Status of COVID-19 vaccines: perspectives for West Africa

24th of November, 2020

Dr Olivier Manigart, GFA Consulting Group, PROALAB Senior Team Leader, WAHO Pharm Mrs Sybil Ossei - Agyeman- Yeboah, Pharmaceutical and Quality Assurance Analyst Professional Officer: Pharmaceuticals, WAHO

www.wahooas.org; @OoasWaho Outline

• Current status of vaccine development; • Country orders for vaccines under development; • COVID-19 epidemiological situation in ECOWAS; • Proposed Regional Strategies to make vaccines available in West Africa.

• Conclusion.

www.wahooas.org; @OoasWaho 2 Roads investigated for immunization (2) • Active immunization against SARS-CoV-2: Licensure:

• Protein Subunit Vaccine (FBRI SRC VB VECTOR, Rospotrebnadzor, Koltsovo)

• Sputnik V (Gamaleya Research Institute)

Emergency/Limited Use:

• Ad5-nCoV (Tianjin CanSino Beijing Institute of Biotechnology)

• BBIBP-CorV (CNBG Beijing)

• Inactivated Vaccine (CNBG Wuhan)

• CoronoVac (Sinovac)

Che Y, Liu X, Pu Y, et al. Randomized, double-blinded and placebo-controlled phase II trial of an inactivated SARS-CoV-2 vaccine in healthy adults. Clin Infect Dis, 09Nov20 www.wahooas.org; @OoasWaho 4 Roads investigated for immunization (3)

Last developments for three most advanced vaccines from Western with preliminary efficacy results:

BNT162b1 (Pfizer, BioNTech) • Nucleoside-modified RNAs, formulated in lipid nanoparticles • BNT162b1 encodes an optimized SARS-CoV-2 receptor-binding domain (RBD) antigen (while BNT162b2 encodes an optimized SARS-CoV-2 full-length spike protein antigen).

• COVID-19 vaccine BNT162b1 elicits human antibody and T H 1 T cell responses • The robust RBD-specific antibody, T cell and favourable cytokine responses induced by the BNT162b1 mRNA vaccine suggest that it has the potential to protect against COVID-19 through multiple beneficial mechanisms. • BNT162b2 may have an efficacy of over 90% in preventing infection within seven days of the second dose mRNA-1273 (Moderna) • RNAm based, Spike protein, administered through intra-muscular route as lipid-nanoparticle • Moderna COVID-19 Vaccine mRNA-1273 Reports 94.5% Efficacy in Early Data. November 16, 2020

ADZ1222 (AstraZeneca/Oxford) • Results at D28 showed neutralizing Ab in more than 90% of the volunteers. • Fridge stable. Easy to transport. Cheaper (about £3 instead of £20 for others). • Efficacy of 70.4% and surprisingly 90% if a lower dose is used for the first dose.

Nature. 2020 Oct;586(7830):594-599. doi: 10.1038/s41586-020-2814-7 www.wahooas.org; @OoasWaho 5 COVID-19 Vaccine Development: 16Nov20

Source: https://pharmanews.linksbridge.com/Covid-19

www.wahooas.org; @OoasWaho 6 Status of COVID-19 phase III development as of 01Nov20 Candidate Characteristics of Vaccines Lead Developers Status Information /Mar, 2020 Update 01 Nov20

BNT162b1 mRNA encapsulated in lipid BioNTech, Fosun & Pfizer Phase 3 Sept 2020, Dec 2020 (100M doses), Dec USA, Brazil, SA, India of nanoparticles USA 2021 (1,3 B doses), the 30,000 people

mRNA-1273 mRNA encapsulated in lipid Moderna Inc USA Phase 3 in Sept 2020, Completion Date: June 1, Trial started in the USA nanoparticles 2021, 100M doses-USA 30,000 people

AZD1222 Adenovirus + Spike AstraZeneca & University Phase 3 on 4 Sept, July 2021 product completion USA, Brazil, SA, Britain, glycoprotein(S) of Oxford 2020 400-million-dose EU India-half of the 30,000 400-million-dose JJ people

