Transforming the malaria landscape in the Sahel: seasonal malaria chemoprevention Diego Moroso, Malaria Consortium February 13, 2017

ACCESS-SMC is a UNITAID funded project led by Malaria Consortium in partnership with Catholic Relief Services, which aims at scaling up SMC in the Sahel. The project is supported by LSHTM, MSH, MMV and Speak up Africa, and it’s implemented in collaboration with the Ministries of Health in Burkina Faso, Chad, Guinea, Mali, Niger, Nigeria and the Gambia. During its life it will have provided approximately 45 million treatments to about 7 million children in these seven Sahelian countries.

Strategic intent Shape the market Demonstrate feasibility, safety and effectiveness at scale The project is fairly large, and has many objectives and complex deliverables, but we can probably summarize its strategic intent in two parts: One is Shaping the market. There were two core issues with the market. First, confirmed funded demand was to low and unreliable to allow manufacturers to seriously invest on and plan for expanded production of SMC drugs, so one objective of the project was to provide this funded certainty: a confirmed, funded demand for SP+AQ over a few years in order to encourage increased supply in the medium term. Second, the existing formulation of the drugs was not adequate for children: they’re hard pills, difficult to crush, they need significant amounts of water to be mixed with expensive sugar, which can hardly mask the extremely bitter taste. This had consequences both in terms of ease of administration and on rejection by beneficiaries. Thus the project wanted to use its funded demand as leverage in order to encourage the development of child-friendly, dispersible formulations. Assess the feasibility, safety and effectiveness of SMC at scale. Feasibility is key, as the intervention is no small feat. It implies shipping millions of treatments from (currently) the eastern-most tip of China to each country, for instance Burkina Faso, and in advance of the rainy season, so timing of orders and production is essential.

ACCESS-SMC: Goals and Achievements So what can we say about the achievements supporting these goals?

Shaping the market SP+AQ procurement, delivery and administration Let’s start with market shaping. Obviously one of the key objectives of the project is to timely procure, deliver and administer SMC drugs. Malaria Consortium, in agreement with the UNITAID, had to decide how many treatments were deemed enough to create that market push, and we came to the conclusion that 30M was a sufficient figure. Unfortunately, some of the issues mentioned above about supply-side constraints, materialized in 2014 in a perfect storm that resulted in both active pharmaceutical ingredients for SP and AQ to be unavailable beyond certain limited quantities. In fact, only 16.8 million treatments could be produced in time for the 2015 season, and ACCESS-SMC procured 14.7 million of them for the countries shown here. Last year, we managed to procure and deliver 30M treatments, and we tried to shift as much as possible to dispersible formulation. Approx. 80% of SMC drugs purchased by ACCESS-SMC in 2016 were in child-friendly formulation. 2015: 14.7M treatments 2016: 30M treatments

Shaping the market SMC market comparison, 2015 vs 2016 So, when we look at the market, how it’s moving, we can see a remarkable difference since 2015 both in terms of pledged funding for SMC drugs (worth around 45M in 2015, and estimated at over 70M treatments in 2016), and in terms production (now only capped by capacity… we moved from under 20M treatments to slightly more than 67M). As a comparison, we estimate that less than 5M treatments were procured in 2014 for actual implementation (that is outside research projects). As we can see there’s still an issue with capacity gap, as not everybody who was willing to buy this year was able to buy, even if it’s a small gap. But if we’re thinking to reach all 25M estimated eligible children, we need to be able to procure 100M+ treatments. We’re not even considering at this stage options for expanding the age target, or increasing the n. of doses, all points that are being explored by the research community. SMC market comparison, 2015 vs 2016

Shaping the market Supported the introduction of child-friendly, dispersible SP+AQ Administrative support (registration, packaging) Advocating for accelerated ERP process Support to additional manufacturers So, what have we done to help shape the market and contribute to this trend? The project encouraged the acceleration of the development of a child-friendly, dispersible formulation, and supported its approval by strongly advocating for fast-tracking the QA approval processes. As a result, 80% of the drugs purchased by the project in 2016 were in the dispersible form. We’re also supporting a second manufacturer at this stage in entering the market, and you can see here some frames from a video that show the solution of new dispersible tablets in the water. We do that again through technical assistance, as well as supporting the decision-making process of new manufacturers by helping them develop business cases to enter the SP+AQ market. By and large, things are moving according to plan, though with some obstacles here and there, in particular related to how the pharmaceutical sector works.

2014

2015

2016

Feasibility at scale The other side of the strategic intent expected us to assess a number of things, in order to demonstrate the feasibility at scale. While this is not the scale we would have wished for 2015 – with roughly half of the available drugs we had to revise our ambitions – we still managed to reach over 3 million children in the seven countries.

Feasibility at scale Achieving high administrative coverage This is data from the different national malaria control programs, with an average coverage across the region ranging from 85.2% during cycle 1 and 94.3% during cycle 4 in year one, and 76.9% to 97.2% in 2016. Coverage varies, and quite significantly, by country, and there are known issues with administrative coverage that we will touch upon later on and in follow-up discussions. This year we had specific difficulties with drugs regulatory agency in Nigeria, which because of the size of the country affected general coverage results in cycle one. In any case, SMC at scale seems feasible, if complex.

