Improving awareness and treatment of rare diseases requires concerted effort from all stakeholders, particularly patient advocacy groups, to drive policy changes from the ground up.
By definition, rare diseases refer to medical conditions with a specific pattern of clinical signs, symptoms, and findings that affects fewer than or equal to 1 in 2000 persons. Collectively, there are approximately 6,000 to 8,000 diseases identified as rare, which affect about 400 million sufferers worldwide or 3% to 8% of the global population.
In Southeast Asia, the rare disease landscape and management remain unclear, given the lack of epidemiological data. The exact number of diseases in the region is unknown, due to limited research and reporting infrastructure, making it an under-recognised burden in this region. It is estimated about 45 million people, or 9% of the region’s population, suffer from rare diseases. The prevalence and types of rare disease vary from country to country due to differences in genetic makeup.
In Singapore, approximately 2,000 to 3,000 people are affected by rare diseases, while in Thailand, it is estimated that 3 million individuals have a rare disease but only 20,000 patients receive treatment, a dismal 0.0067%! In Malaysia, the Ministry of Health (MOH) has listed about 500 rare diseases in its database which can be managed, but only 25% to 70% of patients receive treatment.
Hence, rare diseases are not quite as rare as we might think. While each disease may only affect a small number of people, collectively they affect more people than all types of cancer combined. Thousands of patients are forced to navigate an extremely complex and challenging landscape of misdiagnosis, and lack of access to, or high cost of, treatment.
While Southeast Asian countries have made noticeable progress towards universal healthcare coverage, the focus has been on primary preventive care and acute care, leaving significant gaps in the management of chronic rare diseases.
Are rare diseases overlooked by medicine?
Individuals with rare disease face unique trials and tribulations that are often so complex, that their quests for diagnosis through treatments are often referred to as ‘medical pilgrimages’. A study found that 25% of individuals with undiagnosed disorders endured this ‘patient odyssey’ for five to 30 years before diagnosis, with the same percentage travelling to different regions during the process. Nearly half of these patients received at least one misdiagnosis before eventually receiving an accurate one.
One of the issues is that physicians are typically not trained to recognise diseases that occur infrequently. During their studies, future physicians are often taught that while evaluating a patient they should first consider a common diagnosis and not a rare one. Although most physicians would likely face the diagnosis or treatment of a rare disease in the course of their professional lives, many lack the knowledge to care for rare disease patients. This leads to misdiagnosis or inappropriate medical intervention.
The wide disparities in healthcare in Southeast Asia, including access to specialised care and diagnostic tools is another stumbling block in the journey of rare disease management. Healthcare systems vary greatly from country to country and within indivdiual countries in this region, further complicating the patient’s journey towards obtaining accurate diagnoses.
In Malaysia, for example, the majority of healthcare facilities do not offer rare disease or genetic screening services. The country only has four hospitals offering genetic and metabolic clinic services, and 13 rare disease specialists. Meanwhile, in Thailand there are only 22 geneticists available, mostly located in major cities, serving its population of 67 million people.
The absence of professional societies focused on rare diseases to support specialists, enable data collection, and share local experiences, further widen the gaps in expertise.
Inequitable funding for rare diseases
With small numbers of patients scattered across populations, rare diseases are a low priority for governments around the world, more so in low- and middle-income countries (LMICs). Limited understanding of rare diseases among the public, policymakers, and elected officials exacerbates stigma and discrimination, resulting in limited political and policy attention. This affects public health professionals, industry, academia, and healthcare professionals (HCPs).
Only a small fraction of national health budgets are typically allocated to the treatment of rare diseases, perpetuating the continuous and increasing financial impact on patients, health systems and economies. The funding gap for rare diseases is significant and will only widen without intervention.
According to a 2021 white paper, public reimbursement for rare disease drugs is uncommon and private insurance coverage is very low, especially in the LMICs. Additionally, patient registries and specific registration pathways for rare disease treatments are uncommon in most LMICs.
Some of the gaps in public funding for rare diseases include:
1. Funds being either absent or insufficient
2. Lack of rare disease strategy, governance, and legislation
3. Lack of plans for continuous provision of funds for rare disease by governments
4. Lack of public reimbursement for high-cost innovative drugs for rare disease
In Malaysia, access to treatment is limited, with government subsidies covering only specific enzyme replacement therapies and treatments for eligible patients at government hospitals. Other ASEAN countries rely mainly on industry subsidies, employer benefits, charitable efforts, or out-of-pocket payments for financing of rare disease treatment.
The combination of these challenges often leave patients having to choose between financial catastrophe or foregoing required treatment. And many patients choose latter.
Impact of misdiagnosis on patients
For over 40% of rare disease patients, misdiagnoses cause treatment delays. Some patients are at risk of receiving the wrong treatment entirely, with potentially fatal results.
Yu Jia Xuan from Selangor, Malaysia, was diagnosed with spinal muscular atrophy (SMA), a disease affecting about one in 20,000 live births. Her journey to obtaining accurate diagnosis through treatment took at least 18 months, including multiple visits to different healthcare facilities and specialists. She was eventually diagnosed with SMA in 2019, at 18 months old. Unfortunately, she was not able to access any treatments specifically for SMA as there were no available treatments in Malaysia at the time of her diagnosis.
In 2022, a novel therapy targeting SMA became available in Malaysia, but the cost was prohibitively high for the family, as Jia Xuan’s father was unemployed at the time. It was only with the support and financial aid provided by non-governmental organisations and an international patient advocacy group that Jia Xuan finally gained access to the medication for her lifelong treatment.
