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Rare
diseases and roadblocks to affordable treatment Medicines for rare diseases are among the most expensive pharmaceuticals – costing up to millions per treatment – due in large part to patent protections. Compulsory licensing can offer a way out of the price trap. Chetali Rao RARE diseases, often referred to as orphan diseases, affect a small percentage of the population, yet their impact on individuals and families is profound. To date there are more than 7,000 known rare diseases affecting more than 300 million people globally, with 70% of these conditions starting from childhood.1 Children account for more than 50% of those affected and 3 in 10 of them normally die before the age of 5.2 These diseases are frequently progressive, chronic and disabling and can cause significant mortality and morbidity. While individually rare, there are common challenges and a huge unmet medical need faced by patients suffering from rare diseases globally. Historically, the development and approval of drugs targeting rare diseases was largely neglected by the pharmaceutical industry. However, spurred by regulatory incentives like the Orphan Drug Act in the US (1983), the Orphan Drug Regulation in the EU (1999) and similar policies elsewhere, a shift in the landscape of new drug approvals for rare diseases has taken place in recent years. Prior to 1983, only 38 drugs were approved to treat rare diseases; however, by the end of 2022, the US Food and Drug Administration (FDA) had approved 882 different drugs for use in the treatment of 392 rare diseases.3 In 2024, approximately 52% (26 out of 50) of new drugs approved by the FDA were for rare diseases.4 These advances are encouraging and reflect increasing recognition of the need for treatments targeting rare diseases, yet they are insufficient, considering that more than 95% of rare diseases still lack an FDA-approved treatment. This stark reality leaves millions of people living with a rare disease (PLWRD) clinging to hope for a cure or even basic disease management, and underscores the need for sustained innovation, increased investment and robust policy support to address the substantial gaps and unmet needs in this area. One of the most formidable challenges in addressing rare diseases is the scarcity of reliable epidemiological data, which hampers the translation of research findings into real-world interventions. The actual determination of rare diseases prevalence is challenging primarily due to the fragmented and non-standardised nature of available data. Information is derived from patchwork sources – ranging from published reports to registries, systemic reviews and anectodal evidence, each employing different methodologies and lacking uniform diagnostic criteria or coding systems.5 These inconsistences are greatly pronounced in the case of developing countries, due to limited clinical information, lack of universal health coverage and registries, and inadequate diagnostic capabilities.6 These factors significantly contribute to substantial underreporting and gross underestimation of the true burden of rare diseases. India is a striking example – prevalence and incidence data are available only for a limited number of relatively more common rare diseases like Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA). For many lesser-known rare diseases like Okur-Chung neurodevelopmental syndrome, there are no available prevalence or incidence estimates.7 Even for relatively better-known conditions like cystic fibrosis, there is a huge disparity in the data – the estimated number of diagnosed cases in India is 600, while research findings suggest that the patient population in the Indian subcontinent is greater than that of the United States – concrete epidemiological data remain scarce.8 Some estimates indicate that as many as 3,600 infants could be born with cystic fibrosis annually.9 Due to the diverse, complex and uncommon nature of rare diseases – compounded by the scarcity of epidemiological data – PLWRD have limited political visibility and are often deprioritised in the allocation of healthcare resources, including diagnostics and treatments. This lack of prioritisation has a detrimental effect not only for PLWRD but also for their families and caregivers who shoulder the emotional, financial and practical burden. A recent global estimate based on 3,585 rare diseases suggests that they affect nearly 3.5–5.9% of the world’s population corresponding to 263–446 million people,10 but when the broader ripple effect on family members and caregivers is taken into account, the figure reaches 1.05–1.4 billion people globally.11 The challenges faced by this community are exacerbated by experiences of discrimination and psychosocial consequences including social isolation, stigmatisation and limited opportunities for social inclusion.12 These hardships are often intensified by pervasive lack of public awareness and knowledge, which perpetuates misconceptions. Addressing these challenges therefore requires not only scientific and medical innovation but a concerted effort to raise awareness, foster inclusion and ensure that the voices of PLWRD and their families are heard and prioritised within health policy agendas. Recognising the collective impact rare diseases have on patients and their caregivers and the fact that this area has long remained on the periphery of health policy, the 78th World Health Assembly in May, in a historic milestone, saw member states of the World Health Organization (WHO) unanimously adopt the resolution ‘Rare diseases: a global health priority for equity and inclusion’.13 The resolution – the first of its kind within the WHO framework – mandates WHO to craft a comprehensive 10-year global action plan to improve diagnosis, treatment, access and equity, with the plan slated for presentation at the 81st World Health Assembly in 2028. Moving beyond symbolism, the resolution urges member states to incorporate rare diseases into their national health systems, enhance access to timely diagnosis and treatments, and establish robust registries and data systems. Though the resolution emphasises the financial burden of rare diseases, taking into cognisance the high cost of treatment and catastrophic out-of-pocket expenditure, it falls short of proposing specific funding mechanisms or global financial commitments to support its goal. The resolution mentions mobilising resources and exploring innovative funding models but lacks details on how to achieve this, especially for developing countries. A funding mechanism for rare diseases is a priority area as the majority of therapies developed for rare diseases come with an exceptionally high price tag, presenting a formidable barrier to accessibility and affordability. This challenge is compounded by the advent of newer cell and gene therapy treatments which have become some of the most expensive treatments introduced by the