Author
Jean-Michel Piedagnel
Hepatitis C is one of the most common causes of liver cancer and has affected millions of people. It was estimated that the prevalence of hepatitis C among the general population in Malaysia was 0.4%. The introduction of the first direct antiviral agent (DAA) in the market in 2013 became a game-changer for hepatitis C treatment, marked the emergence of the highly effective new treatment and has made it possible to imagine the global elimination of hepatitis C. However, there were several challenges in terms of affordability and accessibility to DAAs especially in lower-middle income countries (LMICs) such as Malaysia.
The success story of hepatitis C elimination in Malaysia
Malaysia and Thailand were excluded from voluntary licensing (VL) agreements for sofosbuvir, the main DAA to treat hepatitis C like many other countries such as China or most of Latin America. VL usually allows a limited number of ‘lower income’ countries to procure generic versions of sofosbuvir from manufacturers licensed by the patent holders. Malaysia stands out, as it expanded hepatitis C treatment through a series of strategic government-led initiatives.
One of the initiatives was to capitalise on the flexibilities provided in the World Trade Organization (WTO) Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS). Malaysia became the first country to invoke the TRIPS and issued a compulsory licence (CL) to enable the government-use (public non-commercial use) of sofosbuvir imported from Egypt in September 2017.
Another initiative was to invest in R&D to develop an alternative affordable treatment. In 2016, DNDi in collaboration with the Ministry of Health in Malaysia, the Ministry of Public Health in Thailand, Pharco Pharmaceuticals in Egypt, and Pharmaniaga in Malaysia with funding from MSF Transformational Investment Capacity (TIC) set a goal to develop a safe and effective DAA called ravidasvir that would be made accessible and affordable to all. This collaboration pursued an alternative drug research and development pathway: one with affordability at its core and founded on collaborations with LMICs through public-private partnership. This alternative pathway is in direct contrast to the traditional pharmaceutical research and development model, which focuses on profit maximisation and leadership from high-income countries.
There were lessons learnt throughout the hepatitis C journey in Malaysia. First, the Malaysian leadership was robust and committed to tackle this public health challenge. Hepatitis C virus (HCV) elimination almost became a national cause. Such political will was essential at key moments such as when the CL was issued or to include the ravidasvir, a new chemical entity in the WHO EML. Malaysia clearly was in the driving seat of this project—without doubt strategically, if not always technically. Many, who opposed this strategy of access through South-South R&D, underestimated the power and the value of such ownership.
Second, even if the contribution of an international partner like DNDi is required to coordinate a global project and fill the knowledge gaps, LMIC-based collaborations provide opportunities for learning, value chain creation, technology transfers, self-reliance, etc. These opportunities create a virtuous cycle that strengthens the ownership and leadership of Malaysia.
Third, it is possible to place affordability and public health priorities at the heart of drug development. The collaborative effort established by DNDi and partners illustrates the feasibility and desirability of partnerships for novel drug development in LMICs. Embracing alternative models, such as the one exemplified here, will contribute to our collective goal of promoting global health equity. These elements are aligned with components in Chapter 3 of Malaysia’s Health White Paper, which emphasises on strengthening the health system through effective public-private partnerships, stimulating research, innovation, strengthening public health functions, ensuring sustainable and equitable health financing.
Spearheading a 'Dengue Alliance' through global partnerships
Dengue fever is a disease caused by the dengue virus which is transmitted to humans via the bite of an infective mosquito. Although symptoms can be mild, severe dengue can be life-threatening sometimes. Up to 400 million people are infected with dengue worldwide each year. In recent decades, the global incidence of dengue has grown dramatically. Today, more than half of the world’s population is at risk and the disease is often a leading cause of death in some parts of the world. According to the World Health Organization (WHO), dengue fever is one of the top ten global health threats—it’s also the most rapidly spreading.
In addition, due to the impacts of climate change, swift urbanisation, and extensive international travel, the occurrence of dengue is on a rapid rise, placing considerable burden on healthcare systems in numerous lower-income nations. The highest infection rates due to dengue are seen in South Asia, Southeast Asia, and Latin America, with 70% of the burden of disease in Asia.
Numerous advancements have been made in managing the vector, including the introduction of Wolbachia-infected mosquitoes and spatial repellents, both of which have demonstrated success in several countries. Furthermore, there are few vaccines that are available now such as Takeda’s new dengue vaccine (TAK-003) and another vaccine under clinical trial. Despite the vaccines exhibiting approximately 80% effectiveness in preventing hospitalisation, the necessity for drugs to prevent the progression to severe disease in numerous patients remains evident.
While innovative vector control methods and dengue vaccines are on the horizon, the anticipated rise in dengue cases due to climate change and urbanisation suggests that a substantial number of patients will still necessitate hospitalisation. Therefore, alongside vector control methods and vaccines, there is a crucial need for a sustainable, integrated approach to dengue control, which includes the development of specific treatments—a facet often neglected.
An urgent requirement exists for a dengue treatment to mitigate the progression to severe disease, consequently reducing hospitalisations and complications associated with dengue. It is imperative that all such interventions, including vaccines, vector control, and drugs, are readily accessible to marginalised populations who bear the brunt of dengue’s impact.
Currently, most of the research done on dengue treatment is led by high income countries’ institutions with the support of colleagues and institutions in endemic countries. Most publications on dengue research have a main author from non-endemic countries. DNDi felt that it was essential to have a different approach and to capitalise on the experience of Malaysia’s leadership on HCV by empowering dengue endemic countries to lead the R&D on dengue treatment. It was crucial to ‘turn the table around’ and redistribute roles so that researchers in endemic countries would not support the research but lead it with the support of high-income countries.
Regaining control of the narrative about dengue as a disease rather than a virus and how it affects patients and health systems in endemic countries is essential to reconnect science with patients and needs and to stimulate some innovative approaches to dengue treatments. Therefore, establishing partnerships with like-minded entities in endemic countries, sharing the common objective of offering accessible and affordable diagnostics, treatments, and medical supplies is imperative.
The Dengue Alliance was launched in 2022 as a global partnership led by institutions from dengue-endemic countries that aims to develop affordable and accessible treatments for dengue. The dengue alliance is co-lead by Ministry of Health, Malaysia, Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand, Oswaldo Cruz Foundation (Fiocruz), Brazil, Translational Health Science and Technology Institute (THSTI), India, and Universidade Federal de Minas Gerais (UFMG), Brazil and DNDi.
Conclusion
Malaysia possesses significant potential to emerge as a hub for medical research, medical tourism, medical supply manufacturing, a global support centre for international organisations, and more. This potential is grounded in Malaysia’s abundant resources, diverse populations, and a pool of talented individuals. Malaysia is a multicultural country where people are used to working together which means it has an inherent ability to drive and to invest in global south-south partnership too.
