Novartis Social Business

Image area

The Novartis Initiative Committed to malaria control and elimination Patients are at the core of our mission to discover and develop innovative medicines.

With this in mind, we have set up a holistic program to Overall, from 2001 to 2015, an estimated 6.2 million fight malaria: the Novartis Malaria Initiative. lives have been saved and the upward disease spiral reversed thanks to a concerted international Resting on four key pillars – treatment, access, effort to scale up interventions1. We are proud of capacity building, and research and development the remarkable public health milestones these – the Novartis Malaria Initiative is tailored to best collaborations have helped to achieve. meet patient needs. It has become one of the largest access-to-medicine programs in the healthcare industry, measured by the number of patients reached annually. Innovation

Since 2001, working with a range of organizations, we have provided more than 750 million treatments for nt e A tm c adults and children, without profit, to more than 60 a c e e r s countries, contributing to a dramatic reduction of the T s malaria burden in Africa.

R g & in d D il u b y cit Capa

Partnerships Preface Image area

The last 15 years have brought great progress in the Finally, adequate financing for malaria is crucial. This fight against malaria. Of the 106 countries that had funding must be available to the poorest African ongoing malaria transmission in 2000, some 102 have countries with the highest burden of disease, and met the MDG target of reversing the incidence of also to the countries that have made great progress malaria1; 57 of those have reduced malaria incidence toward elimination, but still face potential malaria by more than 75% by 2015 while a further 18 countries resurgence. Such resurgences will only be avoided have reduced malaria incidence by 50-75%2. While through ongoing investment and vigilance. we should celebrate these successes, we must also recognize and overcome key challenges that could We must build upon the extraordinary progress of slow down the current momentum. the last 15 years. With effective strategies, excellent collaboration, smart research and adequate First, emerging drug and insecticide resistance resources, we will maintain our momentum and must be actively confronted. We must therefore continue to drive toward malaria elimination, country continue our vigorous efforts to develop new drugs by country and region by region. and insecticides to respond to emerging resistance. The work of Novartis in researching and developing Our ultimate goal is nothing less than zero human the next generation antimalarials is an essential malaria on planet earth. Let us all remain focused on component of the successful fight against malaria. this common objective and intensify the collective work we have begun to ensure we see it through to its end. Second, political commitment and high ambition must be sustained. Decreased political commitment at Professor Sir Richard Feachem, either the domestic or international level would derail KBE, FREng, DSc(Med), PhD momentum. History has proven that gains in reducing Director of the Global Health Group at the malaria can be fragile, and that success can be too University of California, San Francisco easily reversed. Founding Executive Director of the Global Fund to Fight AIDS, TB and Malaria 4 | Malaria Initiative 2016

Treatment – Malaria is preventable and curable, yet it is still one of the most deadly diseases in developing countries.

Although nations across Africa, where the incidence disease, with -based combination therapies of malaria is the highest, have scaled up malaria (ACTs) as they represent the best treatment currently control strategies, effective control and treatment available2. present enormous logistical difficulties, as many at-risk populations live in extreme poverty in remote ACTs are recommended over older treatments rural areas1. Reaching remote communities with poor such as chloroquine, sulfadoxine-pyrimethamine transport systems and ensuring drug supplies do not and artemisinin monotherapies, as parasites have 2 run out represent some of the greatest hurdles to developed resistance to these drugs . The WHO malaria elimination. estimates that the number of ACT treatment courses delivered to the public and private sectors have The World Health Organization (WHO) emphasizes increased from 11 million in 2005 to 337 million in 2014 the importance of treating uncomplicated – of these, more than 66% were for the public sector1. falciparum malaria, the most dangerous form of the

Leading the path toward malaria elimination Two decades of public health milestones

License agreement signed between Novartis Novartis commits to make the fight against malaria and Chinese partners a key aspect of the company’s access-to-medicine programs

1994 1997 Malaria Initiative 2016 | 5

Image area

The proportion of children under 5 years with The Novartis ACT is indicated for the treatment malaria who were treated of acute, uncomplicated Plasmodium falciparum with an ACT is estimated to have increased from less malaria3. It combines two antimalarial agents with than 1% in 2005 to 16% in 20141. This proportion falls complementary effects: substantially short of the target of universal access for • Artemether, a derivative of artemisinin which is malaria case management. A primary reason is that a extracted from the sweet wormwood plant Artemisia high proportion of children with fever are not taken for annua, provides fast relief from malarial symptoms care or use the informal private sector, where they are and is rapidly eliminated4. less likely to obtain ACTs for treatment.1 • Lumefantrine has a longer-lasting effect and kills residual parasites4. As this compound has never Pioneering a standard of care for millions of been deployed as a monotherapy5, the potential risk patients of resistance to lumefantrine may be lower than with other agents. In 1999, Novartis was the first healthcare company to launch a fixed-dose ACT, and in 2009 the first dispersible ACT tailored to meet the needs of children, the most vulnerable to malaria.

First regulatory approvals for The Novartis ACT is the first Signed Memorandum of Understanding Novartis ACT in Africa (Gabon), one brought to market in a with the WHO to supply Novartis ACT Switzerland and UK fixed-dose form without profit to the public sector

1998-1999 1999 2001 6 | Malaria Initiative 2016

“Novartis is in the fight against malaria for the long haul. We will continue to partner with the best institutions and companies and intensify our research efforts to develop efficient compounds against malaria to eventually eliminate the disease. But we cannot do this on our own, neither as a company nor as an industry. We need support from politics, technology and academia as well as the public at large, because we can only win this fight together.” Joerg Reinhardt, Chairman of the Board of Directors of Novartis AG Malaria Initiative 2016 | 7

In 2010, Novartis was awarded the Prix Galien USA England Journal of Medicine in 2016, showed that all award in the category of the “Best Pharmaceutical the drugs had acceptable cure rates. However, AL was Agent” for its antimalarial treatment. associated with the fewest adverse effects, adding to the existing body of evidence of the safety profile of The Novartis antimalarial treatment has become a AL in pregnancy16. standard of care for millions of patients around the world: Responding to the unmet medical needs of • With a cure rate of over 95%*,6-10 and a demonstrated children safety profile6-11, this was the first fixed-dose ACT brought to market, and prequalified by the WHO for Children are the most vulnerable to malaria: in its quality, safety and efficacy12. 2015, approximately 70% of all deaths from malaria 1 • Approved in more than 60 countries, this was the occurred in children under the age of five . Malaria first and only ACT approved by the US Food and remains a major killer of children, particularly in sub- Drug Administration in 200913. Saharan Africa, taking the life of a child every two minutes.1 Over the past three years, on average, a treatment was made available to approximately 200,000 malaria Yet, until a few years ago there was no child-friendly patients every day. treatment for these vulnerable patients.