INO-4800 DNA plasmid coding for Inovio Pharma USA Phase 3 in Nov, 2020 April, 2020 Inovia/GSK protein S Phase 3 Collaborate Ad26.COV2.S Recombinant vaccine Janssen's Covid-19 Phase 3 23 Sept 2020 60,000 volunteers globally

CTII-nCoV Adenovirus type 5 vector- CanSino Biologicals China Phase 3 Sept 2020 Completion Date: Saudi Arabia, Russia, protein S Approved by Chinese December 2022 Brazil, Chile (Ad5-nCoV) Military Approved by Chinese Military Sputnik V (Gam-COVID- Recombinant vaccine Military & Gamaleya Phase 2 2,500 out of Phase 1- 18 June 2020, Phase Supply deal Brazil and Vac Lyo) Ad5/26 Sputnik Vaccines Research Center, Russia 40,000 volunteers for 2- 23 June, 2020 Mexico but scientifically phase 3 Phase 3 in Mid August, 2020, questioned

• NVX-CoV2373 (Novavax) USA; COVAXIN inactivated virus India; recombinant protein subunit adjuvanted RBD China. www.wahooas.org; @OoasWaho 7 Global Requirements and Gaps for COVID-19 Vaccines

• The COVID-19 Pandemic has created panic and raised the highest demand for effective vaccines; • Speed of Development is important, but without compromising scientific efficacy, quality, safety and immunogenicity; • 5.7 billion doses under development pre-ordered. Global population = 7.8 billion x 2 doses =15.6 billion doses. How then do we promote fair and equitable access worldwide?

No Companies Quantity of Vaccines Countries Orders/COVAX Demand available by Dec 2021

1. AstraZeneca & University of Oxford 1.9 billion doses, Germany, France, Italy and the Netherlands. 400 million doses, USA 400 million doses UK 100 million doses LMICs 1 billion doses, 2. BioNTech & Pfizer USA 1.3 billion doses USA 600million doses UK 30 million doses 3. Moderna Inc USA 500 million-1billion doses USA 300 million doses 4. CanSino Biologicals China 1.6 billion doses Chinese 1.6 billion doses 5. Inovio Pharma USA 1 million doses CEPI/COVAX 1 million doses 6. Military & Gamaleya Research Center, 70 million doses Russia 70 million doses Russia 7. Janssen/BARDA 1 billion doses Global supply 1billion doses 8. GSK/Sanofi 160 million doses Britain and USA 160 million doses CEPI/GAVI-COVAX-AMC/WHO (78 upper- and upper-middle- 5.4 billion vaccine doses income countries, 92 LMICs eligible ) Total 9.1billion doses Extra doses required globally = 6.5 billion doses 11.061 billion doses www.wahooas.org; @OoasWaho 8 CEPI/GAVI-AMC-COVAX/WHO Support for COVID-19 Vaccines by Dec 2021

• HIC: 40 EOIs, 0.5+ B people • UMIC: 38 EOIs, 1.0+ B people • LIC/LMIC: 92 AMC-eligible economies, 3.9 B people (AMC-eligible economies- agreed by the Gavi Board during the 30th July, 2020 meeting) COVAX Facility Dose Allocation projections Doses 950M 950M 100M = 2B Procured through Facility by HICs AMC doses for LICs and LMICs Buffer for emergency deployment Doses secured by end 2021 and UMICs (AMC 92) Goal • Protect public health and minimize societal and economic impact by reducing COVID-19 mortality • Equal allocation between LICs, LMICs and UMICs, HICs as we seek to reach 20% of the population* Timing LICs, LMICs receive doses at Timing is based on country need the same time as UMICs and HICs** vulnerability and COVID-19 threat

Priorities 1. Health and social care workers 2. High-risk adults 3. Further priority groups

**In alignment with WHO Allocation Framework **Rollout of doses subject to availability of funds https://www.gavi.org/vaccineswork/covax-explained www.wahooas.org; @OoasWaho 9 WHO SAGE Roadmap For Prioritizing Uses Of COVID-19 Vaccines In The Context Of Limited Supply

https://www.who.int/publications/m/item/who-sage-roadmap-for-prioritizing-uses-of-covid-19-vaccines-in-the-context-of-limited-supply www.wahooas.org; @OoasWaho 10 Covid-19 SitREP, ECOWAS, November 22th, 2020.

