1. Dr. André Tchouatieu MMV ACCESS department tchouatieua@mmv.org
MMV’s contribution to ACCESS-SMC
Dr. André Tchouatieu MMV ACCESS department

2. Outline What is MMV?? MMV into ACCESS SMC
Second SPAQ child friendly development
Next generation SMC drugs
SPAQ forecasting tool

3. Supports Partners to get: Works w/ Country Partners for:
ACCESS
Supports Partners to get:
SRA approval
WHO pre-qualification
Priority country registrations
ACCESS
Provides inputs to:
National guidelines
New financing options
Training & education
ACCESS
Works w/ Country Partners for:
Proper case management
Role of quality medicines
Correct drug use
PRODUCT
DEVELOPMENT
REGULATORY
APPROVAL
READINESS
POLICY &
FINANCING
DISTRIBUTION
& DELIVERY
PATIENT
UPTAKE
ACCESS
Helps Determine:
Priority needs
Formulation & dosage
Patient & provider preferences
ACCESS
Helps Shape:
Demand forecast
Packaging
Price negotiations
ACCESS
Seeks better:
Market intelligence
Innovations in drug delivery
Access and Product Management
fills the gaps throughout the entire product lifecycle.

4. Second child friendly SPAQ development (I)
S Kant group
Anuh Pharma Ltd
(API)
SKAGE Exports
S.K. Distributors
ESKAY Iodine
Sevantilal Kantilal & Co
S.K. Logistics
ESKAY Fine chemicals
S Kant healthcare Ltd
(FP)
Sulfadoxine API manufacturer
FPP manufacturer
SP / SPAQ
Background information

5. Second child friendly SPAQ development (II)
Sulfadoxine API
WHO prequalification of Anuh Pharma’s sulfadoxine
Collaboration agreement MMV and S Kant Healthcare
Anuh Pharma’s inspection from French regulatory authorities: critical findings
Suspension of sulfadoxine API prequalification
Suspension of all activities related to the collaboration agreement Q3 Q1 Q2 Q4
2015
2016
Mock inspection at Anuh pharma, commissioned by MMV
Joint re-inspection EDQM/WHO-PQ
2017
2018
Reinstatement of GMP certificate and WHO-PQ

6. Second child friendly SPAQ development (IV) Overall timelines
Authorization to S Kant to resume activities
Submission to WHO – PQ with 3 months stability data
Prod scale up batch
Submission of 6 months stability data to WHO – PQ
Pilot BE
Prod 3 exhibit batches
Pivotal BE
Exhibit batches stability Q2 Q3 Q4 Q1
2016
Revisit existing and potential manufacturers
2017
2018
Evaluation of existing and potential manufacturers
Development of another source of quality assured API

7. SP-AQ packaging field-testing
Development of user-friendly packaging prototypes including a carer leaflet & CHW job aid
Country: Senegal – 4 regions ( Kédougou, Tambacounda, Kolda et Sédhiou)
Target groups: health professionals, CHWs & Care givers
Sample size: 120
Timelines:
Ethical approval by end March 2017
Data collection & analysis April & May 2017
Report and packaging finalization June 2017

8. Next generation SMC medicines
Impact of current SMC implementation on desired attributes of the next generation SMC drugs Testing the next generation SMC drugs attributes
Survey
112 interviewees (individual and focus group)
Phones interviews & field visit to Burkina Faso and The Gambia

9. Next generation SMC medicines Key survey aims and objectives
Overall objective: identify preferred attributes for future seasonal malaria chemoprevention (SMC) products in Sub-Saharan Africa, to eventually replace SPAQ once resistance emerges, and potentially expand SMC into seasonal transmission areas where SPAQ is not therapeutically effective (primarily East and southern Africa).
Identify the potential of existing anti‐malarial drugs as an alternative to SPAQ taking into account the risk/benefit ratio A
Identify attributes for compounds for SMC in order to inform the development of next generation SMC drugs, through in-depth qualitative discussions with global and national KOLs, policy-makers, health workers and caregivers C
Cross-check SMC countries’ preferences with East and Southern Africa SMC eligible countries through discussions with NMCPs D
Assess implementers and users experience with current products for SMC, identifying drivers and limitations of SPAQ B

10. Next generation SMC medicines Key survey outcomes
In the MDA context, analysis shows four attributes are as critical for the development of new SMC products
Well-known, safe product (suitable for MDA)
Efficacy at least equal to SPAQ
Child friendly formulation
Frequency of administration (able to maintain current very effective door to door campaign)

11. Conclusions & Recommendations Other Main Findings
SMC acceptability is high among all stakeholders, including eligible countries not implementing it
Increased interest likely to translate into faster adoption if a new product becomes available
Drivers for SPAQ as SMC drug: efficacy, long half life, known safety, two different MoA, availability and affordability
Similar arguments are likely to be considered when evaluating the new proposed drugs
Increased willingness to use (repurposed) well known drugs rather than new compounds which may require country pilots
Repurposing and recombining current molecules may still be the fastest option to replace SPAQ
Even in current “non SMC countries”, door-to-door campaign format considered the most appropriate one for MDA
A different campaign format would have to ensure / demonstrate similar adherence levels (e.g. polio or measles like campaigns)
Injection generally considered more effective (by the general population)
If the frequency is low (e.g. one injection per season), consider developing an injectable rather than an oral

12. Next generation SMC medicines
Expert consultation on SMC and next generation chemoprevention meeting
London January, 2016

13. Objectives and outcomes
Refine MMV’s TPP for future chemoprevention treatment
Consider perspectives on existing medicines that may be re-purposed in the short or medium term to support development of chemoprevention medicines
Understand evidence required for normative policy change and regulatory pathways for chemoprevention medicines
Outcomes
New TPP for chemoprevention developed
Prioritization of a repurposing strategy for SMC drugs
Drug development strategy considering both treatment and chemoprevention for the same compound.

