Bavarian Nordic Submits Regulatory Filing to Expand Imvanex Use to Adolescents and Plans to Scale Production to 10 Million Doses by End-2025

On August 16, Danish pharmaceutical company Bavarian Nordic A/S (OMX: BAVA) announced that it had submitted clinical data to the European Medicines Agency (EMA), seeking to expand the indication of its Imvanex (MVA-BN) smallpox and monkeypox (mpox) vaccine to adolescents aged 12 to 17 years. The company also announced plans to increase its supply capacity to 10 million doses by the end of 2025.

Imvanex is a non-replicating live viral vaccine that utilizes the Modified Vaccinia Ankara (MVA-BN) virus, a weakened, non-replicating orthopoxvirus. Unlike traditional replicating smallpox vaccines, Imvanex does not replicate within the vaccinee’s body, offering a higher safety profile. Currently, Imvanex has been approved by the FDA and EMA for the prevention of smallpox and monkeypox in adults aged 18 years and older.

Shortly before Imvanex submitted its clinical data, the World Health Organization (WHO) reported that more than 15,600 mpox cases had been reported this year, surpassing the total number of cases from last year, with 537 deaths. The WHO declared the mpox outbreak a “Public Health Emergency of International Concern.” Regionally, the Democratic Republic of the Congo has seen a significant increase in mpox cases, and infections have been detected in several African countries that had not previously reported mpox. According to the latest reports, this wave of the mpox epidemic has spread beyond the African continent. This surge is driven by the more virulent Clade II of the monkeypox virus, which has resulted in a higher number of pediatric cases and deaths compared to the previous outbreak.

On the 16th, the World Health Organization began urging vaccine manufacturers to increase production of mpox vaccines to curb the spread of a more dangerous strain of the virus, prompting the European Centre for Disease Prevention and Control to promptly raise the risk level for mpox transmission. On the same day, China’s General Administration of Customs also issued an announcement on preventing the introduction of mpox into the country.

Affected by this news, monkeypox-related concept stocks surged across the board both domestically and internationally. According to data after the market close on the 16th, overseas markets saw Bavarian Nordic A/S soar more than 18%, Emergent BioSolutions rise nearly 24%, GeoVax Labs jump over 30%, and SIGA Technologies gain more than 11%. In China, Haichen Pharmaceutical and Yatai Pharmaceutical hit their 20% daily limits for consecutive sessions, while Life Technology, Poly Pharm, and Hefu China reached their 10% daily limits. Stocks including Bohui Innovation, Univer, Zhijiang Biology, and Maccura Biotechnology rose more than 5%. As of press time, pre-market trading for U.S. monkeypox-related stocks continued to climb.

Mpox is a viral zoonotic disease caused by the mpox virus. Sources of infection include individuals with mpox, as well as infected rodents and non-human primates such as monkeys and apes. The mpox virus is also considered a less severe variant of the variola virus (which causes smallpox). Typical symptoms include early-onset fever, rash, and lymphadenopathy, which may progress to widespread rash on the face and body. Most infected individuals recover within a few weeks, but some cases can be severe or even fatal.

Imvanex (MVA-BN) was developed by Bavarian Nordic in collaboration with the U.S. government to ensure the availability of smallpox vaccines for all populations, including immunocompromised individuals for whom traditional vaccines are not recommended. Traditional smallpox vaccines are based on replicating vaccinia virus and may cause serious adverse effects in individuals with weakened immune systems, including myocarditis, encephalitis, and vaccine-associated eczema.

In 2019, the FDA approved the MVA-BN vaccine, manufactured by Bavarian Nordic, for marketing to prevent smallpox and monkeypox infections in high-risk adults aged 18 years and older, making it the first non-replicating smallpox and monkeypox vaccine approved by the FDA. To date, Imvanex (MVA-BN) remains the first and only monkeypox vaccine approved in the United States and Switzerland (under the brand name Jynneos), Canada (under the brand name Imvamune), and the European Union/European Economic Area and the United Kingdom (under the brand name Imvanex). According to previous estimates by the World Health Organization, the efficacy of the Imvanex (MVA-BN) vaccine against monkeypox virus is 85%.

The new application submitted is primarily based on interim results from a Phase II clinical trial. The study enrolled 315 adolescents aged 12–17 years and 211 adults aged 18 years and older. The results demonstrated that the immune response following two standard doses of the MVA-BN vaccine was non-inferior in both age groups compared with other age groups, with a similar safety profile. According to the press release, approval to expand the indicated population to include adolescents aged 12–17 years is expected in the fourth quarter of this year.