Infected cases = 201,614 Deaths =2,842 (1.41%) Recovery=189,917 (94.2%)

✓ Week (37): the daily average of new confirmed cases was 532.

✓ Week (38): the current daily average of new confirmed cases is 489. www.wahooas.org; @OoasWaho 11 Access to COVID-19 Vaccines in West Africa

West Africa with a population of 365Million - has two pathways Lesson learnt-Collaboration – PPP: 15 MS are Additional Brazilian government in collaboration with the Oswaldo Cruz eligible to the access via Local Foundation (Fiocruz) signed an agreement with COVAX initiative Production AstraZeneca for 30.4m doses and transfer of technology;

Receive the active pharmaceutical ingredient (API) from AstraZeneca and including the phases of formulation, bottling, labelling, packaging, and quality control.

West Africa Governments would have to pool funds to access the COVAX vaccines, but quantities may not be enough

Local production of COVID-19 vaccines would ensure access, sustainability, jobs creation and potential for other vaccines in future epidemics Leverage on existing local capacity

www.wahooas.org; @OoasWaho 12 Current Vaccine Development/Manufacturing Capabilities in ECOWAS (1)

• Innovative Biotech in Nigeria o Successfully introduced Typhoid Conjugate Vaccine and Rotavirus vaccine into the private and public markets in Nigeria, with a plan to backward integrate the capacities to manufacture these vaccines through tech transfer from Bharat Biotech, India. o Developed 3 VLP-based candidate vaccines and currently working with Merck, Germany to set up a VLP vaccine manufacturing platform facility in Nigeria. This will enable not only address the current Covid-19 vaccine needs of our continent, but to be ready to support future vaccine needs much quicker and offer pandemic readiness. o Working collaboratively with Medigen USA to develop and manufacture VLP-based Covid-19 candidate vaccine. • Pharmanova LTD in Ghana o Currently, we are importing Anti – Snake Serum and Anti- Rabies Vaccines for distribution in the country. o Putting up structures for the local Bulk Filling of Anti- Snake serum, Anti – Rabies vaccine, Anti- Tetanus vaccine, Anti- Gangrene, Anti- Diphtheria, Anti- Scorpion in collaboration with Vins BioProducts Ltd, India.

www.wahooas.org; @OoasWaho 13 Current Vaccine Development/Manufacturing Capabilities in ECOWAS (2)

• Biovaccines LTD in Nigeria o Plans are underway to set-up a vaccine facility under PPP arrangement with the federal government of Nigeria.

• Institut Pasteur Dakar in Senegal o Has end-to-end manufacturing capability of YF vaccine which is WHO Pre-Qualified – supplying both local and export markets. o Currently building a new large-scale facility which will be operational in 2023.

www.wahooas.org; @OoasWaho 14 Conclusion (1)

The risk is that (inter)national manufacturers whose COVID-19 vaccines are not approved for use in their countries would possibly ship substandard and falsified vaccines to low & middle income countries if caution is not taken

• The 21st Assembly of ECOWAS Health Ministers on 4th of August 2020 adopted a resolution on “Access to COVID-19 Vaccines for West Africa and West Africa therefore needs to: Acceleration of Local Production”; • Take immediate action to pool financial resources to compete in buying approved th • The 57 Ordinary Session of the ECOWAS Authority COVID-19 vaccines instead of waiting for free of Heads of States and Government on 7th of September 2020 resolved that strategies for making donations from partners or donors; COVID -19 vaccine in the region should be explored and • Support vaccines producing industries in the • WAHO has prepared a concept paper to create a region through Public-Private-Partnership (PPP) task force of technical experts, local manufacturers, initiatives for medium to long term sustainability member states and financial partners to develop of vaccine acquisition in the region. strategies and explore opportunities for making COVID -19 vaccines available to our population www.wahooas.org; @OoasWaho 15 Conclusion (2)

