KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE: MRK), known as MSD outside the United States and Canada, today confirmed that four African countries, including the Democratic Republic of the Congo (DRC), have approved ERVEBO (pronounced er-VEE-boh). ERVEBO was granted a conditional marketing authorization by the European Commission on November 11, 2019 and approved by the U.S. Food and Drug Administration (FDA) on Dec. 20, 2019. In the United States, ERVEBO is indicated for the prevention of disease caused by Zaire ebolavirus in individuals 18 years of age and older. The duration of protection conferred by ERVEBO is unknown. ERVEBO does not protect against other species of Ebolavirus or Marburgvirus. Effectiveness of the vaccine when administered concurrently with antiviral medication, immune globulin (IG), and/or blood or plasma transfusions is unknown.
Approvals by these African countries signify continued, groundbreaking progress in advancing the future of global public health preparedness against Zaire ebolavirus disease, made possible by the unprecedented collaboration between the World Health Organization (WHO), the African Vaccines Regulatory Forum (AVAREF), African governments, the European Medicines Agency (EMA), and Merck. These approvals were the result of the successful implementation of the WHO’s Roadmap for introduction and roll‐out of Merck rVSV-ZEBOV Ebola virus disease vaccine in African countries. The roadmap, designed to coordinate actions and contributions toward the licensing and roll-out of ERVEBO, helped facilitate near-parallel regulatory reviews and led to the approvals of the vaccine in several at-risk countries within 90 days of WHO prequalification.
“We are grateful for WHO’s leadership in establishing a path forward for expediting the prequalification and licensing of this vaccine in countries at greatest risk,” said Kenneth C. Frazier, chairman and chief executive officer, Merck. “This important milestone is one more example of the partnership that has formed in response to the outbreaks. While we are far from finished in the Ebola fight, this milestone shows what can be done when we work together to address the most challenging diseases that threaten people and communities.”
ERVEBO has now been registered by National Health Authorities in the following countries in Africa – DRC, Burundi, Ghana, and Zambia. Approvals in additional countries in Africa are anticipated in the near future.
As previously announced, Merck is working to initiate manufacturing of licensed doses and expects these doses to start becoming available in approximately the third quarter of 2020. Merck is working closely with the United States government, WHO, UNICEF, and Gavi (the Vaccine Alliance) to plan for how eventual, licensed doses will support future public health preparedness and response efforts against Zaire ebolavirus disease. In the meantime, Merck continues to work urgently with WHO and partners to make investigational Ebola Zaire vaccine (V920) doses available in support of international outbreak response efforts in the DRC and neighboring countries.
Selected Safety Information for ERVEBO
Do not administer ERVEBO to individuals with a history of a severe allergic reaction (e.g., anaphylaxis) to any component of the vaccine, including rice protein.
WARNINGS AND PRECAUTIONS
Management of Acute Allergic Reactions
Among 15,399 subjects vaccinated with ERVEBO, there were two reports of anaphylaxis. Monitor individuals for signs and symptoms of hypersensitivity reactions following vaccination with ERVEBO. Appropriate medical treatment and supervision must be available in case of an anaphylactic event following the administration of ERVEBO.
Limitations of Vaccine Effectiveness
Vaccination with ERVEBO may not protect all individuals. Vaccinated individuals should continue to adhere to infection control practices to prevent Zaire ebolavirus infection and transmission.
The safety and effectiveness of ERVEBO have not been assessed in immunocompromised individuals. The effectiveness of ERVEBO in immunocompromised individuals may be diminished. The risk of vaccination with ERVEBO, a live virus vaccine, in immunocompromised individuals should be weighed against the risk of disease due to Zaire ebolavirus.
Vaccine virus RNA has been detected by RT-PCR in blood, saliva, urine, and fluid from skin vesicles of vaccinated adults. Transmission of vaccine virus is a theoretical possibility.
The clinical development program for ERVEBO included clinical studies conducted in North America, Europe and Africa, in which a total of 15,399 adults received a dose of ERVEBO. The total number of subjects vaccinated with ERVEBO in double-blind, placebo-controlled trials was 1,712 and in open label trials was 13,687.
The most common injection-site adverse reactions reported by subjects taking ERVEBO in Study 1 (N=500) were injection-site pain (34.0%) and redness/swelling (2%). The most common injection-site adverse reactions reported by subjects taking ERVEBO in Study 2 (N=1051) were injection-site pain (70.0%), swelling (17%), and redness (12%).
The most common systemic adverse reactions reported following vaccination with ERVEBO in Study 1 (N=498) were headache (37%), feverishness (34%), muscle pain (33%), fatigue (19%), nausea (8%), joint pain/tenderness (7%), rash (4%), and abnormal sweating (3%). The most common systemic adverse reactions reported following vaccination with ERVEBO in Study 2 (N=1051) were joint pain (18%), arthritis (5%), rash (4%), and vesicular lesions (2%).
