients were treated
with VV116 (n=384) or PAXLOVID (n=387).

Among them, the median age of FAS patients was 53 years old (range: 18~94), women accounted for 50.
2%, and mild patients accounted for the proportion 92.
1%, 75.
7% of patients were fully vaccinated or received a booster shot, and 77.
3% of patients showed symptoms RECEIVED VV116 OR PAXLOVID WITHIN 5 DAYS
.

Proportion of patients with mild disease 92.
1%, 75.
7% of patients were fully vaccinated or had received a booster shot, and 77.
3% of patients showed symptoms RECEIVED VV116 OR PAXLOVID WITHIN 5 DAYS

The most common risk factors in patients included age ≥ 60 years (37.
7%), cardiovascular disease (including hypertension) (35.
1%), obesity, or overweight BMIs ≥ 25 (32.
9%), current smoking (12.
5%) and diabetes (10.
1%)
.

The primary endpoint of the study was time from randomization to sustained clinical recovery, with a lower 95% confidence interval (CI) of >0.
8 on both sides of the risk ratio (HR).
Defined as non-inferiority
.
Secondary efficacy endpoints included the proportion of patients who progressed to severe/critical COVID-19 or all-cause death by day 28, COVID-19 Change in relevant symptom scores and WHO Clinical Progress Scale scores, time to resolution of persistent symptoms, SARS-CoV-2 Nucleic acid negative time, etc
.
Safety endpoints included adverse events (AEs) and serious adverse events (SAEs
).

The primary endpoints of the study were time from randomisation to sustained clinical recovery, and secondary efficacy endpoints included

According to the final analysis results (as of August 18, 2022), VV116 was associated with PAXLOVID in the FAS population Non-inferior efficacy was achieved in "time to sustained clinical recovery" (HR=1.
17, 95% CI: 1.
02~1.
36), and the median recovery time was shorter (4 days) in the VV116 group than in the PAXLOVID group vs.
5 days).

Based on final analysis results (as of August 18, 2022)

Final analysis of sustained clinical recovery time in the FAS population

The VV116 and PAXLOVID groups performed similarly in terms of "time to disappearance of persistent symptoms" and "time to first SARS-CoV-2 nucleic acid negative", with a median time of 7 days
.
AT EACH PRESET TIME POINT (DAYS 5, 7, 10, 14, 28), THE PROPORTION OF PATIENTS IN SYMPTOM RESOLUTION IN THE VV116 GROUP WAS HIGHER THAN IN THE PAXLOVID GROUP
.
Progression to severe/critical disease occurred in either group COVID-19 or death
.

In addition, about three-quarters of the patients in this study had been vaccinated against the new crown, and such patients would have been excluded in most studies, subgroup analysis showed VV116 THERE WAS NO STATISTICALLY SIGNIFICANT DIFFERENCE
IN TREATMENT OUTCOMES WITH PAXLOVID IN VACCINATED OR UNVACCINATED PEOPLE.

About three-quarters of the patients in this study had been vaccinated against the new crown, and such patients were excluded in most studies

In terms of security, VV116 has fewer
security concerns than PAXLOVID.
THE INCIDENCE OF AE WAS LOWER IN THE VV116 GROUP THAN IN PAXLOVID Groups (AE for all levels: 67.
4% vs.
77.
3%, grade 3 or 4 AE: 2.
6% vs.
5.
7%)
.

In terms of security, VV116 has fewer
security concerns than PAXLOVID.

NOTABLY, PAXLOVID INTERACTS WITH MULTIPLE DRUGS, AS OPPOSED TO VV116 It does not inhibit or induce major drug-metabolizing enzymes, or inhibit major drug transporters, so interactions with concomitant drugs are less
likely.

Expand patient coverage

In the press release of Junshi said, Dr.
Zou Jianjun, President of Global R&D, said that after this research that has been highly recognized by the international academic community, Junshi continues to invest The clinical development of VV116 for indications in other populations provides better and safer treatment options
for new crown patients in China and even around the world.

Junshi continues to invest VV116 works on clinical development of indications in other populations

Timeline of the development process of Junshi VV116

Screenshot from: Insight database (http://db.
dxy.
cn/v5/home/)

For example, also for patients with mild to moderate COVID-19, Junshi launched III in October The phase clinical study (registry number: NCT05582629) was double-blind, placebo-controlled
.
Patients included in this trial do not necessarily have to be at high risk for COVID-19 Patients, which means that the trial can be participated in a relatively wider
population.

Double-blind, placebo-controlled
.

The PI of the study was Li Lanjuan, an academician of the Chinese Academy of Engineering, and the primary endpoint of the study was the duration
of clinical symptoms until resolution.
The target enrollment is 1200 and is currently recruiting
.

NCT05582629 Trial design, endpoint indicators, inclusion criteria

Screenshot from: Insight database

Junshi is also exploring the rebound rate of VV116 in mild to moderate coronavirus infection, and just registered a head-to-head Paxlovid on December 19 The phase III clinical trial (registration number: ChiCTR2200066811) was presided over
by Academician Ning Guang, President of Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine.
The primary endpoint of the study was post-randomization 60 rebound rate within days, with a target enrollment of 478 people, and the trial
is expected to be completed in December 2023.