Evaluating safety and efficacy in pregnant Ahead of the call from the WHO and UNICEF for “child-sized” medicines, the Novartis Malaria Initiative women started developing, in collaboration with Medicines for Malaria during pregnancy remains a significant health Malaria Venture17, a sweet-tasting ACT specifically for risk to the mother and unborn child. Malaria can cause children10. adverse outcomes, including abortion, anaemia and low infant birth weight14. Various studies to evaluate the efficacy and safety of ACTs, including artemether- lumefantrine (AL), in pregnant women have been conducted. The Novartis pediatric

Two prospective studies in Zambia14 and Rwanda15, antimalarial treatment is the first: performed in collaboration with the WHO from 2004 to 2009, evaluated the safety of the Novartis ACT • Dispersible ACT specifically tailored in more than 3,000 pregnant women with malaria. Results suggested that exposure to AL in pregnancy for infants and children (≥5 kg) is not associated with particular safety risks in terms of perinatal mortality, malformations or developmental • Pediatric ACT approved by impairment14,15. The outcomes of these studies are Swissmedic (2008)17 aligned with the current WHO recommendations on the use of ACTs for the treatment of uncomplicated • Pediatric ACT prequalified by the Plasmodium falciparum malaria during the second and 12 third trimesters of pregnancy. WHO (2009) and recommended for use in the WHO treatment guidelines5 A multicenter, randomized, open label four-arm study in four African countries involving a total of 3,428 • Sweet-tasting antimalarial to mask people evaluating the safety and efficacy of AL, amodiaquine-artesunate, -artesunate and the bitter taste of lumefantrine dihydroartemisinin-piperaquine, published in the New

The Novartis treatment is the first Novartis is the first company Production scale-up to ACT listed on the WHO’s Model List to obtain WHO prequalification 100 million treatment capacity of Essential Medicines for its ACT per year

2002 2004 2005-2006 8 | Malaria Initiative 2016

Launched in 2009, this was the first ACT meeting This development program has spanned about WHO requirements for a pediatric antimalarial12. The four years starting with a rigorous preliminary medicine contains the same concentration of active pharmaceutical evaluation and development, followed ingredients as the regular tablet, but in a dispersible by a bioequivalence study. The new dosage strength formulation that is easier to give to babies and was approved by Swissmedic in November 2013 and children weighing 5 kg and above, which helps to received WHO prequalification in July 2015 making it ensure that this population receives the correct dose. the first artemether-lumefantrine (AL) with a reduced The sweet-tasting formulation disperses quickly in pill burden available for public sector procurement. small amounts of water which enhances its use in To date, the treatment has been launched in more young children5. than fifteen African countries in the private sector.

Since its launch, more than 300 million treatments Supporting treatment adherence through have been delivered without profit to more than 40 packaging countries, mainly in Africa. This makes it the first pediatric ACT to have been delivered in such large We have developed innovative packaging for our quantities. antimalarial treatments to help patients take the medication properly. In addition to written instructions, the packaging uses pictograms that remind patients of how many tablets to take and when. The packaging “The story of the Novartis child-friendly is color-coded to help identify appropriate dosing ACT is proving that partnerships are key, regimens for different body-weights. not only to develop new, high-quality This is particularly important in areas with low levels of education, where illiteracy is common and the disease medicines for malaria but also to deliver transmission high. these to vulnerable populations.” The packaging was further enhanced to support David Reddy, Chief Executive Officer, treatment adherence, with images of malaria parasites decreasing in number as the three-day course Medicines for Malaria Venture progresses.

We worked with PSI, a global health organization with programs targeting malaria, the Zambian Nurses Reducing the pill burden for adults Association, the University of Oslo, the KEMRI- We have developed a new dosage strength of our ACT University of Oxford-Wellcome Trust collaborative for adult patients which reduces the number of tablets program, Medicines for Malaria Venture (MMV) and to be taken during the treatment course from 24 to the World Health Organization (WHO) to develop 6 tablets, i.e. one tablet twice daily for three days this unique packaging – which received the “Drug instead of four tablets twice daily for three days. A Packaging Design Award” from the Healthcare 75% pill burden reduction has the potential to improve Compliance Packaging Council-Europe in 2009. treatment adherence and clinical outcomes.

Start of best practice sharing Driven by economies of scale, Healthcare Compliance workshops with national malaria Novartis more than halves the Packaging Council Award control program managers price of its ACT

2006 2006-2009 2009 Malaria Initiative 2016 | 9 10 | Malaria Initiative 2016

Access – Novartis has pioneered an untraditional non-profit business model to fight malaria.

Through a partnership with the World Health continuing to provide medicines on the same terms Organization (WHO) in 2001, we were the first company as before. Underscoring our long-term commitment, in the healthcare industry to commit to the supply of we work with a range of other partners involved in the antimalarial treatments to the public sector of malaria- procurement of treatment for public sector use. These endemic countries without profit. This joint effort has include UNICEF, UNITAID, the Global Fund to fight had immense health benefits, leading to the provision of AIDS, Tuberculosis and Malaria, the US President’s more than 750 million treatments and contributing to a Malaria Initiative, the United Nations Development dramatic reduction of the malaria burden in Africa1. Program, Doctors Without Borders, international procurement agencies and national procurement To further demonstrate its commitment, Novartis did partners. not enforce the patent for artemether-lumefantrine (AL), opening the door to other manufacturers Globally, the number of ACT treatment courses to supplement its efforts in increasing access to procured from manufacturers increased from 11 million medicines. Currently, there are 8 WHO prequalified in 2005 to 337 million in 2014 – Africa accounted for manufacturers of AL.2 98% of ACT deliveries in 2014 with more than half being doses for children3. Today, AL accounts for the In 2011, the 10-year formal alliance with the WHO largest volume of ACTs delivered (73% in 2013)4. came to an end, but we entered a new phase,

Prof. Zhou Yi-qing recognized Launch of the dispersible The Novartis antimalarial treatment is as “Inventor of the Year” for pediatric treatment with MMV the first ACT approved by the US FDA the Novartis ACT

2009 Malaria Initiative 2016 | 11

Expanding access in the private sector of malaria-endemic countries It is estimated that up to half of malaria patients in Africa do not have access to public health services and buy antimalarials from the private sector, at local market stalls and drug stores, where they often purchase sub-standard or counterfeit medicines because they are cheaper and available. This is particularly true for people living in urban townships and remote rural villages. We are therefore exploring novel distribution channels to improve access to high- quality antimalarials for people relying on the private sector. In particular, we are partnering with The Global Fund through an innovative financing mechanism, called the Private Sector Co-Payment Mechanism. Since 2010, more than 100 million Novartis treatments, including 58 million pediatric treatments, were provided through this channel.