• < 1% of vaccines produced in Africa • Very few proportion of vaccines and medicines evaluated in Africa • Some centers already demonstrated efficiency (NHRC, KHRC, Nanoro, Nouna HDSS, MRC The Gambia, CVD Mali, etc.) in evaluating vaccines • Need of Quality Laboratories and networks to increase these numbers (PROALAB, REDISSE, RESAOLAB, RESOLVE, etc.) • Need of sustainable “Health Demographic Surveillance Systems (HDSS)” • Many HDSS already existing in West Africa • Advocacy for vaccine evaluation in the ECOWAS region • African Vaccine Manufacturing Initiative (AVMI) • Keep ONE HEALTH in the loop since many centers are/were producing animal vaccines • Need of CAB to involve populations • Two sub-groups in the COVID-19 Accessibility Task Force: Production & Access and demand currently working

www.wahooas.org; @OoasWaho 16 Thank you

Merci Obrigado

365 Million Population www.wahooas.org; @OoasWaho 17 Back-up Slides

365 Million Population www.wahooas.org; @OoasWaho 18 Many unanswered questions

• Will a single dose be sufficient in older adults, or is a booster dose required? • Does longevity of response or rates of waning differ with a two-dose regimen? • Does longevity of clinical protection require cell-mediated responses? • Are there host-specific differences in immunogenicity by age, sex, or ethnicity? • Do T-cell responses correlate with protection irrespective of humoral titres? • Are there specific adverse events in pregnant women? Bar-Zeev, Lancet, 2020

After the beginning of mass-vaccination, more questions will arise: • How will risk group fare (e.g. elderly people with hypertension, diabetes, obesity, etc.)? • Are re-vaccinations needed at regular intervals? • Will SARS-CoV-2 mutate so that the vaccines will have to be adapted like the annual flu vaccines?

• What is the importance of non-specific immunity, innate immunity and how can this be triggered?

www.wahooas.org; @OoasWaho 19 Caution with Ad5 as a vector

HIV Step and Phambili vaccine trials (2008):

• Pre-existing Ad5 immunity might dampen desired vaccine- induced responses. • Ad5 immune complexes activate the dendritic cell–T cell axis, which might enhance HIV-1 replication in CD4 T cells. • Ad5-specific CD4 T cells could have an increased susceptibility to HIV infection. • In a non-human primate challenge study, infecting rhesus macaques with Ad5 and then immunising them with a replication-incompetent SIV vaccine based on Ad5 increased risk of SIV acquisition from low-dose SIV penile challenge. • Subclinical inflammation and alterations to epithelial barriers at the inner foreskin of CCR5-positive CD4 T cells could contribute to high rates of sexually transmitted infections, including HIV, in uncircumcised men

www.wahooas.org; @OoasWaho 20 Scope of Work and Costs

Production of new Master Cell Bank (Virus Like Particles-VLP), Grand Total= 626.86M$ Baculovirus, Clinical Phase I, ll, • 2.86M$ To be paid over 2 years & lll Materials

Labels coded for traceability through the supply chain and distribution to prevent falsified Build end-to-end vaccine, CAPEX & OPEX • 64M$ products circulating in the region

Manufacture 800 million doses (assuming 2 doses/person, for • 560M$ CAPEX-Capital Expenditure population of aprox. 400M in ECOWAS OPEX- Operational Expenditure www.wahooas.org; @OoasWaho 21 Roadmap of the feasibility study for establishing vaccine R&D and manufacturing capacity for West Africa Subregion (October 2020 – February 2021) Scope of Work Deliverable Timelines Responsible Budget

Assessment and evaluation of current Covid-19 vaccine and other vaccines Capacity assessment and landscape July -October 2020 manufacturing capacity in the subregion conducted. analysis report

Development of a detailed capacity strengthening strategy and work plan November – Capacity strengthening workplan based on the outcome of the capacity assessment December 2020

A list of short, Medium and Long- Facilitate partnerships between potential subregional vaccine term interventions for building local manufacturers and organizations currently involved in COVID-19 vaccine vaccine manufacturing capacity research and development facilitated. developed.

A high-level meeting on vaccines Advocate for increased investment in developing the vaccine R & D and manufacturing in the subregion manufacturing capacity in West Africa executed.

A pragmatic vaccine policy for the Work with relevant stakeholders to refine a vaccine policy for the subregion. subregion developed.

Roadmap for establishing the Establishing a vaccine and biologicals Fund for Africa Vaccines Trust Fund for the subregion developed.

www.wahooas.org; @OoasWaho 22