Each year, February 28 (or the 29th on leap years) marks the annual observance of Rare Disease Day, a global initiative that brings together patients, healthcare providers, sponsors, contract research organizations (CROs), and advocates to spotlight the challenges faced by those affected by rare diseases on the rarest day of the year. With the support of over 65 national alliance patient organization partners, Rare Disease Day 2025 will involve several awareness campaigns, community events, and educational programs held worldwide.  

The rare disease market is experiencing significant growth, driven by advancements in medical technology, increased research funding, and heightened awareness among healthcare professionals and patients. In 2024, the global rare diseases treatment market was valued at approximately USD $195.17 billion and is projected to reach USD $374.39 billion by 2030, growing at a compound annual growth rate (CAGR) of 11.6% from 2025 to 2030.  

In recent years, the therapeutic landscape for a diverse range of rare diseases has seen significant strides due to the emergence of precision medicine, which offers tailored therapeutic approaches based on individual genetic profiles, environmental factors, and specific disease mechanisms. Whereas before, these underserved patients were limited to a traditional one-size-fits-all approach to rare disease therapies, precision medicine now allows for the development of targeted interventions that address the unique characteristics of each rare condition.  

In this article, we will explore how precision medicine is transforming the treatment landscape for rare diseases. Specifically, the discussion will incorporate dual perspectives from oncology and neurology, two therapeutic areas that have been revolutionized with the use of targeted therapies. By leveraging key insights from experts in both fields, we will describe the broad applications for rare disease therapeutic research, as well as what challenges and opportunities await in 2025 and beyond. Read on to learn more! 

 

The Role of Precision Medicine in Rare Diseases 

What Is Precision Medicine? 

There’s a growing shift towards personalized medicine, where treatments are tailored to an individual’s genetic profile. This approach enhances the effectiveness of therapies and reduces adverse effects, especially crucial in managing rare diseases. Rare diseases individually have very small patient populations, but collectively, one in 10 people suffer from one of 10,000 different rare conditions worldwide. Because the majority consist of genetic rare disorders, often with distinct genetic or molecular signatures, precision medicine approaches can be especially beneficial for this therapeutic area. These approaches utilize advanced genetic testing, biomarker analysis, and molecular profiling to identify specific disease mechanisms and potential therapeutic targets unique to the individual.  

The rarity of these conditions has made developing drugs with traditional methods more challenging, but precision medicine allows for the creation of targeted interventions based on an  understanding of the underlying disease mechanisms [4]. This personalized approach to patient care is crucial for rare diseases because they affect small, genetically distinct populations who do not benefit from the “one-size-fits-all” treatment approach. More importantly, targeted therapies are designed with high specificity for disease-specific pathways while sparing healthy tissues, which reduces the risk of serious off-target adverse events. 

 

Key Trends in the Rare Disease Market: Advancements in Genomic Technologies 

Technological innovations, particularly in next-generation sequencing (NGS) and whole-genome sequencing (WGS), have revolutionized the diagnosis of rare diseases. These tools enable rapid and precise identification of genetic mutations, facilitating early and accurate diagnoses. 

 

Advances in Rare Disease Treatment 

As we go into 2025, technological capabilities in the industry are continuing to improve and sponsors are increasingly focusing on rare disease research by partnering with CROs that offer specialized expertise in clinical trials for orphan drugs. In recent years, the rise of precision medicine has led to several exciting advances in rare disease treatment and targeted therapy development, particularly for rare cancers or neurological disorders.  

 

Oncology 

In oncology, the development of targeted therapies for gastrointestinal stromal tumors (GIST) via specific inhibition of mutated tyrosine kinase receptors has significantly improved patient outcomes. Based on this promising research, the U.S. Food and Drug Administration (FDA) approved two new targeted therapies for the treatment of adult patients with advanced GIST. These included imatinib and avapritinib, which was the first targeted therapy approved for patients with GIST harboring a PDGFRA exon 18 mutation.

There have also been advances in personalized treatments for HER2-positive angiosarcoma, a rare aggressive vascular tumor, through the application of targeted antibody therapies. For example, in the phase 2 AO91902 trial (NCT04339738), combining cabozantinib (Cabometyx) with nivolumab (Opdivo) resulted in significant anti-tumor effects and was well-tolerated among patients with advanced angiosarcoma who had previously received taxane treatment. Read the full results from the AO91902 trial here. 

Additionally, synovial sarcoma is currently seeing promising developments with immunotherapy approaches and novel targeted agents that address specific genetic alterations. In August 2024, the US FDA approved the immunotherapy, afamitresgene autoleuecel (Tecelra® or afami-cel), for treating this rare soft tissue cancer. For the full press release, click here. 

 

Neurology 

In the realm of neurological diseases, Huntington’s Disease research has made significant strides with antisense oligonucleotides and gene-silencing therapies that target the underlying genetic cause. Back in June 2024, positive results were shared from the phase Ib/phase IIa clinical trial of WVE-003, an allele-selective antisense oligonucleotide that selectively silences mutant huntingtin (mHTT) protein. WVE-003 was generally well-tolerated and was able to lower mHTT levels in the cerebrospinal fluid considerably, relative to placebo. This trial represents the first-ever clinical demonstration of allele-selective silencing in any disease target. For the full trial results, read more here.  

