WHO-MSD Collaboration to Bring an Ebola Vaccine to the Populations in Need

Transcription

1 WHO-MSD Collaboration to Bring an Ebola Vaccine to the Populations in Need Jules Millogo, MD, MSc Director, Public Health Partnerships Merck & Co, Inc. North Wales, PA, USA

2 V920: rvsvδg-zebov-gp Vaccine V920 is a recombinant, replication-competent, vesicular stomatitis virus (VSV)-vectored-vaccine containing only the GP protein of Ebola virus (no live Ebola virus) VSV WT Glycoproteins switched VSVΔG/ZEBOV-GP The Zaire Ebola virus (ZEBOV) glycoprotein (GP) antigen is displayed in native conformation on the surface of VSV 2

3 The International Partnerships Facilitating V920 Clinical Trial Evaluation Study Sponsors and Sites N vaccinated with V920 Phase I Safety and Immunogenicity Trials Using Varying Vaccine Dose Levels U. Dalhousie Halifax, Canada 30 WRAIR Silver Spring, MD, USA 30 NIAID Bethesda, MD, USA 30 NewLink USA 422 WHO Geneva, Switzerland 100 WHO Hamburg, Germany 30 WHO Kilifi, Kenya trials (one conducted by MSD) ~18,000 total vaccinated for all doses combined (~17,000 subjects vaccinated at 2x10 7 dose) Efficacy was demonstrated in WHO s Ring Vaccination Trial WHO Lambarene, Gabon 115 adults/40 pediatric Phase II/III - Safety, Immunogenicity/Efficacy Trials at the Selected Vaccine Dose Level of 2x10 7 pfu WHO Guinea Ring Trial (Ebola ça Suffit) WHO/MSF Guinea FrontLine Workers CDC/COMAHS Sierra Leone (STRIVE) NIH/Liberian Partnership Liberia (PREVAIL I) MSD US / Canada / Europe (V ) ~5800 ~1800 ~8000 ~500 ~1060 3

4 V920 Overall Safety Conclusions to Date 4 Preliminary data in healthy, non-pregnant adults suggest an acceptable safety profile that in the context of demonstrated efficacy supports a positive benefit-risk ratio: V920 is generally well tolerated. Few vaccine-related SAEs reported to date Injection-site reactions very common; majority mild to moderate Common systemic AEs include headache, fatigue, myalgia, shivering/chills, subjective or objective fever, arthralgia, feeling unwell, nausea, influenza-like illness, and pain. Majority mild to moderate, short duration. Joint pain (arthralgia) has been seen in 5%-50% of participants, but joint swelling (arthritis) has been less common (<5% in most studies to 24% in one study). Majority of joint events were mild to moderate and resolved within several days (arthralgia) to weeks (arthritis); some subjects reported arthritis of prolonged duration, recurrence and/or sequelae for up to 2 years after vaccination, the longest duration of follow-up to date. Rash (with or without vesicles) and mouth ulcers have also been reported. Vaccine virus shedding is not frequent in adults and is more frequent in children; secondary transmission has not been demonstrated to date. Additional studies in children and HIV+ adults/adolescents have started but data from these studies are not yet available.

5 Summary of the V920 Product Profile (for Licensure) Description Proposed Indication Regimen Live, attenuated vesicular stomatitis (VSV) recombinant vaccine expressing Ebola Zaire surface glycoprotein Generic: Ebola Zaire vaccine (rvsvδg-zebov-gp, live attenuated) Prevention of Ebola-Zaire related disease Initial indication: Reactive use Eventual indication: General use prophylaxis Single dose Administration Intramuscular (IM) injection of 1mL Image Single-dose, liquid-frozen vial (1.2mL) Multi-dose available as pre-licensure emergency-use doses only Storage Target population 60 o C storage, could be kept up to two weeks at 2-8 o C after thawing. Shelf life 3 years; (5 years data TBD) Initial: 18 years of age (~2019) Eventual: 1 year of age (~2022) 5

6 Regulatory Strategy Objective: Obtain approval in African countries, facilitated by WHO Prequalification after approval by a stringent regulatory authority (e.g., EMA and/or U.S. FDA). Indication: Active immunization of at-risk subjects 18 years of age to protect against disease caused by Zaire ebolavirus. Four top priorities U.S. Food and Drug Administration (FDA) European Medicines Agency (EMA) World Health Organization Pre- Qualification Priority African countries (list being finalized) 6

7 Pre-licensure Deployment Mechanisms Expanded Access Clinical Protocols Designed to allow use in advance of product licensure under strict protocols requiring informed consent, adherence to GCP, collection of safety data, etc. Emergency Use Assessment and Listing (EUAL) Mechanism introduced by WHO to allow deployment of a vaccine outside of clinical trials prior to licensure in the context of Public Health Emergency of International Concern MSD filed an EUAL application for V920 with WHO in December 2015, with amendments submitted in ; application is currently under review and could be activated/approved if needed 7

8 The Way We Work With WHO PQ Team Regular and transparent Consultations, including ad hoc emergency meetings to address pressing issues Advance exchange of agenda and pending issues to address Leveraging each other s strengths- for instance WHO has frequent interactions with African NRAs Common voice when approaching regulatory agencies and associations: FDA, EMA, AVAREF 8

9 Pillars of the Collaboration Shared Priorities Mutual trust that both sides have the best intentions Mutual understanding of partner s constraints Willingness to adjust schedules in order to address priorities Defined roles and responsibilities and tacit commitment to implement agreed upon activities in allotted time 9

10 How WHO PQ Team Won MSD s Trust Technical Skills: WHO PQ Team has proven to be very knowledgeable in the regulatory area. Understanding of Manufacturing Environment: there is visible effort to understand Industry s compliance, legal and business environment. Willingness to Address Challenges- by adopting a common problem-solving attitude. 10

11 Illustrative Examples of Results of Collaboration Addressing programmatic suitability challenges (thermostability, label, etc.) Developing a strategy to facilitate African country registration Bringing on board AVAREF Liaison with countries 1 1

12 MSD-WHO Collaboration Challenges No clear demand size for Ebola vaccine Occasional lack of consistency of messages from WHO Continued need to overcome cultural barriers between Industry and WHO 12