In order to supplement these efforts and further expand access to ACTs in the private sector, we also launched an access program in 2012 in malaria- endemic countries. These countries were chosen based on multiple criteria including high unmet medical need; lack of access to quality ACTs in the private sector; or absence of Co-Payment Mechanism access programs. Importantly, this access program does not rely on donor funding, thus is more likely to be sustainable long-term. As part of this effort, we are also training staff in pharmacies and retail outlets in appropriate diagnosis and treatment of malaria.

“The progress that has been made toward significantly reducing the malaria burden in Africa will be quickly undermined if we do not tackle the endemic problem of poor quality antimalarials in the private sector. The issue urgently needs to be addressed through a collaborative effort between governments and the wider malaria constituency so we can ensure that all patients have access to the best antimalarials available.” Professor Bob Snow, Chairman of the Malaria Public Health Department at the KEMRI-Wellcome Trust

Prix Galien USA World Business and Development Award for Corporate Social Re­spon­sibility Award, United Nations by the Asso­ci­ation of Strategic Alliance Professionals

2010 12 | Malaria Initiative 2016

In the private sector, our activities focus on four • Limited visibility to district management on the tracks: medicine stock levels in their facilities • Collaboration with reputable local business partners • Difficulty in forecasting demand for the drug, in order to expand access to quality-assured ACTs resulting in emergency orders that require ramping and ensure effective local distribution channels up production and transporting the drug by air • Training of external field staff on the appropriate use • Inconsistent reporting of consumption and sporadic, of our antimalarial treatments, including provision of paper-based ordering patient information and educational materials • Distribution of appropriate dosage forms according In an effort to tackle stock-outs of antimalarials in to epidemiological data and patient needs, with a malaria-endemic countries, Novartis joined forces with special emphasis on infants and children private and public partners, including the Global Fund • Monitoring of the availability, accessibility and retail and various African health ministries. Called SMS for prices of our antimalarial treatments Life, the project uses mobile phones, tablet PCs and electronic mapping technology to track stocks of key Impacting lives with SMS antimalarials and other essential medicines in rural health facilities. The overall goal is to eliminate stock- Stock-outs of antimalarial medicines at the health outs, increase access to medicine and reduce the facility level in rural sub-Saharan Africa are a major number of deaths from malaria. barrier to the effective management of the disease. Lack of visibility of stock levels largely contributes to What makes this solution unique is that it has this problem. demonstrated it works in the targeted environment by reducing and eliminating stock-outs. It is flexible, In many African countries, supply chain problems expandable and scalable to support any number of make it difficult to get malaria medicines to patients. additional health facilities, countries and products. It can be deployed quickly (5,000 health facilities in 7 Barriers include: months) and at a total operational cost of less than • High stock-outs at rural health facilities, i.e. the point USD 80 per health facility per year. of care, where patients can get free drugs rather than having to pay for them at pharmacies or private clinics

Novartis Malaria Initiative honored with the World Business and Development Award by the UN Development Program, the International Chamber of Commerce and the International Business Leaders Forum for its contribution to the MDGs

2010 Malaria Initiative 2016 | 13

“The reward for success is not just the lives impacted, but the fact that there are now a number of companies, large and small, realizing they may have a license to operate that requires them to commit to diseases in parts of the world where they do not typically focus.” Dr. William Rodriguez, Research Associate, Harvard Medical School

The system automatically sends an SMS to all health Since its inception, SMS for Life has received facilities on a regular basis asking for their current numerous awards and recognitions, including the stock. Responses are collected and stored centrally 2012 Ethical Corporation Award for Best Corporate/ on a website, and reports generated and sent to NGO Partnership and Computerworld’s 21st Century key health staff in the country including the National Achievement Award in the Innovation IT category. Malaria Control Program. Reports are also made Earlier recognitions include the Wall Street Journal’s available via the Internet or mobile phone. Technology Innovation Award in the Health-Care IT category, being ranked #1 in Technology in the Health SMS for Life 1.0, the phone- and SMS-based version, category in the GBC Business Action on Health has been rolled out in more than 10,000 healthcare Awards, and a catalytic grant from The Innovation facilities in sub-Saharan Africa, including more than Working Group, part of the UN Secretary-General’s 3,000 facilities in Cameroon. Further, the solution is Every Woman Every Child effort, and the mHealth now being used to track bed nets, rapid diagnostic Alliance. tests (RDTs) and health data, as well as antibiotics, leprosy and tuberculosis medicines and blood As we are constantly looking for innovative ways supplies. to help improve access to medicines, in 2013, we joined forces with Malaria No More, a global charity, An enhanced version called SMS for Life 2.0, based to support Power of One, a fund-raising campaign to on tablet computers instead of text messages, help accelerate progress toward malaria elimination. can now track more stock items and more disease Over three years, Novartis partnered with Malaria surveillance indicators. The platform will also be No More to deliver malaria treatments to children used to deliver high-quality training directly to health in Africa. Every dollar donated served to treat a workers at their health facility. child with a confirmed case of malaria and Novartis matched the number of treatments funded by SMS for Life 2.0 is currently under advanced Novartis associates and the public – translating into discussions for implementation in Gabon, Nigeria and two treatments delivered for every dollar donated. Zambia. Overall, the campaign led to the delivery of 3.6 million treatments for children with malaria in Africa.

Wall Street Journal GBC Business Action SMS for Life honored with a catalytic Technology Innovation Award on Health Awards for grant from the UN Foundation and the for SMS for Life SMS for Life mHealth Alliance

2011 14 | Malaria Initiative 2016

Capacity building is a cost- effective and sustainable means of advancing health and development in developing countries.

Learning by sharing to better fight malaria Topics discussed at the workshops range from case management and utilization of rapid diagnostic In 2006, the Novartis Malaria Initiative introduced tests and ACTs to private sector engagement, workshops with managers of National Malaria Control awareness campaigns, forecasting, distribution, Programs (NMCP) in Africa. NMCPs, a part of health stock management, health impact measurement and ministries in African countries, are charged with innovative strategies to accelerate malaria elimination. overseeing malaria control interventions by setting A prime focus at these workshops has been the national standards and providing guidelines and collection of data from the field to quantify the impact technical assistance. of new malaria policies.

