Merck's Ebola Vaccine Will Get US FDA Decision Before March Review Deadline
Executive Summary
Staffer says agency will make a licensure decision "well ahead" of the March action date; 230,000 have received the vaccine under compassionate use.
The US Food and Drug Administration plans to complete review of Merck & Co. Inc.'s Ebola vaccine application before its March 14 user fee date.
Merck began a rolling submission of the biologics license application for the vaccine, V920 (rVSV∆G-ZEBOV-GP), in October 2018. The FDA accepted the application and granted it priority review in September.
At the 23 October meeting of the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices, an FDA staffer commented that the agency is "diligently working on completing our thorough review and arriving at a licensing decision well ahead of the March action date."
If licensed, V920 will be the first approved vaccine for Ebola. Merck announced on 18 October that the European Medicines Agency's Committee for Medicinal Products for Human Use had recommended a conditional marketing authorization for V920. If affirmed by the European Commission, the vaccine will be authorized under the brand name Ervebo and indicated for immunization of individuals 18 years of age and older.
CDC medical officer Mary Choi reported that in August 2018, the tenth and largest outbreak of Ebola virus disease was confirmed in the Democratic Republic of Congo and is ongoing. She said that as of 29 September, more than 3,000 cases and more than 2,000 deaths had been reported, and 165 healthcare workers had been infected.
Beth-Ann Griswold Coller, executive director of project leadership and management at Merck, presented safety and immunogenicity data on the vaccine to the committee. She said V920 is generally well tolerated in healthy, non-pregnant subjects 18 years of age and older and few vaccine-related serious adverse events have been reported to date. She said the majority of joint events reported were mild to moderate in intensity and resolved in days (arthralgia) to weeks (arthritis). However, she said a few subjects reported arthritis of prolonged duration and/or with recurrences/sequalae.
Merck seeks initial indication in adults 18 years of age and older in reactive use settings. Coller said supplementary indications will be based on immunobridging, inferring effectiveness in adults to use in children, HIV positive adults and adolescents. She noted that more than 230,000 people have received the vaccine under compassionate use.
Initial Focus Is On Narrow Population
Choi said ACIP will vote on policy options in February 2020 if the vaccine is licensed at that time.
Committee member Grace Lee, Stanford University School of Medicine, asked what the policy option might be.
Choi said the committee's priority is to make policy recommendations with respect to specific populations.
Nancy Messonnier, director of CDC's National Center for Immunization and Respiratory Diseases, replied that CDC feels urgency with regard to a narrower group than the proposed indication, that is, to those who work in healthcare facilities who may be asked to take care of patients and those traveling overseas to volunteer their services.
"There are a variety of practical implementation issues that need to be worked out before you make a recommendation, in terms of what the specific risks groups are, how it impacts family members, sexual partners, questions about how you access the vaccine," Messonnier said. "The recommendation won't be just yes or no. It's got to include all the rest of things that we normally pay attention to."
The rVSV-ZEBOV vaccine uses a genetically engineered version of vesicular stomatitis virus (VSV) to carry an Ebola virus gene insert. It was originally engineered by scientists from the Public Health Agency of Canada's National Microbiology Laboratory and licensed to a subsidiary of NewLink Genetics Corp. in late 2014. Merck subsequently licensed V920 from NewLink.
Merck has produced investigational doses of the vaccine for use in clinical trials and under emergency situations at its US plant and is working on a dedicated plant in Germany to supply the vaccine once it is licensed. (Also see "Merck's View On The Challenges Of Ebola Vaccination In The DRC" - Pink Sheet, 13 Nov, 2018.)
The World Health Organization is laying the groundwork to ensure that African countries at risk of an Ebola outbreak are able to approve the vaccine for use after it is authorized in the EU or the US. (Also see "WHO To Facilitate Rapid Roll Out Of Merck's Ebola Vaccine In Africa" - Pink Sheet, 28 May, 2019.)