pharmaceutical industry. For example, Libmeldy, a gene therapy for the treatment of metachromatic leukodystrophy (MLD), is priced at nearly $4.3 million, while Elevidys for the treatment of DMD costs around $3.2 million per treatment. Without dedicated funding, the WHO resolution’s call for equitable access to medicines and assistive technologies may remain merely aspirational. In times of resource and budget constraints, health systems are struggling to make drugs for rare diseases accessible to PLWRD. High drug prices, driven by market exclusivity and limited competition, restrict access particularly for developing countries. A significant challenge lies in the inability of countries to address the monopolistic control pharmaceutical companies hold over rare disease medications due to their patent ownership. In numerous cases, these companies have prioritised patenting and monopolising their drugs over making them accessible to PLWRD. For instance, despite being available elsewhere, the drug Trikafta for treatment of cystic fibrosis has not been registered for marketing in India, although multiple patent applications have been filed for it. Most of the international discussions around rare diseases have failed to address the entrenched intellectual property barriers that render these critical life-saving medicines inaccessible. However, the World Trade Organization (WTO)’s Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) does contain several provisions that empower WTO member states to place public health priorities above intellectual property protections. Notably, the WTO’s 2001 Doha Declaration reaffirmed that the TRIPS Agreement should not impede WTO members from implementing measures necessary to safeguard public health and ensure access to affordable medicines. The adoption of the declaration was a monumental achievement for developing countries since it recognised the need to address their public health concerns and confirmed the right to use certain critical public health safeguards like compulsory licences (CLs) and parallel import flexibilities allowed under the TRIPS Agreement. Such provisions were incorporated to balance intellectual property rights with public health to ensure affordable access to life-saving drugs in resource-constrained settings. Although the declaration specifically referred to HIV/AIDS, tuberculosis and malaria, it covered all diseases, including non-communicable diseases.14 CLs enable governments to override patent exclusivities, yet, 30 years after the TRIPS Agreement’s entry into force, they remain underutilised, with only 65 documented cases of CLs and government use globally, which fails to systematically address drug affordability.15 Most governments have not fully leveraged the opportunities provided under the TRIPS Agreement to advance public health interests, particularly in the context of rare diseases. This reluctance can be attributed to the intense political and economic pressures exerted by the developed countries and pharmaceutical firms, which clearly prioritise the interests of the pharmaceutical patent holders. The situation is worsened by bilateral and regional free trade agreements (FTAs) which impose many ‘TRIPS-plus’ provisions that exceed the intellectual property protections under the TRIPS Agreement, limiting CL use. For example, many bilateral FTAs mandate a five-year data exclusivity period. This can block competition from generic drugs in the pharmaceutical market even after patent expiration or even in the absence of patent protection.16 Thus, even if a CL is granted to override a patent, generic manufacturers may still be prevented from entering the market until the data exclusivity period expires. Given the generic manufacturing capabilities of countries like India, China and Argentina, the drugs for rare diseases can be produced at a fraction of the current prices if patent encumbrances are addressed. However, patent protections have led to an absence of local production and have consequently kept these life-saving treatments out of reach of most patients suffering from rare diseases. Critics argue that compulsory licensing reduces incentives to undertake drug research and development (R&D), yet the sales of patented drugs, including those for rare diseases, are overwhelmingly concentrated in high-income countries such as the US and Europe, which together account for the vast majority of the revenue,17 suggesting that developing-country generics have minimal impact on profits. Studies clearly show that granting of CLs does not/has not hurt innovation.18 The high prices of drugs often far exceed R&D costs, thus clearly elucidating how business models place profit margins before patient well-being. A study by Dr Melissa Barber on the small molecule oral drug risdiplam for treating SMA reveals how the pharmaceutical industry often prioritises shareholders’ interests above patient needs. Despite its high market price of around $80,000 per patient per year (PPPY), risdiplam could be manufactured by a generic manufacturer at a fraction of the current cost.19 A generic manufacturer in India has produced the drug and has offered to sell it for a price as low as $4,000 PPPY. A similar pattern has emerged for Trikafta – where researchers have found that the drug could be produced for less than $6,000 PPPY, yet it is sold at an astonishing $326,000 PPPY.20 If a CL is granted for such a drug, it would significantly improve access for rare disease patients not only in India but globally. However, the launch of such generic drugs has been mired in legal disputes, resulting in prolonged delays for patients who urgently need access to these life-saving treatments. Despite recognising the potential to make rare disease drugs affordable and accessible, governments have refrained from pursuing compulsory licensing measures that would allow local generic manufacturers to produce these drugs. Similarly, governments have been largely silent on price transparency and pool procurement of such drugs. As a result, the promise of equitable access to treatments for patients with rare diseases remains largely unfulfilled and these life-saving medicines remain out of reach for those who need them most. Addressing these challenges in securing access to rare disease drugs requires not only political will but also a concerted effort to reform global intellectual property frameworks in a manner that prioritises public health over profits. No family should have to endure the heartbreak of seeing their child suffer from a disease for which a cure or treatment is available, simply because the drug is inaccessible. A few bold, targeted decisions can dramatically improve the lives of PLWRD and offer them the promise of a bright and equitable future. Chetali Rao is Senior Scientific Researcher and Legal Advisor to the Third World Network. Notes
*Third World Resurgence No. 363, 2025/2, pp 37-40 |
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