The NMCP workshops, held once a year, are Groundbreaking projects have emerged from these designed to share best practice and experiences meetings. For instance, as a result of discussions with between African countries, highlight successes and NMCP managers, Novartis substantially reduced the challenges, and discuss practical solutions to improve packaging size of its antimalarial treatment, making malaria control in endemic regions. To date, NMCP transport and storage more efficient. workshops have been held in Benin, Ethiopia, Kenya, Mali, Mozambique, Rwanda, South Africa, Tanzania, It was also at NMCP workshops that participants Uganda, and Zambia. raised the stock-out issue which led to the SMS for Life program to support more efficient stock management in rural health facilities.

100 million Novartis ACT treat­ments 500 million Novartis Novartis joins forces with Malaria No delivered in 2011 and a total of ACT treatments More on Power of One, a campaign to 100 million dispersible pediatric delivered to patients rally the global public to fight malaria treatments delivered since 2009

2011 2012 2013 Malaria Initiative 2016 | 15

“The greatest burden of the disease is felt at the household level since my daily income is generated almost entirely from agriculture. The debilitating nature of this disease puts our lives under constant threat.” Angeline Nyandiko, grandmother, Kenya

The availability of an ACT specifically tailored to Building capacity on the ground infants and children was also a key discussion topic during NMCP workshops as Novartis and Medicines We have more than a decade of experience in training for Malaria Venture collaborated to develop the endemic countries in international standards of Good dispersible pediatric formulation. Clinical Practice, in order for them to become self- reliant in the conduct of clinical trials. More recently, the Novartis Malaria Initiative’s program to expand access to affordable, quality-assured As part of a large 14,000-patient study we undertook malaria treatments in the private sector of African in Burkina Faso, we provided clinical research countries was also a result from previous NMCP and pharmacovigilance training to a team of 220 1 meetings. healthcare personnel .

Nigeria is the first country worldwide to SMS for Life wins Ethical Corporation Award for launch the new Novartis ACT in the private Best Corporate/NGO Partner­ship and is recognized market reducing the treatment course to among the top 100 innovative solutions at the forefront 6 tablets (from 24) of sustainable transformation by Sustainia

2013 16 | Malaria Initiative 2016

“Malaria is one of the top ten diseases that we treat in our health district. About 50 percent of the patients come for malaria treatment. Depending on the season, we often treat up to 15-20 patients a day with ACTs.” Dr. Zaina Mfouka, District Malaria Health Officer, Tanzania

The ALIVE study (Artemether-Lumefantrine In We have developed case management training for Vulnerable patients: Exploring health impact) nurses and educational materials for healthcare on the safety monitoring of the Novartis ACT in workers to improve the diagnosis and treatment of rural Tanzania showed that by offering healthcare malaria. Other initiatives have included workbooks workers frequent training and refresher sessions on to educate health workers about the disease, foster pharmacovigilance, safety monitoring and reporting is a dialogue with patients and train other co-workers. possible, even in rural settings where health services are limited2. Further, to support the introduction of our dispersible formulation for infants and children, we developed Training healthcare personnel and a workbook and educational poster for healthcare communities workers available in different languages. Several NMCPs in African countries have included these Training health professionals and workers in diagnosis materials into their own training programs. and treatment, informing the public about treatment availability and measuring the impact of malaria More recently, we have produced an educational story policies are key elements for endemic countries to booklet for children and their families. combat the disease. Using full color illustrations, it presents key information In 2005, in collaboration with the WHO, Novartis built on how to prevent and treat malaria for readers with the capacity of extension health workers in the Tigray low literacy levels. region, northern Ethiopia. This led to the rational use of medicines and huge cost savings for the Tigray In Uganda, together with the Scort Foundation, The Health Bureau. In the same year, Novartis carried out Football Club Social Alliance and the Ministry of nationwide training of healthcare workers in Zambia Health, the Novartis Malaria Initiative is working to to support knowledge dissemination on malaria educate the young generation about malaria, the treatment guidelines. country’s leading cause of sickness and death.

Novartis awarded with Malaria No More’s Novartis reaches milestone of providing 700 million Global Corporate Citizenship Award for its treatments without profit to malaria-endemic countries, leading role in the fight against malaria of which 250 million dispersible pediatric treatments since 2009

2013 2014 Malaria Initiative 2016 | 17

Booklets telling the story of a young girl named We also source the Active Pharmaceutical Ingredients Tatu who is fighting malaria were distributed to (APIs) of our antimalarial treatments from China. “young coaches” to help them explain malaria As part of our collaboration, every year, we spend prevention, symptoms, diagnosis and treatment to several weeks on the ground, training suppliers and their communities. The Football Club Social Alliance transferring knowledge and technology on the latest counts world-renowned partner clubs including FC manufacturing methods. This technology transfer has Basel 1893 in Switzerland. In another initiative in enabled them to meet international quality and health, Mozambique with the Peace Corps Volunteers, we safety and environment standards in the production of supported the distribution of Tatu booklets to more APIs, and allowed the registration of their facilities by than 2,000 mothers and children as part of the Stomp drug regulatory authorities. Out Malaria program. Our partners have played key roles in the scale-up of Transferring technology and know-how production and remain critical to our ability to satisfy demand. In China and Madagascar, we are providing indirect support to local farmers in the cultivation of Artemisia annua, the source of artemisinin.

Support starts during the seed ordering of Artemisia annua in January where we forecast requirements and commit to certain volumes from the upcoming annual harvest. Farmers are provided with planting material and training in Good Agricultural Practice for Artemisia annua cultivation to ensure high-quality returns. In addition, a dedicated biomass manager provides seeds and technical support to farmers.

Novartis builds strong antimalarial Through Power of One, Novartis Power of One: 3 million pipeline with two new compounds associates help raise USD 500,000 pediatric treatments in Phase 2 clinical development to provide treatments for children delivered to Zambia and with malaria 600,000 to Kenya

2014 2015 18 | Malaria Initiative 2016 Malaria Initiative 2016 | 19

Research & Development – We are applying our expertise in drug discovery to the next generation of malaria treatments.