Bavarian Nordic A/S is also preparing to conduct a clinical trial to evaluate the immunogenicity and safety of the MVA-BN vaccine in children aged 2–12 years, with the aim of further expanding the vaccine’s indications to younger populations. The trial is scheduled to launch later this year in the Democratic Republic of the Congo and Uganda, and may also support regulatory approval of MVA-BN in African countries and regions affected by mpox outbreaks.

Since 2022, Bavarian Nordic has been establishing a vaccine stockpile list to enhance its rapid response capability against potential disease outbreaks.

In response to the current mpox outbreak, Bavarian Nordic also plans to increase vaccine production to ensure adequate manufacturing capacity for mpox vaccines. To this end, Bavarian Nordic is working closely with the Africa Centres for Disease Control and Prevention (Africa CDC) to further expand mpox vaccine production capabilities in Africa through technology transfer to selected African manufacturers. Currently, Bavarian Nordic has supplied 2 million doses and, in addition to existing orders, has the capacity to produce 10 million doses by the end of 2025.

Meanwhile, HERA (the Health Emergency Preparedness and Response Authority), PAHO (the Pan American Health Organization), and multiple governments and organizations are collaborating with Bavarian Nordic. Recently, HERA announced the procurement of 175,420 vaccine doses from Bavarian Nordic for donation to the Africa Centres for Disease Control and Prevention (Africa CDC). Bavarian Nordic will also donate 40,000 doses of mpox vaccine to HERA, which will ultimately be donated to the Africa CDC. Additionally, Gavi, the Vaccine Alliance, the World Health Organization (WHO), and the United Nations Children’s Fund (UNICEF) have jointly donated 15,000 vaccine doses to support epidemic response in Africa. Through these various collaborations, Bavarian Nordic has supplied over 15 million doses of mpox vaccine to more than 76 countries worldwide between 2022 and 2023.

Amid the rising number of cases, the Congolese government has recently approved two mpox vaccines: Japan’s LC16 and Bavarian Nordic’s MVA-BN vaccine.

The LC16 vaccine, produced by KM Biologics under Japan’s Meiji Group, is derived from the attenuated Listera (Elstree) strain and has been approved in Japan since 1975 for active immunization against smallpox. In August 2022, Japan expanded the vaccine’s indications to include prevention of mpox. Currently, LC16 is the only smallpox vaccine globally approved for use in children.

In addition, in 2022, Russia approved the OrthopoxVac (VACΔ6) vaccine for the prevention of smallpox, monkeypox, cowpox, and vaccinia virus infections. Developed by the State Research Center of Virology and Biotechnology VECTOR in Russia, this fourth-generation smallpox/orthopoxvirus vaccine is based on the vaccinia virus. It has currently been included in the World Health Organization’s list of recommended vaccines for monkeypox.

From an R&D perspective, global mpox vaccine development pathways include live attenuated vaccines, mRNA vaccines, recombinant protein vaccines, viral vector vaccines, DNA vaccines, and fourth-generation vaccines. Among these, significant progress has been made in the areas of live attenuated vaccines, mRNA vaccines, and recombinant protein vaccines.

Currently, the mpox vaccine with the most rapid progress in China is the replication-deficient Tiantan strain mpox vaccine, jointly developed by the Beijing Institute of Biological Products under China National Biotec Group (CNBG) and the Chinese Center for Disease Control and Prevention (China CDC). The application for clinical trials was formally accepted by the Center for Drug Evaluation (CDE) of the National Medical Products Administration on July 13, 2023.

In the field of mRNA, Yang Xiaoming’s team at Sinopharm announced the development of three candidate mRNA vaccines against monkeypox, designated VGPox 1–3. Featuring a unique antigen design, these vaccines strongly induce poxvirus-specific antibodies in immunized mice. They offer a superior safety profile compared to existing live-attenuated viral vaccines and elicit neutralizing antibodies for viral prevention at an earlier stage.

A team led by Associate Researchers Zha Gaofeng and Zhan Xiaoyong from The Seventh Affiliated Hospital of Sun Yat-sen University has developed a multivalent mpox mRNA vaccine. Challenge studies demonstrated 100% protection in mice against orthopoxvirus infection, with multiple indicators confirming its favorable safety profile. These research findings have been published in Antiviral Research.

In the field of recombinant protein vaccines, Gao Fu’s team at the Institute of Microbiology, Chinese Academy of Sciences, designed a “two-in-one” monkeypox virus recombinant protein vaccine—DAM. This vaccine achieves comprehensive protection against both infectious viral particles of the monkeypox virus using a single immunogen, with a neutralizing capacity against the monkeypox virus that is 28 times greater than that of traditional live-attenuated vaccines.

According to incomplete statistics, there are more than 30 ongoing clinical trials related to monkeypox worldwide.