Olivia Seifert
Rare Disease Day presents a time to reflect on the progress made in understanding and addressing the unique challenges that rare diseases bring – and the hurdles that remain. Over the past year, several significant developments have shaped the rare disease landscape, from new regulatory policies and technological advancements to major advocacy efforts.
Policy shifts and regulatory milestones de
Regulatory agencies in the US and Europe have implemented significant measures over the past year to enhance the development and approval pathways for rare disease treatments.
In the US, the Food and Drug Administration’s (FDA) Rare Disease Endpoint Advancement (RDEA) Pilot Program actively supported the development of novel efficacy endpoints for rare disease drugs – allowing drug developers to establish alternative clinical measures, such as biomarkers or patient reported outcomes, to assess a prospective therapy’s impact – which could help lead to faster drug approvals and more effective therapies. The FDA also put forward a proposal to establish a Rare Disease Innovation Hub to foster collaboration between multiple FDA offices and centres to streamline the development of rare disease therapies.
Meanwhile, in Europe, discussions have continued regarding changes to the EU Orphan Drug Regulation, with proposals to adjust market exclusivity periods to incentivise orphan drug innovation – for example, by shortening these periods for drugs that generate high revenues or extending them for treatments addressing high unmet needs. Such adjustments could have lasting impacts on the affordability of these drugs and the speed at which treatments reach patients. Further, the European Rare Diseases Research Alliance (ERDERA), launched in September 2024 with an estimated budget of 380 million Euros and comprising over 170 public and private organisations, aims to build on the advancements made by previous EU-funded rare disease projects to accelerate the availability of therapies and improve the lives of 30 million rare disease patients in Europe and beyond.
Progress in rare disease drug approvals
In 2024, significant strides were made in the approval of treatments for rare diseases, underscoring the growing momentum to address these unmet medical needs – a shift driven through regulatory incentives, technological advancements, and the growing financial potential of the orphan drug market.
The FDA approved 26 orphan-designated drugs out of 50 total approvals – accounting for over 50% of all drug approvals in 2024. This highlights a continuing trend in the industry towards specialised treatments for smaller patient populations, reflecting the rise of precision medicine therapies. Meanwhile, the European Medicines Agency (EMA) put forward recommendations for the authorisation of 15 orphan drugs, several of which received orphan designation from the European Commission by year-end.
Notable FDA approvals within the last year include IntraBio’s drug Aqneursa for Niemann-Pick disease type C – a rare and fatal genetic disorder that causes the accumulation of lipids in cells, leading to progressive neurological and organ dysfunction – as well as SpringWorks Therapeutics’ Gomekli treatment for neurofibromatosis type 1 – a rare genetic disorder characterised by the growth of tumours on nerves throughout the body.
AI and technological advancements to drive faster diagnosis
Over the past year, significant progress has been made in advancing the diagnosis and early detection of rare diseases through the development of new cutting-edge technologies and initiatives. These developments hold promise to ultimately drive improved patient outcomes.
Artificial intelligence (AI) is also helping to streamline the drug discovery process by automating tasks that traditionally take years, such as identifying promising drug candidates, designing new molecules, and predicting their efficacy.
For example, researchers at Boston Children’s Hospital leveraged AI to analyse electronic health records and identify undiagnosed rare disease patients, helping to cut diagnostic timelines – a significant issue for rare disease patients who often endure a long and difficult “diagnostic odyssey” before receiving a correct diagnosis. In parallel, a recent study introduced GestaltMML, a multimodal machine learning approach that combines facial images, demographic data, and clinical notes to improve rare genetic disease diagnosis.
In the past week, Healx announced the first patient dosing in the Phase 2 trial of HLX-1502, an AI-discovered investigational therapy for neurofibromatosis type 1 (NF1), a rare genetic disorder with limited treatment options. This marks a significant shift towards AI-driven drug discovery, an approach that holds the potential to dramatically accelerate the identification of new therapies for rare diseases.
Additionally, the Newborn Genomes Programme in the UK was officially launched in 2024, with plans to sequence 100,000 newborn babies to detect rare genetic conditions early – a vital initiative towards reshaping early intervention strategies and better understanding a larger number of rare genetic diseases.
The impacts of patient advocacy
Patient advocacy groups have driven meaningful change in the past year, influencing both research priorities and policy decisions. Efforts from the EveryLife Foundation’s Rare Disease Caucus in the US contributed to additional funding being secured for the FDA Rare Neurodegenerative Disease Grant Program, aimed at funding clinical trials that evaluate the efficacy and safety of therapies for individuals living with rare neurogenerative diseases.
The Rare Disease Moonshot initiative – a collaboration between nine advocacy groups – celebrated its two-year anniversary in 2024 and gained significant momentum in its goal of uniting global stakeholders to address disparities in rare disease research and care.
The road ahead: Navigating the future of the rare disease landscape and improving understanding of patient populations
While progress is being made, many challenges remain – with approximately 95% of rare diseases still lacking therapies in the US. Drug pricing and access continue to represent major issues for the development of rare disease therapies, with the cost of new gene therapies sometimes reaching millions of dollars per patient per year. Equity in rare disease research also remains a challenge, as non-Caucasian populations are underrepresented in many clinical trials and genetic studies – hindering the development of effective treatments for all populations, and contributing to healthcare disparities. Further, the lack of awareness and understanding of rare diseases within both the medical community and in the general public impacts time-to-diagnosis for individuals living with rare diseases and is a contributing factor towards insufficient funding for research.
Better data is a key part of addressing these challenges, helping to refine disease burden estimates, inform diagnosis strategies, and improve access to treatment. HealthLumen’s recent genetic database analysis on Fabry disease – suggesting that it may be 3 times as prevalent as current estimates indicate – demonstrates how leveraging genetic databases to determine robust prevalence data can help identify currently under-served and unrecognised patient populations. Last year, we also launched our free AlleleAtlas tool as a service to the rare disease community, aimed at helping to improve understanding around the prevalence and characteristics of rare genetic disease patient populations.
Next week, HealthLumen’s CEO, Simon Lande, will be attending two rare disease events: the 4th Crick Rare Diseases Conference and REACT Congress. If you are planning on attending either event and would like to know more about our work, please feel free to reach out to arrange a meeting.