Ever since we pioneered artemisinin-based Research, conducted by an international team of combination therapies (ACTs) in 1999, we have scientists at the Novartis Institute for Tropical Diseases, continued to leverage both the expertise of our large the Genomics Institute of the Novartis Research research organization and our unique network of Foundation and the Swiss Tropical and Public Health external partners to research and develop best-in- Institute (Swiss TPH) led in 2010 to a promising class compounds against malaria. new drug candidate1 for drug-resistant malaria, which achieved Proof of Concept (PoC) in 2012. Discovering next-generation treatments About 20 patients infected by one of the two main malaria-causing parasites took part in the PoC study Since 2006, we have been working with various conducted in Bangkok and Mae Sot near the Thailand/ partners including the Genomics Institute of the Burma border where first signs of resistance to current Novartis Research Foundation, the Swiss Tropical and therapies had been reported. In just five years, this Public Health Institute, and the Biomedical Primates compound was moved into Phase 2 clinical trials. Research Center (Netherlands) to discover the next generation of antimalarial drugs. The discovery This compound belongs to a new class called­ program is supported in part by the Wellcome Trust, spiroindolones, the first true innovation since the the Singapore Economic Development Board and launch of ACTs. It kills the blood stages of Plasmodium Medicines for Malaria Venture (MMV). falciparum and through a novel

300 million dispersible pediatric Novartis new dosage strength Dr Youyou Tu receives treatments delivered by Novartis ACT receives WHO prequalification, the Nobel Prize for her since 2009 without profit making it the first AL with a reduced pill discovery of artemisinin burden for public sector procurement in 1972

2015 20 | Malaria Initiative 2016

mechanism of action, including parasites that have Setting a standard in treatment efficacy developed drug resistance. It also appears to be and safety effective against the sexual forms of the parasite, so could help prevent disease transmission. Over twenty Novartis-sponsored clinical studies, corroborated by more than sixty independent In 2011, the same group of scientists announced trials, spanning 15 years with more than 12,000 the discovery of a second new dual-acting class of patients, have demonstrated the positive safety4-10 antimalarial compounds – called imidazolopiperazines and efficacy4-8 profile of our ACT treatment across – that act on both blood and liver infections2,3. The different populations and regions. Further, post- malaria parasite first infects the liver before moving to marketing surveillance, based on the delivery of more red blood cells and causing symptoms. than 750 million treatments to date, has not identified any new safety concerns. Preventing the disease through seasonal chemoprophylaxis will require that future antimalarials In an effort to address the unmet needs of pregnant work against both blood and liver stages to bring women with malaria, together with the WHO, we us closer to the goal of malaria elimination. The conducted the largest prospective study in Zambia compound achieved PoC in 2013 and has also moved between 2004 and 2008 to evaluate the safety of into Phase 2 clinical trials. our treatment in this specific patient population11. The outcomes of the study were aligned with the current Further, our scientists are working on additional WHO recommendations on the use of ACTs for the projects which include a back-up compound to one of treatment of uncomplicated Plasmodium falciparum the compounds now in Phase 2 clinical development, malaria during the second and third trimesters of various blood and liver stage actives with novel pregnancy15. mechanisms of action.

“I know many people who have lost family members due to malaria ... This is a disease that tears apart families and makes them poor. It makes me sad.” Emis Mtonga, father, Zambia Malaria Initiative 2016 | 21

The development of the dispersible formulation “It is very important to keep one step for infants and children weighing 5 kg and above consisted of four studies8,12. Two pharmacokinetic ahead of the parasite and provide studies were performed in healthy volunteers in innovative treatments to support Europe. The other two were carried out in sub- Saharan Africa, one in healthy schoolchildren to malaria elimination efforts.” evaluate the medicine’s palatability – a key factor in aiding compliance in children’s medicines – and one Thierry Diagana, Head of the Novartis in infants and children with malaria. The dispersible Institute for Tropical Diseases formulation is as effective and well tolerated as the standard adult tablets10, and encourages improved adherence to the drug regimen.

How to counter drug resistance? As the lumefantrine component in the Novartis treatment has never been used by itself to treat Over the years, in many parts of the world, malaria15, unlike the partner drugs of all other ACTs, the malaria parasite has become resistant to the risk of resistance against the treatment may be conventional treatments, such as chloroquine, lower compared to other ACTs. Yet, in an effort to and other antimalarials when used on their own. anticipate any potential challenge to the effectiveness As a consequence, the WHO changed its of its drug, Novartis is currently leading research treatment guidelines to recommend the use to develop new drug candidates for drug-resistant of ACTs for Plasmodium falciparum malaria. malaria. These would be the first new antimalarials not belonging to the artemisinin class. Yet, today, early signs of resistance to have appeared in five countries of South-East Asia resulting in delayed parasite clearance from the blood13. Even though ACTs may take longer to act in these areas, their overall efficacy is not affected as long as the partner drug to artemisinin remains effective14. 22 | Malaria Initiative 2016

Patient impact – The combination of prevention and treatment to fight malaria is yielding unprecedented benefits for patients.

From 2000 to 2015, malaria mortality rates fell requires at least 80% of houses in targeted areas to by 60% around the world1. During this period, an be sprayed to reach its full potential. estimated 6.2 million malaria deaths, of which 5.9 million among children under 5, were averted globally1, Prevention efforts have made a major difference. The primarily as a result of a scale-up of interventions. proportion of the population having access to vector control (ITNs and/or IRS) in sub-Saharan Africa has These major achievements have substantially increased from 2% in 2000 to 59% in 2014. In 2015, contributed to achieving the malaria-specific target more than half of the population in sub-Saharan Africa of the Millennium Development Goal (MDG 6 target (55%) is now sleeping under an insecticide-treated C) with a 37% decline in global malaria incidence , compared to 2% in 2000. Although this since 20002. Vector control has been, and still is, result represents a substantial increase since 2000, instrumental in reducing malaria transmission at the it falls short of universal coverage of this preventive community level. Long-lasting insecticide-treated measure. nets (LLINs) and indoor residual spraying (IRS) with insecticides that kill the mosquitoes carrying Yet, the proportion of the population at risk that is malaria parasites are effective in a wide range of protected by IRS has declined globally from a peak of 1 circumstances. 5.7% in 2010 to 3.4% in 2014 .