Mild to moderate coronavirus rebound rate

ChiCTR2200066811 Clinical Trial Information

From: Insight Database Web

In addition to mild to moderate patients, Junshi registered an international multi-center for moderate to severe COVID patients on ClinicalTrials.
gov in March this year III Clinical Study (CAS: NCT05279235), a multicenter, double-blind, randomized study
comparing efficacy and safety with Favipiravir.
However, in ClinicalTrials.
gov website shows that recruitment has not yet begun for the study
.

Patients with moderate to severe new crown disease

NCT05279235 Trial design and intervention protocol

From: Insight Database Web

Junshi also prepared
for post-launch production early.
In May this year, Junshi announced that it has reached a cooperation agreement with Hisun to entrust the production of VV116 API
.

When will the new crown antiviral drug "one drug is difficult to find" be solved? A large number of domestic enterprises are in the sprint

At present, the new crown epidemic continues to spread rapidly around the world, and the transmission and escape ability of the virus continues to increase
with mutations.
Oral antiviral drugs are considered to be one of
the indispensable prevention and control methods for fighting the epidemic because of their advantages of convenient administration, high drug resistance barrier, and few transportation and storage restrictions.

Oral antiviral drugs are considered to be one of
the indispensable prevention and control methods for fighting the epidemic because of their advantages of convenient administration, high drug resistance barrier, and few transportation and storage restrictions.

However, at present, accessibility and safety reasons are still one of the many factors that limit the use of
drugs.
Such as Pfizer Paxlovid, its approved scope is spread across many countries around the world, there is a state of short supply, and there are even rumors that Pfizer's genuine P drug has been speculated at a high price of tens of thousands of yuan, and the "Indian generic drugs" whose quality is difficult to guarantee are also going their own way
.

However, at present, accessibility and safety reasons are still one of the many factors that limit the use of
drugs.

The advent of more new drugs, especially domestic new drugs, is undoubtedly an important solution
to support the current domestic new crown treatment and alleviate new crown anxiety.
VV116 with the results announced this time It is one of the best, and other new drugs have recently released positive signals
.

According to the Insight database, the current research and development of domestic new crown small molecule drugs is mainly focused on
the two targets of 3CLPRO and RDRP.

3CLPRORDRP

Global heat map of new crown drug targets

Screenshot from: Insight Database Global New Drug Module (http://db.
dxy.
cn/v5/home/)

Typical representatives of RDRP targets, the imported drug dimensions are Molnupiravir (Merck), remdesivir (Gilead), and domestic drugs to Junshi VV116, real biological azvudine is the mainstay
.
Currently in the country, Azvudine has been approved, Molnupiravir Listing application is pending
.
As positive clinical results for VV116 continue to be released, when is it expected to be available?

RDRP targets: Molnupiravir (Merck), remdesivir (Gilead), Junshi VV116 Real Bio Azvudine

3CLPRO targets are more sought after by pharmaceutical companies
.
3CLPRO RNA in novel coronaviruses It plays an important role in replication and is highly conservative, and the representative of this target is Pfizer's star drug Paxlovid, which is the only approved 3CL protease inhibitor in China; As well as Shiono's Ensitrelvir, which is in the process of market application, has joined hands with Shanghai Pharmaceutical
.

3CLPRO target Pfizer Paxlovid Shiono Ensitrelvir

Paxlovid and Azvudine have been temporarily included in the medical insurance payment scope as the ninth version of the new crown diagnosis and treatment plan, Paxlovid 2300 yuan / box, Azvudine 270 Yuan/bottle
.
However, due to the late approval of the new crown indication of azvudine, only Pfizer's Paxlovid
has passed the preliminary review of medical insurance and will strive for the access of the new crown indication of the official medical insurance catalog this year.

Due to the epidemic in December, the medical insurance negotiations were postponed for more than 1 month, but it has been confirmed that the 2022 medical insurance negotiations will be on January 5 ~ 8 Sunday, especially the results of the new crown drug negotiations have attracted more attention
.
Recently, Paxlovid has also lowered the online price in various provinces, from 2300 yuan / box to 1890 Yuan/box
.
How much will the price be reduced in the follow-up national talks?

How much will the price be reduced in the follow-up national talks?

Pfizer Medicare negotiation information PPT

Screenshot from: Public information of the Health Insurance Bureau

Among the domestic drugs, the 3 fastest progressing are Simcere Pharmaceutical SIM0417, Forbutevir of Frontier Biologics, Zhongsheng Pharmaceutical RAY1216
。 Simcere Pharmaceutical has completed the enrollment of all phase II/III clinical patients and is accelerating its progress towards the first domestic 3CL protease inhibitor
.

Simcere Pharmaceutical's SIM0417 Frontier Biologics of Forbutvir Pharmaceuticals RAY1216

The phase II/III clinical study was conducted in 43 clinical research centers in 20 provinces, municipalities and autonomous regions in China, and was completed within four months since the first enrollment on August 19, 2022 1208 patients were enrolled, also for Chinese patients
with the Omicron strain.

SIM0417 R&D progress Gantt chart

Screenshot from: Insight database

At present, domestic pharmaceutical companies are accelerating the development of new crown small molecule antiviral drugs to cope with the complex and severe
situation of the epidemic.
According to the Insight database, there were 4 in December alone The domestic new crown small molecule drug has been promoted to a new stage, involving stone medicine, Salubris Pharmaceutical, Guangshengtang, and Zhongsheng Pharmaceutical
.

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