Arthralgia was reported to occur in 7% to 40% of vaccine recipients in blinded, placebo-controlled studies. Severe arthralgia, defined as preventing daily activity, was reported in up to 3% of subjects.
Arthritis (including events of arthritis, joint effusion, joint swelling, osteoarthritis, monoarthritis or polyarthritis) was reported to occur in 0% to 24% of subjects in blinded, placebo-controlled studies in which subjects received ERVEBO or a lower dose formulation, with all but one study reporting arthritis in <5% of subjects. Most occurrences of arthritis were reported within the first few weeks following vaccination, were of mild to moderate intensity, and resolved within several weeks after onset. In one study conducted in Switzerland (Study 5, NCT02287480), 102 subjects received ERVEBO or a lower dose formulation. In this study, arthritis was reported to occur in 24% of subjects and severe arthritis, defined as preventing daily activity, in 12% of subjects.
Rash was reported to occur after administration of ERVEBO in blinded, placebo-controlled studies, with all but one study reporting rash in <9% of subjects. In Study 5, rash was reported to occur in 25% (n=4) of ERVEBO recipients and 7.7% (n=1) of placebo recipients.
White blood cell counts were assessed in 697 subjects who received ERVEBO. Decreases in lymphocytes were reported in up to 85% of subjects and decreases in neutrophils were reported in up to 43% of subjects. No associated infections were reported.
Among 15,399 ERVEBO recipients, two serious adverse reactions of pyrexia were reported as vaccine-related. In addition, two serious adverse reactions of anaphylaxis were reported as vaccine-related. None of these serious adverse reactions were fatal.
Interference with Laboratory Tests
Following vaccination with ERVEBO, individuals may test positive for anti-Ebola glycoprotein (GP) antibody and/or Ebola GP nucleic acid or antigens. GP-based testing may have limited diagnostic value during the period of vaccine viremia, in the presence of vaccine-derived Ebola GP, and following antibody response to the vaccine.
USE IN SPECIFIC POPULATIONS
There are no adequate and well-controlled studies of ERVEBO in pregnant women, and human data available from clinical trials with ERVEBO are insufficient to establish the presence or absence of vaccine-associated risk during pregnancy.
The decision to vaccinate a woman who is pregnant should consider the woman’s risk of exposure to Zaire ebolavirus.
Human data are not available to assess the impact of ERVEBO on milk production, its presence in breast milk, or its effects on the breastfed child. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ERVEBO and any potential adverse effects on the breastfed child from ERVEBO or from the underlying maternal condition. For preventive vaccines, the underlying condition is susceptibility to disease prevented by the vaccine.
Clinical studies of ERVEBO did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger subjects.
More About the Development of the Vaccine
ERVEBO, known as V920 in its investigational phase, was initially engineered by scientists from the Public Health Agency of Canada’s National Microbiology Laboratory and the technology was subsequently licensed by a subsidiary of NewLink Genetics Corporation. In late 2014, when the Ebola outbreak in western Africa was at its peak, and with the goal of applying its capabilities in process research, clinical development, and manufacturing to an important global effort, Merck acquired the rights to develop V920 from NewLink Genetics. Since that time, the company has worked closely with a diverse range of external collaborators to enable a broad clinical development program with partial funding from the U.S. government, including the Department of Health and Human Service’s Biomedical Advanced Research Development Authority (BARDA) and the Department of Defense’s Defense Threat Reduction Program (DTRA) and Joint Vaccination Acquisition Program (JVAP). Beginning in 2015 Merck began manufacturing the emergency-use supplies that have been used to support outbreak response efforts prior to availability of licensed doses in collaboration with Gavi. Merck’s ongoing V920 vaccine supply replenishment activities are supported by partial Federal funding from BARDA under Contract No. HHSO100201700012C. Merck has been responsible for the research, development, manufacturing and regulatory efforts in support of V920. The company has committed to working closely with other stakeholders to accelerate the continued development, production and availability of the vaccine.
For more than 125 years, Merck, known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases in pursuit of our mission to save and improve lives. We demonstrate our commitment to patients and population health by increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to prevent and treat diseases that threaten people and animals – including cancer, infectious diseases such as HIV and Ebola, and emerging animal diseases -- as we aspire to be the premier research-intensive biopharmaceutical company in the world. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.
Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA
This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the “company”) includes “forward-looking statements” within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.
Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.
The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company’s 2018 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).
Before administering ERVEBO® (Ebola Zaire Vaccine, Live), please read the Prescribing Information at https://www.merck.com/product/usa/pi_circulars/e/ervebo/ervebo_pi.pdf . The Patient Information is also available at https://www.merck.com/product/usa/pi_circulars/e/ervebo/ervebo_ppi.pdf.
To read more Press Release articles, click here.