The World Health Organization (WHO) recommends Prevention alone is not sufficient. Treatment is LLIN coverage for all persons at risk of malaria. Indoor needed to save lives and eliminate malaria parasites, spraying remains effective for 3 to 6 months but preventing further transmission of the disease. “With a holistic approach including prevention and treatment, there’s a high potential to eliminate the disease in Zambia, but we need continued attention on the disease.” Dr. Mabvuto Kanjo, former Case Management Specialist, Ministry of Health, Zambia

Since 2002, the WHO recommends the use of ACTs Combining interventions for maximum impact and as a result, most African countries have adopted in Zambia, Ethiopia, Rwanda and Senegal the Novartis ACT as a first-line treatment. Rapid diagnostic tests (RDTs) also play a crucial role in Zambia fighting drug resistance as they help to ensure ACTs The scaling up of malaria prevention strategies and are only administered to patients who actually need vector control has dramatically reduced the disease them. burden in Zambia, the first African country to adopt the Novartis ACT as first-line therapy in 2003. An Beyond prevention and treatment, building capacity integrated malaria control program distributing ACTs in malaria-endemic countries to strengthen their and bed nets and applying indoor residual spraying healthcare systems and deliver high-quality was scaled up during 2003-20073. Following the interventions is essential to ensuring long-lasting program, malaria mortality and morbidity were health impacts. dramatically reduced. In-patient malaria cases and deaths declined by 61% and 66%, respectively, in Importantly, malaria elimination requires sustained and 2008 compared with the reference period (2001- aggressive efforts in the long term. This is why it is 2002) before the program3. Under-five mortality was crucial that public donors and private companies alike also reduced from 16.8% in 2002 to 7.5% in 2013. continue to scale up funds and R&D toward malaria Although far below the recommended universal elimination. coverage rate, the proportion of children under 5 sleeping under a bed net has nearly doubled from 24% in 2006 to 41% in 20134. 24 | Malaria Initiative 2016

Ethiopia awareness8. In spite of this, Rwanda has unfortunately Similar positive outcomes were measured in Ethiopia, experienced an upsurge in malaria cases in 2009, where 68% of the population lives in at-risk areas 2012 and 2013. Nonetheless, with the significant with an estimated 12 million suspected malaria cases reduction in malaria cases over the past 10 years, the each year5. The Novartis ACT was launched as country aims to achieve malaria pre-elimination status first-line therapy in 2004. As a result of combined by 2018.8 interventions, including the delivery of ACTs in the public sector and more than 64 million LLINs Senegal between 2005 and 20146, the prevalence of malaria Large-scale deployment of the Novartis ACT parasitemia in Ethiopia is now 1.3%6, and the incidence and RDTs began in 2007 in Senegal and of malaria deaths in children aged under 5 was 12.6% progressed rapidly, leading to a 3% prevalence of in 2010/2011, compared with 21.1% in 2003/2004.5 parasitologically-confirmed malaria cases in 2009 The country has also set up an elaborate health (from 36% clinical cases in 2001). The proportion extension program involving around 38,000 volunteers of deaths attributable to malaria in children under 5 who visit individual households, teach people about was also drastically reduced from 30% to 7% in the sanitation, do rapid diagnostic tests and treat positive same timeframe, and by 2009, malaria accounted for cases7. 4% of all deaths in the country. To further reinforce the interventions and successes in the fight against Rwanda malaria, in 2008, Senegal introduced a new type of Rwanda adopted the Novartis ACT as first-line health worker, the village malaria worker, who provides therapy in 2006. It reported a significant decline in RDT testing and ACT treatment to patients in the malaria incidence. Between 2005 and 2012, malaria household. This program is now active in almost morbidity decreased by 87%, while malaria mortality 2,000 rural villages across 13 regions. Senegal, like declined by 74%. This decrease is attributed to several Rwanda, hopes to achieve pre-elimination status by measures including the distribution of LLINs, ACTs 20189. in all public health facilities and improved patient Malaria Initiative 2016 | 25

Looking ahead

We have witnessed remarkable progress in the have never been deployed as a monotherapy, hence fight against malaria in the past 15 years – thanks where no resistance has yet developed. to integrated strategies combining prevention and treatment, as well as efforts from endemic countries Affordability and accessibility in malaria control. Effective treatments need to be made affordable Yet, the enormous progress achieved appears to have to patients in the public and private sector alike. slowed down in recent years. International funding Initiatives such as the Private Sector Co-Payment for malaria control has leveled off, and is projected to Mechanism and the Novartis access program in the remain substantially below what is required to achieve private sector can help bridge the gap. universal coverage of malaria interventions. Case management To achieve the milestones and goals set out in the Malaria elimination requires effective case WHO’s Global Technical Strategy for Malaria 2016- management to scale up malaria diagnostic testing, 2030, malaria investments will need to increase treatment and surveillance systems. substantially above the current annual spending of USD 2.7 billion. The annual investment will need to Strengthening these three pillars presents significant reach an estimated USD 8.7 billion by 2030 to reduce challenges. Programs such as SMS for Life support malaria case incidence and mortality rates by at least these efforts by tracking surveillance data in addition 90% by 20301. Further, additional funding of USD 673 to providing stock visibility of diagnostics and million will be required annually for R&D.1 treatments.

Key steps to malaria elimination Patient adherence A sustained effort is required to continue to scale Continued information is necessary to maximize up access to treatment in order to reduce malaria treatment adherence and successful health outcomes. mortality by 90% by 2030, as advocated by the Further, formulations tailored to the needs of patients, WHO’s Global Technical Strategy for Malaria 2016- such as pediatric dispersible tablets or formulations 2030. While there are challenges, including a global that reduce pill burden, and user-friendly packaging funding gap partly due to declining donor financing, can enhance treatment adherence. Fostering disease weak health systems and the potential emergence of awareness and a timely treatment-seeking behavior drug and insecticide resistance, there is hope. Efforts among patients is also key to adherence. must focus at all levels of the malaria “chain,” from quality of medicines to countering parasite resistance. Parasite resistance

Quality Research and Development to discover the next generation of antimalarials is needed in case The use of monotherapies and sub-standard resistance to ACTs emerges. It is therefore important antimalarials should be stopped to prevent the to develop new classes of treatment that are one step development of parasite resistance. Quality-assured ahead of the parasite should resistance to current ACTs provide one way to slow the potential spread therapies occur. Efforts should also focus on radical of drug resistance. Renewed international attention cure, prevention and development of prophylactic should also be given to deter counterfeits. Malaria is treatments. best fought using treatments with compounds that

“Thanks to initiatives like the Novartis Malaria Initiative, people can have hope. We will be able to really tackle this disease and one day maybe, for the next generation, there will be a malaria-free world.” Professor Awa Marie Coll-Seck, Minister of Health, Senegal 26 | Malaria Initiative 2016

References

Page 2: The Novartis Malaria Initiative 1. WHO World Malaria Report 2015. Available at: http://apps.who.int/iris/bitstream/10665/200018/1/9789241565158_eng.pdf?ua=1

