Olmotevirumab injection is approved for marketing, adding a new option for passive immunization against rabies virus

Recently, a recombinant human anti-rabies virus monoclonal antibody injection for the prevention of rabies, omitevirumab injection (English name: Ormutivimab Injection; trade name: Xunke), was approved by the National Medical Products Administration of China (NMPA).
) approved for marketing for passive immunization of adults exposed to rabies virus
.

Screenshot source: NMPA official website

According to public information, omitevirumab injection is mainly used in combination with human rabies vaccine to supplement the antibody gap in the active immunization process of human rabies vaccine, which can directly neutralize rabies virus in the body and play a passive immune role.
Passive immunization of patients who are bitten or scratched by rabies or other rabies-susceptible animals
.

The approval of the drug provides a new option for passive immunization of rabies virus exposed persons

What is rabies virus exposure?

What is rabies virus exposure?

Rabies virus exposure refers to being bitten, scratched, licked mucous membranes or damaged skin by rabies, suspected rabies, or host animals whose rabies is uncertain, or open wounds or mucous membranes that come into direct contact with saliva or tissue that may contain rabies virus
.

In addition, in rare cases, rabies virus can be acquired through organ transplantation or inhalation of aerosols

According to the nature and severity of exposure, rabies virus exposure is divided into three levels
.

Class I exposure refers to people who meet one of the following conditions:

(1) touching or feeding animals;

(2) Intact skin is licked;

(3) Intact skin contacts the secretions or excreta of rabies animals or human rabies cases
.

Class II exposure refers to people who meet one of the following conditions:

(1) The bare skin is nibbled;

(2) Minor scratches or abrasions without bleeding
.

Level III exposure refers to people who meet one of the following conditions:

(1) Single or multiple bites or scratches that penetrate the skin ("penetration" means at least the dermis and blood vessels have been injured, and the clinical manifestations are visible bleeding or subcutaneous tissue);

(2) The damaged skin is licked (pay attention to the tiny skin damage caused by various reasons such as chapped skin and scratching);

(3) The mucous membrane is contaminated by animal saliva (such as being licked);

(4) Exposure to bats (post-exposure prophylaxis should be considered when contact between humans and bats occurs, unless the exposed person excludes exposure to bites, scratches, or mucous membranes)
.

What is passive immunity?

What is passive immunity?

There is currently no effective treatment for rabies
.

After exposure to rabies virus, almost 100% of people die

However, although exposure to rabies virus is fatal once clinical symptoms appear, vaccines, drugs and technologies to prevent death from rabies already exist
.

Rabies is 100% avoidable as long as the vaccine is fully vaccinated and antibodies are produced in the body before the onset of the disease

At present, the prevention of rabies mainly includes active immunization and passive immunization:

Active immunity means that the body can actively produce antibodies to obtain immunity, which is mainly obtained through vaccination and lasts for a relatively long time
.

Typically, rabies vaccines take 1-2 weeks to induce antibodies, but antibodies persist for years

Passive immunity refers to the specific immunity obtained by the body passively receiving antibodies, sensitized lymphocytes or their products.
It is characterized by rapid effect, no incubation period required, and immunity can be obtained immediately after input, but the maintenance time is short
.

The period after exposure to rabies virus, before the induction of antibody production by the vaccine, is often referred to as the "active immunization-induced protective void" or "high-risk infection period"
.

At this time, the use of passive immune preparations can provide immune protection during this high-risk period, and can locally obtain a high concentration of neutralizing antibodies in the wound to block the spread of the virus in the wound

The World Health Organization's Expert Advisory Committee on Rabies recommends that for people exposed to rabies virus grade III, the wound should be thoroughly cleaned while vaccinating, and passive immune preparations should be injected around the infiltration to prevent the virus from entering the nerve tissue and obtain rapid protection.

.

In addition, for exposed persons with severely weakened immune function, passive immunization preparations should be used in combination even with grade II exposure

Efficacy and safety verified

Efficacy and safety verified

Olmotevirumab injection contains high titer anti-rabies virus monoclonal antibody NM57 (IgG1 subtype), which can specifically neutralize the linear neutralizing antigenic epitope in the conserved antigenic site I of rabies virus glycoprotein, thereby preventing Rabies virus infects tissue cells and plays a role in preventing rabies

In a randomized controlled phase 3 clinical trial, researchers evaluated the efficacy and safety of omitevirumab in combination with human rabies vaccine in people with suspected level III rabies virus exposure and a control group of marketed rabies Human immunoglobulin (HRIG) combined with human rabies vaccine

The results of this study showed that the post-exposure prophylaxis of omitevirumab combined with human rabies vaccine in the class III suspected rabies virus exposure population achieved the primary efficacy and secondary efficacy endpoints, and the safety was good, reaching the goals set by the program.
The experimental drug recombinant human anti-rabies virus monoclonal antibody injection is safe and effective
.

All in all, once exposed to rabies virus, the fatality rate is close to 100%; however, through preventive measures such as active immunization and passive immunization, 100% of rabies can be prevented
.

We expect that with the arrival of omitevirumab, more treatment options for rabies virus exposure can be provided to prevent the occurrence of rabies
.

References

[1] Olmotevirumab injection was approved for marketing.
Retrieved Feb 9,2022, from https:// China CDC issued "Technical Guidelines for Rabies Prevention and Control (2016 Edition)".
Retrieved Feb 9, 2022, from https:// Announcement of North China Pharmaceutical Co.
, Ltd.
on the results of Phase III clinical trials of recombinant human anti-rabies monoclonal antibody injection.
Retrieved Feb 9, 2022, from https://pdf.
dfcfw.
com/pdf/H2_AN202004081377778430_1.
pdf

[4] Frequently asked questions about rabies for the General Public.
Retrieved Sep 28 ,2020, from https:// sfvrsn=ac59055f_4