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

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

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.

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

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

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

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

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

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

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)

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

Next generation SMC medicines Expert consultation on SMC and next generation chemoprevention meeting London 13-14 January, 2016

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.

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-451840 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)

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

Seasonal Malaria Chemoprevention with SP-AQ targets the Orange/ yellow: an amazing opportunity to save lives 100 000 000 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

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

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

SMC forecasting tool (II) SMC focal persons

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)

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

Thank you