Feasibility: is SMC safe? Safety monitoring and support to pharmacovigilance: Are there any major safety concerns in distributing SMC to a large target population? showed signs of severe adverse reactions We also wanted to confirm that SMC was safe, particularly considering that this is a preventive treatment. We know from critical trials that SMC drugs were relatively safe, but at the scale of millions of children we wanted to closely monitor the safety profile of the drugs, and check whether there were any safety concerns in distributing these drugs to large numbers of children.

Feasibility and effectiveness Coverage verified by surveys: Are the right children reached (age / geography)? Are they reached during all 4 cycles and effectively protected? ADMIN DATA Weighted average coverage in the region: 91% ______________________________________________ SURVEY DATA Received at least 4 treatments: 56% Received at least 3 treatments: 74% We also wanted to make sure that the intervention was effective, from a number of points of view. So we’ve been carrying out coverage surveys to verify that the data we obtained from administrative sources are reliable: do we reach the right children, meaning those of the right age, and from the right places? And more importantly, do we reach them for four full cycles so that they are effectively protected? If we take the example of Burkina Faso, we can see that administrative coverage and absolute numbers of children treated continue to increase during the 4 months of SMC, even going beyond MoH-set targets.

Feasibility and effectiveness Reduction of malaria cases in children under 5 Preliminary results from a number of countries show that it works indeed, with a reduction of up 65% in malaria cases linked to SMC administration in The Gambia, for instnace.

Human resources But at what cost? This was one of the question we set out to answer, as one of the objective of the project is to improve the affordability of SMC delivery. We wanted to understand how we can bring down the costs of delivery, and to do that we needed to identify the key cost drivers, both within and without the project, but also ask the question: is SMC actually that expensive, considering the size of the intervention. And some preliminary results from costing research seem to tell us that No, SMC is not awfully expensive, in fact it looks relatively inexpensive. Across the region the total median cost is just under 4.5$ per child reached per year, though again there are variations across countries. What we will also do in the coming months is to try to identify the benefits of SMC, especially in terms of savings to health systems. And also confirm whether SMC is cost-effective even when implemented at scale.

At what cost? What are the benefits? Is SMC cost-effective at scale? What are the key cost drivers? Is SMC expensive? But at what cost? This was one of the question we set out to answer, as one of the objective of the project is to improve the affordability of SMC delivery. We wanted to understand how we can bring down the costs of delivery, and to do that we needed to identify the key cost drivers, both within and without the project, but also ask the question: is SMC actually that expensive, considering the size of the intervention. And some preliminary results from costing research seem to tell us that No, SMC is not awfully expensive, in fact it looks relatively inexpensive. Across the region the total median cost is just under 4.5$ per child reached per year, though again there are variations across countries. What we will also do in the coming months is to try to identify the benefits of SMC, especially in terms of savings to health systems. And also confirm whether SMC is cost-effective even when implemented at scale. What are the benefits? Is SMC cost-effective at scale?

Summary Contributed to shaping the market: SMC at this scale is: Influencing supply Driving the introduction of a child-friendly formulation SMC at this scale is: Feasible Reasonably priced Safe Probably effective if all conditions are met

Challenges Supply chain: Definition of targets Slow international QA processes Slow registration processes in country Complex post-shipment inspection procedures Difficult balance between donor accountability and country ownership of commodities. Definition of targets Late planning and quantification processes Lack of reliable figures (triangulation) Government accountability: Delays in contracting and expenses justifications Uncertainties in planning

Beyond ACCESS-SMC Transition to other sources of funding Uncertainties about funding: Keep the momentum for institutional demand Expand further Government ownership (beyond MoH/NMCPs): Financing strategy Coordination: Joint planning and procurement Data collection and monitoring (impact, resistance, PV) Regional coordination

Beyond ACCESS-SMC Cost-saving initiatives: Targets and duration of SMC Innovative delivery approaches Prospects for integrating interventions  SMCPlus Targets and duration of SMC Expand the target group (10 yrs) Plan the potential development for drug resistance Expand the geographical scope to SP resistant areas While SMC can by many measure be considered a relatively inexpensive intervention, the pressure on stakeholders to cut costs where possible will remain. It will thus be important to test innovative approaches for delivering SMC that can result in cost savings while maintaining high coverage and quality of the intervention. It may be down to economies of scale as we expand the scope of the intervention, but cost savings or at least cost synergies may also result from the integration of other interventions that can use common platform, or simplification of delivery approaches. And there are key concerns and strategic implications related to the scope and the duration of SMC. For instance, should we expand the target group to include children up to 10 yrs old? Some recommend it, some countries already do implement it, though it’s not as yet a WHO recommendation. But we should start asking ourselves whether we should do it in other countries, what would be the consequences on feasibility, on the market for drugs, the potential positive effects on malaria transmission, but also the potential risk of increasing drug resistance. Related to this, we need to plan in advance for the likely development of drug resistance, by identifying new drug combinations that could outsmart this process and give extra oxygen to the SMC intervention, or some other form of chemopreventive options with similar features. This could also help us expanding SMC-like interventions in areas where currently SP resistance make the available drugs not viable.

Conclusions SMC is not a magic bullet, but in the Sahel it is an effective complementary prevention approach to malaria control. The time to invest is now, while drugs are still efficacious, and in line with a multi-faceted effort to reduce malaria- related cases and deaths in line with the WHO Malaria Strategy. Continued support to research is necessary to monitor effectiveness and drugs efficacy Over 10M children who could potentially benefit from this intervention currently are not due to lack of funding The time to invest is now, before drugs stop working

Thank you www.access-smc.org