14. Global Portfolio of Antimalarial Medicines
Translational
Product development
Access
Human volunteers
Patient exploratory
Patient confirmatory
Regulatory review *
Preclinical
Post approval
GSK030
GlaxoSmithKline
DDD498
Merck KGaA
P218
(Biotec Thailand)
Artefenomel/
Ferroquine
Sanofi
Tafenoquine
GSK/MMV
GSK/US Army
Rectal artesunate
Cipla/Strides/WHO-TDR
Artemether-
lumefantrine
Various Manufactures 1 **
DSM421
Takeda
(UTSW/UW/
Monash)
PA92
(Drexel/UW/GNF)
SJ733
St Jude/Eisai
KAF156/
Lumefantrine
Novartis
Dihydroartemisinin piperaquine
Paediatric
Sigma-Tau/Pierre Fabre
Arterolane/
piperaquine
Sun Pharma
Artemether-
lumefantrine
Dispersible
Various Manufacturers 3 2
AN13762
(Anacor)
MMV253
Zydus Cadila
ACT
Actelion
Cipargamin
Novartis
Co-trimoxazole
ITM Antwerp
Artesunate
for Injection
Guilin 3 **
UCT943
UCT
JPC3210
Jacobus
CDRI 9778
Ipca
DSM265
Takeda
(UTSW/UW/
Monash)
Artemisinin
naphthoquine
Kunming Pharma Co
Dihydroartemisinin- piperaquine
Sigma-Tau /Pierre Fabre 4
NPC1161B
Mississippi
GSK607
GlaxoSmithKline
N-tert butyl Isoquine
LSTM/Liverpool/GSK
Fosmidomycin Piperaquine
Jomaa Pharma/GmbH
Artemether sub-lingual spray
MRC/Suda
Pyronaridine-
artesunate
Shin Poong 5
MK4815
Merck
Methylene Blue/AQ
Heidelberg
Pyronaridine-
artesunate granules
Shin Poong 5
SAR97276
Sanofi
Artesunate-
amodiaquine
Various Manufacturers 6
Artemisone
UHKST
Artesunate-
mefloquine
Cipla/DNDi/
Farmanguinhos
AQ13
Immtech
Sulfadoxine
pyrimethamine+
amodiaquine
Guilin 7
Sevuparin
Dilaforette
MMV048
(UCT)

15. A few basic requirements for SMC From Market survey and Advisory Board
Attributes for new chemoprevention compounds/drugs:
Fixed dose combination (ideally both drugs with comparable duration of activity)
Suitable for a door to door delivery
Long shelf life
Long half life
Tolerated as well as SPAQ
Acceptable safety profile
Preventive efficacy non-inferior to SPAQ
Causal activity not required
Should be different to drugs reserved for malaria treatment
Single dose treatment

16. Seasonal Malaria Chemoprevention with SP-AQ targets the Orange/ yellow: an amazing opportunity to save lives
RX / year
Under 5yo pop’n in Sahel SMC region: 24.8M
No Rx available yet
Under 5yo pop’n in eastern and southern SMC settings: 14.1M
"Estimating the potential public health impact of seasonal malaria chemoprevention in African children", Cairns et al, Nature Communications, 6-June-2012

17. Next generation SMC medicines
Next steps
Identification of antimalarial or other drugs with potential to be repurposed in SMC
Development of a draft concept note for testing these drugs for SMC
Discussion and validation of the concept note with the chemoprevention expert group
Funding strategy
Request for proposal to research groups
Upon funding availability

18. SMC forecasting tool (I)
Rationale of the tool
SMC time bond intervention >> need for medium term visibility on commodities needs >> for planning purposes (donors, manufacturers)
All SMC countries for long term view and scale up perspective
Source of data
Sharing Compiled data Data cleaning and validation
MMV
Broadreach
Uploading data and tool management
Sharing template for data collection
Data cleaning
12 Countries NMCPS

19. SMC forecasting tool (II)
SMC focal persons

20. SMC forecasting tool (III)
Sustainability
Adaptation of the tool incorporate other interventions commodities (IPTp, ACTs, RDTs, etc….)
Link with The Global Fund tool WAMBO ??
Post Access SMC perspective
Broadreach to accommodate the data and upload regular updates
Need for fees for yearly update and data collection
Securing maintenance budget through another project (“buying time” solution)
Urgent need to look for solutions for this tool not to die after the project(s)

21. In conclusion
A new dispersible formulation of SPAQ expected for 2018 (WHO – PQd)
A new sulfadoxine API prequalified by 2019
A sustainability plan for SMC forecasting tool by 2018
A clinical study plan for new SMC medicines (repurposed) expected by end 2017

22. Thank you