R&D for potential vaccines for the Ebola virus

Transcription

1 R&D for potential vaccines for the Ebola virus Update 4 March 2015 Roberto Bertollini MD MPH Chief Scientist and WHO Representative to the EU

2 Gathering knowledge Since August 2014, series of consultations with key international experts and stakeholders to identify potential therapeutic or preventive solutions for Ebola Based on concerted expert advice, WHO has prioritized a number of products for further investigation through human testing: - three candidate vaccines - a shortlist of antiviral drugs - convalescent whole blood and plasma - rapid point-of-care diagnostics

3 Two lead candidate vaccines A- rvsv-zebov recombinant vesicular stomatitis virus (Merck) The rvsv vaccine aims to induce EVD-specific immune responses. NewLink Pharmaceuticals/Public Health Agency of Canada B - ChAd3-ZEBOV chimpanzee adenovirus 3 (GSK) Uses a chimpanzee adenovirus that does not grow, containing the gene for EVD surface protein. GSK/NIAID Kanapathipillai R et al. N Engl J Med DOI: /NEJMp Candidate vaccines were selected on the basis of protection in nonhuman primates post-lethal challenge (100%) and availability of GMP-grade vaccine.

4 Johnson & Johnson Phase 1 trials Ad26/MVA based approach with 100% NHP efficacy after the booster dose First Phase 1 trial started in January 2015 in UK Phase 1 clinical trials planned for USA and Africa soon Major commitments from company for accelerated development and scaled-up manufacturing, with Phase 2-3 planned for 2015

5 Clinical trials phases Phase I trials involve 20 to a few hundred healthy individuals and examine safety and immune response. They also identify commonly-occurring adverse reactions. Phase II trials involve several hundred to a few thousand people and determine the optimum vaccine composition for achieving protection while ensuring safety. Phase III trials involve thousands to tens of thousands of people and examine the vaccine's ability to prevent a disease as intended. They also provide further safety information. Post-licensure monitoring or formal Phase IV trials involve the target population. These surveillance activities identify, through spontaneous reporting systems to health authorities, less common adverse events, events which could occur after a long time, or events that may occur in specific subgroups of the target population. #

6 Vaccines Phase I studies Phase I clinical trials of the GSK vaccine in healthy adults completed in the United Kingdom, United States, Mali and Switzerland Phase I Merck vaccine trials near completion in Canada, the United States, Gabon, Germany, and Switzerland. Trials in Kenya began in December All trials under the auspices of national research institutions and oversight of the national regulatory authorities in the countries where they are taking place.

7 Safety summary from Phase 1 studies #

8 Vaccines Phase II and III studies Phase II clinical trials of the GSK vaccine are expected to begin in Cameroon, Ghana, Mali, Nigeria and Senegal in early 2015 Accelerated ethical and regulatory approval of trials facilitated by WHO through joint ethical and regulatory reviews of the trial protocols Phase III clinical trials are planned to start in the first quarter of 2015 in Guinea, Liberia and Sierra Leone to assess the extent to which the vaccines protect against EVD and to gauge the feasibility of full deployment Two other vaccines one by Johnson & Johnson, the other by Novavax are being developed and the J&J one has started trials in the UK

9 Phase III efficacy trial designs Liberia: Randomized controlled 3-arm trial in the community (Government and US NIH) Sierra Leone: modified Stepped-wedge trial with health care workers (Government and US CDC) Guinea: 2 protocols: Ring vaccination trial and immunization of frontline workers (Government, WHO, MSF)

10 Challenges for the Present and Future Overall declining disease incidence and/or change in geographical distribution in the three affected countries implications for current and planned clinical trials Case fatality rate changes/obfuscates baseline for judging efficacy of therapeutic interventions

11 Availability and funding Access to proven products for affected populations today and in the future is among WHO s primary concerns WHO, UNICEF and US CDC are partnering with countries on preparedness plans for large-scale introduction For vaccines, manufacturers of the two most advanced candidates have assured that ample supplies will be available for phase II and III testing, with production capacity for over a million doses of each candidate by year end Funding is in place for up to 30 million $ through the Vaccine Alliance (GAVI), whose Executive Board approved a US$300 million funding envelope in December 2014.

12 Next steps Strong emphasis must be placed on effectively engaging with communities to build trust and allay concerns about trials and vaccination campaigns. Regulatory authorities have committed to continued efforts to accelerate approval pathways without compromising safety and quality Changing epidemiological situation in the three affected countries means we will need to move faster in the evaluation of all products, in particular the vaccines WHO supports fast-tracking of vaccine phase III trial in Guinea to determine vaccine efficacy for this and future outbreaks

13 Thank you for your attention