Page 3: Preface 1. WHO World Malaria Report 2015. Available at: http://apps.who.int/iris/bitstream/10665/200018/1/9789241565158_eng.pdf?ua=1 2. Accelerating progress on HIV, tuberculosis, malaria, hepatitis and neglected tropical diseases, A new agenda for 2016-2030, WHO. Available at: http://apps.who.int/iris/bitstream/10665/204419/1/9789241510134_eng.pdf

Pages 4-8: Treatment 1. WHO World Malaria Report 2015. Available at: http://apps.who.int/iris/bitstream/10665/200018/1/9789241565158_eng.pdf?ua=1 2. WHO Malaria Fact Sheet No. 94, January 2016. Available at: http://www.who.int/mediacentre/factsheets/fs094/en/ 3. Novartis. Coartem® International Package Leaflet. April 2012. 4. White NJ, van Vugt M, Ezzet F. Clinical pharmacokinetics and pharmacodynamics of artemether-lumefantrine. Clin Pharmacokinet 1999; 37:105–125. 5. WHO Guidelines for the Treatment of Malaria: Third Edition (2015). Available at: http://www.who.int/malaria/publications/atoz/9789241549127/en/ 6. van Vugt M, Wilairatana P, Gemperli B, Gathmann I, Phaipun L, Brockman A et al. Efficacy of six doses of artemether-lumefantrine (benflu- metol) in multidrug-resistant Plasmodium falciparum malaria. Am J Trop Med Hyg 1999; 60:936–942. 7. van Vugt M, Looareesuwan S, Wilairatana P, McGready R, Villegas L, Gathmann I et al. Artemether-lumefantrine for the treatment of multidrug-resistant falciparum malaria. Trans R Soc Trop Med Hyg 2000; 94:545–548. 8. Lefèvre G, Looareesuwan S, Treeprasertsuk S, Krudsood S, Silachamroon U, Gathmann I et al. A clinical and pharmacokinetic trial of six doses of artemether-lumefantrine for multidrug-resistant Plasmodium falciparum malaria in Thailand. Am J Trop Med Hyg 2001; 64:247–256. 9. Hatz C, Soto J, Nothdurft HD, Zoller T, Weitzel T, Loutan L et al. Treatment of acute uncomplicated falciparum malaria with artemether- lumefantrine in nonimmune populations: a safety, efficacy, and pharmacokinetic study.Am J Trop Med Hyg 2008; 78:241–247. 10. Abdulla S, Sagara I, Borrmann S, D’Alessandro U, Gonzalez R, Hamel M et al. Efficacy and safety of artemether-lumefantrine dispersible tablets compared with crushed commercial tablets in African infants and children with uncomplicated malaria: a randomised, single-blind, multicentre trial. Lancet 2008; 372:1819–1827. 11. Falade C, Makanga M, Premji Z, Ortmann CE, Stockmeyer M, De Palacios PI. Efficacy and safety of artemether-lumefantrine (Coartem®) tablets (six-dose regimen) in African infants and children with acute, uncomplicated falciparum malaria. Trans R Soc Trop Med Hyg 2005; 99:459–467. 12. WHO Prequalified Medicines List. http://apps.who.int/prequal/lists/API/2016/API_PQ-List_V3_19February2016.xlsx 13. Novartis Press Release. “Coartem® receives FDA approval becoming first artemisinin-based combination treatment (ACT) for malaria in the US.” (April 2009) http://www.malaria.novartis.com/downloads/press-releases/2009-04-coartem-receives-fda-approval.pdf 14. Manyando C, Mkandawire R, Puma L, Sinkala M, Mpabalwani E, Njunju E et al. Safety of artemether-lumefantrine in pregnant women with malaria: results of a prospective cohort study in Zambia. Malar J 2010; 9:249. 15. Rulisa S, Kaligirwa N, Agaba S, Karema C, Mens PF, de Vries PJ. Pharmacovigilance of artemether lumefantrine in pregnant women followed until delivery in Rwanda. Malar J 2012; 11:225. 16. Four Artemisinin-Based Treatments in African Pregnant Women with Malaria. The PREGACT Study Group. N Engl J Med 2016; 374:913-927March 10, 2016DOI: 10.1056/NEJMoa1508606. 17. Novartis Press Release. “Novartis and Medicines for Malaria Venture launch Coartem® Dispersible, the first ACT developed for children suf- fering from malaria.” (2009). http://www.malaria.novartis.com/downloads/press-releases/2009-01-launch-of-coartem-dispersible.pdf

Pages 10-13: Access 1. Novartis Annual Report 2015. Available at: https://www.novartis.com/sites/www.novartis.com/files/novartis-annual-report-2015-en.pdf 2. WHO Prequalified Medicines List. http://apps.who.int/prequal/lists/API/2016/API_PQ-List_V3_19February2016.xlsx 3. WHO World Malaria Report 2015. Available at: http://www.who.int/malaria/publications/world-malaria-report-2015/en/ 4. WHO World Malaria Report 2014. Available at: http://www.who.int/malaria/publications/world_malaria_report_2014/report/en/

Pages 14-17: Capacity building 1. ClinicalTrials.gov identifier: NCT01256658. 2. Kabanywanyi AM, Mulure N, Migoha C, Malila A, Lengeler C, Schlienger R, Genton B. Experience of safety monitoring in the context of a prospective observational study of artemether-lumefantrine in rural Tanzania: lessons learned for pharmacovigilance reporting Malar J 2010; 9:205. Malaria Initiative 2016 | 27

