Ebola vaccine

Unassigned

New Medicines

Ebola virus infection - prevention

Information

Vaccine
Merck Sharp & Dohme (MSD)
Merck & Co (name used in US for MSD)

Development and Regulatory status

Pre-registration (Filed)
Pre-registration (Filed)
Pre-registration (Filed)

Apr 19: A NDA for an ebolavirus vaccine has been filed in EU, under accelerated assessment programme - am assuming it is this one [26].


Nov 18: Merck announced it has started the submission of a rolling Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for V920 (rVSV∆G-ZEBOV-GP, live attenuated), the company’s investigational vaccine for Ebola Zaire disease. Under an emergency use authorisation, health officials used the vaccine this year against outbreaks in the Democratic Republic of Congo. Although it hasn’t yet won international approvals, advisors for the World Health Organization have recommended its use to combat outbreaks when no licensed vaccines are available [24].


Nov 17: Merck & Co have announced that the anticipated filings for its Ebola vaccine by the end of 2017 have been delayed and it is now aiming for filing in 2018. The delay could jeopardise the $5 million advance purchase commitment from Gavi, the global vaccine alliance announced Jan 16 which was contingent on Merck filing for approval by the end of 2017 [21].


Oct 17: BARDA will provide $39.2 million for late stage development and purchase of Merck´s Ebola vaccine using funding from Project BioShield which supports late-stage development toward licensing of Ebola vaccines and drugs, and stockpile for potential use in a public health emergency [19].


Oct 16: Merck and NewLink Genetics receive a $24.8 million contract to support development of their Ebola vaccine. The new grant brings the total invested into rVSV∆G-ZEBOV GP (V920), by the Biomedical Advanced Research and Development Authority (BARDA) of the U.S. Department of Health and Human Services to more than $100 million. The award also includes another optional $51 million. The funding will go to manufacturing facility readiness, manufacturing process qualification activities and clinical trials [14].


Jul 16: FDA grants Breakthrough therapy designation [13].


Jul 16: EMA grants PRIME status [13].


Jan 16: Merck plans to submit rVSV-ZEBOV vaccine for regulatory approval by end of 2017. Merck has won $5 million from Gavi, the global vaccine alliance, for costs due to late-stage trials, licensure and prequalification by the WHO. Merck has filed an emergency use application with the WHO. If approved, the vaccine will be available for use if there is another outbreak before it is licensed. The company will provide 300,000 doses starting in May this year for use in clinical trials or emergency situations [12].


Oct 15: PIII development is underway [11].


Jul 15: rVSV-ZEBOV, was found to have 100% efficacy (95% confidence interval: 74.7 - 100%; p=0.0036) and protected against Ebola virus infection within 6 to 10 days of vaccination in an interim analysis of the PIII ring vaccination trial in Guinea. Preliminary conclusions from this study, were published on-line today in The Lancet. [9]


Mar 15: PIII in Guinea [7].


NewLink developed the vaccine and started trials in Canada and the U.S. before teaming up with Merck in an exclusive licensing agreement to research, develop, manufacture and distribute NewLink´s candidate [6].


Jan 15: PII trial resumes with a lower dose of 300,000 vaccine particles per dose vs. the original dose of up to 50 million vaccine particles [6].


Dec 14: Temporary halt on PII clinical trial at Geneva University Hospital (Switzerland) after 4 of 59 pts complained of joint pain in their hands and feet. The manufacturer states that this is “a well-documented phenomenon which does not worry specialists. The temporary interruption of a clinical trial is a standard precautionary measure in such cases.” Trials are expected to continue In Jan 2015 in 15 more volunteers once additional tests are completed to confirm that the pain was benign and temporary. US NIH plans to begin a randomised, controlled Phase III trial in 2015 [5]


Oct 14: WHO announces it plans to start testing VSV-EBOV in west Africa in Jan 2015. Trials in healthy volunteers are underway in the US, and are expected to start in Switzerland, Germany, Gabon & Kenya shortly [4].


Oct 14: The Government of Canada announces start of clinical trials at the Walter Reed Army Institute of Research in the US. Results expected Dec 14 [2].


Oct 14: PI [1].


Category

Vaccine based on the animal vesicular stomatitis virus (VSV) combined with a portion of the protein covering of the Ebola virus. developed by researchers at the Public Health Agency of Canada’s National Microbiology Laboratory.
Ebola virus is highly infectious and leads to a potentially fatal disease with fever, malaise, vomiting, mucosal and gastrointestinal bleeding, oedema, and hypotension. Mortality is 50-90% [3].
Ebola virus infection - prevention
Intramuscular

Trial or other data

Jan 19: Merck is to ship another approximately 120,000 doses of their Ebola vaccine to Congo by the end of next month amid the world´s second-deadliest outbreak. >63,000 people have already received the vaccine in the outbreak that was declared Aug 2018 [25]


May 18: With reports of an outbreak in the Democratic Republic of Congo, the WHO is working with other organisations and officials to conduct ring vaccination using the rVSV-ZEBOV vaccine. Because the vaccine hasn´t yet won regulatory approval, an importation licence must be obtained as well as formal agreement on research protocols [23].