Diagnosed at 29 years old, Thai patient Nishapa Leeleartkij, now 43, continues to suffer from ulcerative colitis (UC). Even with an accurate diagnosis, Nishapa faced challenges in accessing specialised medication due to the high cost. With Thailand's low incidence of UC, at about 0.2 per 100,000 population and limited availability of affordable treatment options, she had to rely on assistance from a non-profit organisation to subsidise part of her treatment cost.
In addition to the physical burden of inaccurate treatments or treatment delays, many patients carry emotional and psychological burdens of enduring an undiagnosed illness for a prolonged period leading to social stigma and disadvantages in education and employment.
As a result, some patients may exclude themselves from the formal health system out of frustration and end up never receiving proper diagnosis or treatment.
Overcoming systemic challenges
Dialogues between the various stakeholders across the healthcare system, and between different national systems, are imperative to tackle the systemic challenges surrounding rare disease management.
According to the 2021 IQVIA White Paper commissioned by Roche, one of the major hurdles for policymakers in particular will be identifying appropriate funding solutions in line with the needs of their population, and sustainable ways to adopt them. This should be supported by adequate evidence for rare disease funding prioritisation, and strategic guidance on approaching sustainable funding solutions.
1. Development of robust evidence on current funding gaps that contribute to raising awareness and understanding of rare diseases needs
2. Capturing perspectives of patients and caregivers
3. Adoption of specific multidisciplinary, evidence-based health technology assessment (HTA) framework for rare diseases that does not focus on cost-effectiveness
4. Engagement of payers and policymakers based on unified approaches informed by the rare disease community
5. Alignment of stakeholders’ incentives to ensure sustainability and continuity of funding solutions.
Patients and their caregivers will continue to play a critical role in catalysing strategic solutions as will identifying best practices and learning from international experts and institutions treating and studying rare disease. More extensive local and regional collaboration for data sharing on rare disease can address the lack of patient data. Policymakers can engage international experts to support decision making in countries where rare disease data and specialists are lacking.
Positive developments in the region
Generally, countries in Southeast Asia have made healthy progress towards rare disease management in recent years. While the extent of progress varies between countries, there are several noteworthy initiatives which are bridging the treatment and management gaps:
1. Clinical guidelines to aid quicker diagnosis
A recent report in APAC showed that only one in three rare disease patients receives evidence-based care, largely due to a lack of standardised treatment guidelines for rare diseases.
In 2023, an expert panel of endocrinologists from nine Asia Pacific (APAC) countries gathered to create the first evidence-based recommendations for optimising and standardising X-Linked Hypophosphatemia (XLH) care in the region. XLH, a rare disease causing bone pain and fractures in adults and bowed legs in children, lacked treatment guidelines tailored to the APAC context, as previous guidelines were based on Western experiences and were often irrelevant due to regional differences in population makeup and availability of resources.
“XLH affects one in 20,000 people and is often mistaken for rickets, causing delays in diagnosis. Correct diagnosis, treatment, support, and care for people with XLH are vital as the disease is both progressive and lifelong. The consensus recommendations are the first of their kind in APAC, as well as a milestone in advancing knowledge of XLH in APAC, which was developed by, and for, HCPs from across the APAC region,” says Professor Craig Munns, Mayne Professor of Pediatrics and Director of Child Health Research Centre, in South Brisbane, Queensland, Australia, who spearheaded the initiative.
2. Establishment of national funding
The treatment for rare diseases are often prohibitively expensive, costing patients hundreds of thousands of dollars annually, with patients typically requiring lifelong administration. Singapore has led the way in this region with the establishment of the Rare Disease Fund (RDF) in July 2019 to provide long-term, financial support to patients with rare genetic diseases who require high-cost treatments.
The RDF is a national multi-stakeholder charity fund that combines community donations with three-for-one government matching, and is intended to be a last-line of support after government subsidies, insurance and other financial assistance. Prior to the establishment of RDF, only a few rare disease patients received subsidies from the industry, hospital funds, or MediFund, the national means-tested fund for indigent patients; indigency defined as when a patient does not have the financial means to pay for their medical expenses on top of expenses of day to day living.
3. Patient advocacy to drive policy changes
Awareness is a critical factor in rare disease management as it leads to greater public and private involvement. Thankfully, public awareness of rare diseases in ASEAN has increased in the past five years with most countries having their own patient support groups. Patients have been essential in convincing policymakers to address rare diseases in healthcare policy.
In Thailand, for example, patients have largely influenced its health policy and Universal Coverage Scheme (UCS). Despite the high costs and rarity of haemophilia, with only 1,828 known patients, the Thai Haemophilia Patient Club meticulously gathered data and case studies from its networks and used them to convince the government to include haemophilia treatment into its UCS benefits package.
Singapore hosted the first Rare Disease Asia Conference in February 2015, which brought together 25 patient support groups from 13 countries. It has also established the Rainbow Across Borders patient support organisation that acts as a regional umbrella alliance for rare diseases. This organisation promotes regional collaboration among patient support organisations, while focusing on developing the rare disease registry and directory across Asia.
“The variety of patient advocacy groups, particularly those focused on rare diseases, have encouraged various stakeholders in Singapore to factor in the patient’s voice when making critical decisions related to the cost-effectiveness of treatments, including determining medications which should be included in subsidised drug lists,” explained Professor John CW Lim, Executive Director of the Centre of Regulatory Excellence (CoRE), Duke-National University of Singapore Medical School (Duke-NUS).