Pages 19-21: Research & Development 1. White NJ, Pukrittayakamee S, Phyo AP, Rueangweerayut R, Nosten F, Jittamala P, Jeeyapant A, Jain JP, Lefèvre G, Li R, Magnusson B, Dia- gana TT, Leong FJ. Spiroindolone KAE609 for falciparum and vivax malaria. New England Journal of Medicine. 2014 July 31;371(5):403-10. 2. Leong FJ, Zhao R, Zeng S, Magnusson B, Diagana TT, Pertel P. A first-in-human randomized, double-blind, placebo-controlled, single- and multiple-ascending oral dose study of novel Imidazolopiperazine KAF156 to assess its safety, tolerability, and pharmacokinetics in healthy adult volunteers. Antimicrobial Agents and Chemotherapy. 2014 Nov;58(11):6437-43. 3. Kuhen KL, Chatterjee AK, Rottmann M, Gagaring K, Borboa R, Buenviaje J, Chen Z, Francek C, Wu T, Nagle A, Barnes SW, Plouffe D, Lee MC, Fidock DA, Graumans W, van de Vegte-Bolmer M, van Gemert GJ, Wirjanata G, Sebayang B, Marfurt J, Russell B, Suwanarusk R, Price RN, Nosten F, Tungtaeng A, Gettayacamin M, Sattabongkot J, Taylor J, Walker JR, Tully D, Patra KP, Flannery EL, Vinetz JM, Renia L, Sauerwein RW, Winzeler EA, Glynne RJ, Diagana TT. KAF156 is an antimalarial clinical candidate with potential for use in prophylaxis, treatment, and prevention of disease transmission. Antimicrobial Agents and Chemotherapy. 2014 Sep;58(9):5060-7. 4. van Vugt M, Wilairatana P, Gemperli B, Gathmann I, Phaipun L, Brockman A et al. Efficacy of six doses of artemether-lumefantrine (benflumetol) in multidrug-resistantPlasmodium falciparum malaria. Am J Trop Med Hyg 1999; 60:936–942. 5. van Vugt M, Looareesuwan S, Wilairatana P, McGready R, Villegas L, Gathmann I et al. Artemether-lumefantrine for the treatment of multidrug-resistant falciparum malaria. Trans R Soc Trop Med Hyg 2000; 94:545–548. 6. Lefèvre G, Looareesuwan S, Treeprasertsuk S, Krudsood S, Silachamroon U, Gathmann I et al. A clinical and pharmacokinetic trial of six doses of artemether-lumefantrine for multidrug-resistant Plasmodium falciparum malaria in Thailand. Am J Trop Med Hyg 2001; 64:247–256. 7. Hatz C, Soto J, Nothdurft HD, Zoller T, Weitzel T, Loutan L et al. Treatment of acute uncomplicated falciparum malaria with artemether- lumefantrine in nonimmune populations: a safety, efficacy, and pharmacokinetic study.Am J Trop Med Hyg 2008; 78:241–247. 8. Abdulla S, Sagara I, Borrmann S, D’Alessandro U, Gonzalez R, Hamel M et al. Efficacy and safety of artemether-lumefantrine dispersible tablets compared with crushed commercial tablets in African infants and children with uncomplicated malaria: a randomised, single-blind, multicentre trial. Lancet 2008; 372:1819–1827. 9. Falade C, Makanga M, Premji Z, Ortmann CE, Stockmeyer M, De Palacios PI. Efficacy and safety of artemether-lumefantrine (Coartem) tablets (six-dose regimen) in African infants and children with acute, uncomplicated falciparum malaria. Trans R Soc Trop Med Hyg 2005; 99:459–467. 10. Hamed K, Grueninger K. Coartem®: a decade of patient-centric malaria management, Expert Rev. Anti Infect. Ther. 10(6), 645–659 (2012). 11. Manyando C, Mkandawire R, Puma L, Sinkala M, Mpabalwani E, Njunju E et al. Safety of artemether-lumefantrine in pregnant women with malaria: results of a prospective cohort study in Zambia. Malar J 2010; 9:249. 12. Abdulla S, Amuri B, Kabanywanyi AM, Ubben D, Reynolds C, Pascoe S et al. Early clinical development of artemether-lumefantrine dispersible tablet: palatability of three flavours and bioavailability in healthy subjects.Malar J 2010; 9:253. 13. Status report on artemisinin and ACT resistance, WHO, September 2015: http://www.who.int/malaria/publications/atoz/status-rep-artemisinin-act-resistance-sept2015.pdf 14. World Health Organization. Global Report on Antimalarial Drug Efficacy and Drug Resistance: 2000–2010. 15. WHO Guidelines for the Treatment of Malaria: Third Edition (2015). Available at: http://apps.who.int/iris/bitstream/10665/162441/1/9789241549127_eng.pdf

Pages 22-24: Patient impact 1. WHO World Malaria Report 2015. Available at: http://www.who.int/malaria/publications/world-malaria-report-2015/en/ 2. Achieving the malaria MDG target: reversing the incidence of malaria 2000-2015, September 2015, WHO and UNICEF: http://apps.who. int/iris/bitstream/10665/184521/1/9789241509442_eng.pdf?ua=1 3. Chizema-Kawesha E, Mukonka V, Mwanza M et al. Evidence of substantial nationwide reduction of malaria cases and deaths due to scale-up of malaria control activities in Zambia, 2001–2008. World Health Organization, Zambia 19–23 January. 4. Fighting Malaria and Saving Lives, Zambia, President’s Malaria Initiative, 2015: http://www.pmi.gov/docs/default-source/default-document-library/country-profiles/zambia_profile.pdf?sfvrsn=16 5. Malaria Operational Plan FY 2014, Ethiopia, President’s Malaria Initiative: http://www.pmi.gov/docs/default-source/default-document- library/malaria-operational-plans/fy14/ethiopia_mop_fy14.pdf?sfvrsn=14 (accessed April 2016). 6. President’s Malaria Initiative. Ethiopia Malaria Operational Plan FY 2015. http://www.pmi.gov/docs/default-source/default-document- library/malaria-operational-plans/fy-15/fy-2015-ethiopia-malaria-operational-plan.pdf?sfvrsn=3 (accessed April 2016). 7. All eyes on Ethiopia’s Health Extension Program, USAID, 2016: https://www.usaid.gov/results-data/success-stories/all-eyes-ethiopia%E2%80%99s-national-health-extension-program-0 8. President’s Malaria Initiative. Rwanda Malaria Operational Plan FY 2015. http://www.pmi.gov/docs/default-source/default-document- library/malaria-operational-plans/fy-15/fy-2015-rwanda-malaria-operational-plan.pdf?sfvrsn=3 (accessed April 2016). 9. Senegal Malaria Operational Plan FY 2015, President’s Malaria Initiative: http://www.pmi.gov/docs/default-source/default-document- library/malaria-operational-plans/fy-15/senegal_mop_fy15.pdf?sfvrsn=4 PAGE 10

Page 25: Looking ahead 1. Global Technical Strategy for Malaria 2016-2030, WHO: http://apps.who.int/iris/bitstream/10665/176712/1/9789241564991_eng.pdf?ua=1&ua=1

Photo credits: Brent Stirton for Novartis AG (pages 3, 5, 6, 9, 11, 12, 13, 18) Mark Tuschman for Novartis AG (pages 1, 6, 16) The Novartis Malaria Initiative Novartis AG CH-4002 Basel, Switzerland ©Novartis AG 2016 NP4 Nr. GLEM/COARTEM/0071 www.malaria.novartis.com