Apr 18: A new study, published in Lancet Infectious Diseases, shows antibodies persist for two years after a single dose of rVSV-ZEBOV vaccine. Researchers examined participants from a previous PI study who returned for follow-up. All 44 of those patients who had received a high dose of the vaccine remained seropositive at two years, and 33 of 37 who got a lower dose were still seropositive [22].


Oct 17: A US-Liberia research team have now published results showing Ebola vaccines from GSK and Merck elicited antibody responses that lasted one year after vaccination. For the PII study, sponsored by the National Institute for Allergy and Infectious Diseases (NIAID), participants received GSK´s vaccine (n=500), Merck´s vaccine (n=500) or placebo (n=500). At one week, researchers documented "modest" responses that ended up growing significantly so that, after a month 71% of recipients of the GSK vaccine developed an antibody response, vs. 84% of those who received Merck´s vaccine and 3% for placebo. Antibody responses stayed strong to the one-year point: 64% for GSK´s vaccine, 80% for Merck´s and 7% for placebo. Findings have been published in the NEJM [20].


May 17: Shortly after a WHO advisory committee recommended last month that Merck’s vaccine be deployed in the event of an outbreak, rVSV-ZEBOV-GP vaccine could be used to combat a new outbreak in the Democratic Republic of the Congo. The current outbreak involves the Zaire strain of Ebola, which Merck’s candidate targets [18].


Apr 17: The World Health Organization has recommended Merck´s rVSV-ZEBOV-GP vaccine be used in the event of an outbreak as it is the only candidate currently to demonstrate clinical efficacy and effectiveness in PIII trials. However if the emerging outbreak is caused by an Ebola virus species other than Zaire, consideration should be given to the use of other candidate vaccines that target the putative viral species. Ring vaccination, as used in the PIII study in Guinea, is the recommended delivery strategy [18].


Aug 15: Merck initiated a phase III trial to evaluate the safety and immunogenicity of three consistency lots and a high dose lot of rVSV-ZEBOV-GP in healthy adults (NCT02503202; EudraCT2015-001658-14). The primary endpoint is Geometric Mean Titer of anti-ZEBOV glycoprotein antibody. The randomised, double-blind trial is designed to enrol approximately 1125 subjects in the US and Spain [17].


Jan 16: The National Institute of Allergy and Infectious Diseases (NIAID) initiated a phase III study to evaluate the immunogenicity of rVSV-ZEBOV-GP, in subjects at potential occupational risk for Ebola virus infections (NCT02788227). Approximately 300 subjects will be enrolled in the US [17].


Jan 17: Final results of 2 (NCT02269423 and NCT02280408) PI trials (n=78) published in NEJM. Results show vaccine candidate elicited anti-Ebola antibody responses and support further evaluation of 20 million PFU dose for preexposure prophylaxis and of a 2nd dose to boost antibody responses [16].


Dec 16: Final results from PIII Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!) published in The Lancet. Interim assessment of data from this study (n=4160 vaccinated in Guinea) suggests that rVSV-ZEBOV offers substantial protection against Ebola virus disease, with no cases among vaccinated individuals from day 10 after vaccination in both randomised and non-randomised clusters [15].


Aug 15: Merck and NewLink’s Ebola vaccine rVSV-ZEBOV shows 100% effectiveness in a trial in Guinea. The study used a ‘ring design’. Rather than use a placebo group, these trials found people who had been in contact with someone with Ebola and vaccinated half of them immediately, and the other half three weeks later. In the groups that were vaccinated immediately, there were no cases of Ebola from 10 days after vaccination – the time allowed for the immunity to develop. In the delayed-vaccination group, there were 16 cases, a statistically significant difference. Børge Brende, the foreign minister of Norway, which helped fund the trial, said rVSV-ZEBOV may be a silver bullet against Ebola, helping to bring the current outbreak to zero and to control future outbreaks [10].


Apr 15: Merck & Co and NewLink Genetics confirm that the third, late-stage, clinical trial of rVSV-ZEBOV-GP (V920) has begun in Sierra Leone. The PII/III safety and effectiveness STRIVE trial will involve 6,000 health and other frontline workers, and is being led by the Sierra Leone College of Medicine and Allied Health Sciences, Sierra Leone Ministry of Health and Sanitation, and the US Centres for Disease Control and Prevention [8].


Mar 15: PIII study starts in Guinea. Vaccination will take place in areas of Basse Guinée, which has the highest number of cases in the country, and the strategy adopted will be “ring vaccination”, which involves identifying a newly diagnosed case of Ebola – the ‘index case’ – and then tracing of the patient’s contacts, who are then vaccinated. The dual objectives of the trial are to assess if VSV-EBOV protects the contacts who were vaccinated and if this will successfully create a buffer around the index case to prevent further spread of infection [7].


Aug 14: The Government of Canada announced it will be shipping 800 vials of its experimental Ebola vaccine to the WHO, so that the vaccine can be made available as an international resource. The WHO, in consultation with partners, including the health authorities from the affected countries, will guide and facilitate how the vaccine should be distributed and used. The remaining vials of the vaccine will be kept in Canada for further research and compassionate use as required [2].