Furthermore, spinal muscular atrophy (SMA) treatment has been transformed by revolutionary gene replacement therapies and RNA-modifying drugs, leading to significant improvements in patient survival and motor function. Since 2016, several targeted therapies, such as nusinersen, onasemnogene abeparvovec, and risdiplam, have received regulatory approval by the FDA and the European Medicines Agency (EMA) for the treatment of SMA. To learn more about the recent progress in gene-targeting therapies for SMA, click here. 

Finally, research in rare epilepsies, such as Rett syndrome, has also progressed with novel approaches targeting specific genetic and molecular pathways. In May 2023, the first patient in the REVEAL phase I/II trial with Rett syndrome was dosed with gene therapy, marking a major historical milestone for the disease. Another gene therapy, NGN-401, which delivers a full length MECP2 gene and EXACT, began testing in a phase I/II trial in late 2024. NGN-401 has received Regenerative Medicine Advanced Therapy (RMAT) designation from the US FDA for the treatment of Rett syndrome. 

 

Other Innovative Therapies Emerging from Clinical Development of Rare Disease Drugs 

Beyond advancements within the oncology and neurology therapeutic areas, several other innovative therapies are emerging in the rare disease space. For example, in Huntington’s Disease, a higher number of C-A-G repeats in patient DNA is associated with the earlier onset of the disease and the development of more serious forms. Precision medicine approaches with CRISPR-Cas9 genome editing technology have demonstrated the ability to recognize large domains with these repetitions, altering the region to reduce CAG repeats. This groundbreaking tool is also offering new opportunities to correct mutations associated with leukodystrophies in animal models or patient cells.

Another emerging precision medicine therapeutic approach in rare diseases is enzyme replacement therapy (ERT), which has emerged as a crucial intervention for lysosomal storage diseases (LSDs). ERT involves intravenously administering specific enzymes produced with recombinant DNA technology to primarily address abnormal enzyme deficiencies. To date, ERT has been approved by the FDA in several rare LSDs, including Fabry disease, type I Gaucher disease, and Batten disease. For example, Brineura (cerliponase alfa) was the first approved treatment to slow loss of walking ability in symptomatic pediatric patients with Batten disease.

Most recently, researchers have begun integrating artificial intelligence (AI) and machine learning (ML) technologies into diagnostic approaches for rare central nervous system (CNS) conditions. AI-based medical devices (AIMDs) are already being investigated in diagnosis, management, and pharmaceutical research for neurological diseases like brain tumors. ML algorithms have also demonstrated effectiveness in the diagnosis of systemic sclerosis as a result of being able to detect pulmonary involvement better than the standard diagnostic methods. With nearly 80% of rare disease being genetic, AI presents powerful opportunities for large-scale phenotypic and genetic analysis of existing databases and registries. Current research is underway to develop AI-driven computerized diagnosis support systems.

 

The Potential for Cross-Therapeutic Applications of Targeted Therapies  

Although rare disease research faces considerable financial, logistical, and technical obstacles, many emerging treatments in this therapeutic hold promise as potential treatments for populations beyond their initial target diseases. For example, patients with rare primary immunodeficiency diseases were the first to be cured by transplantation of allogeneic blood stem cells in the 1960s. Gene therapies are becoming more widespread across several types of diseases today, but their earliest successful studies were performed in patients with rare diseases, such as severe combined immunodeficiency syndromes, factor IX deficiency, and rare genetic diseases of the retina. These historical examples highlight the pioneering role of rare disease research on some of the most important discoveries made in clinical oncology, neurology, hematology, and more. Therefore, we can expect modern personalized medicine to be a driver of research collaborations between different medical specialties, each accelerating the pace of clinical breakthroughs for the other.  

 

Challenges and Opportunities 

Hurdles in Rare Disease Research 

Although a therapeutic focus on rare disease is a key clinical research trend expected for 2025, clinical development in this therapeutic area has historically been challenging for a variety of reasons. As with any clinical trial, patient recruitment remains a significant hurdle for sponsors and CROs, but especially for rare diseases, which have inherently small patient populations scattered across different geographical locations. Many of these diseases have only recently begun to be understood and do not yet have accurate diagnostic tools or treatment monitoring methods because identifying reliable biomarkers remains another major challenge.  

This lack of understanding of mechanisms underlying rare diseases also complicates clinical trial design because of the heterogeneity of disease presentation and the lack of standardized care protocols across different countries. These factors make it difficult for rare disease sponsors to establish consistent baseline measurements and control groups when using traditional trial designs. Furthermore, the limited market potential for diseases that occur only in a small subset of the general population, combined with the typical high costs of developing a new drug, often acts as a deterrent for pharmaceutical companies and investors. Securing long-term public funding is also challenging in rare disease research for similar reasons.  

Regulatory challenges add another layer of complexity, particularly when dealing with vulnerable populations such as children or individuals with rare progressive diseases. Randomized clinical trials (RCTs) are the gold standard trial design in medical research, but the large sample sizes required and traditional use of a placebo arm are not feasible when testing orphan drugs. In fact, the use of placebos in clinical trials raises significant ethical concerns, because many rare diseases are life-threatening conditions, wherein withholding potential treatment could have severe consequences for patients. Finally, despite gene editing technology playing an increasingly important role in treating several rare disorders, there are several complex ethical implications to consider. Visit this article from the US National Human Genome Research Institute to learn more about the ethical concerns of genome editing.  

 

Promising Solutions 

Despite these numerous challenges in rare disease research and clinical development, several promising solutions are emerging that may offer hope for patients going forward into 2025 and beyond. The most significant breakthrough has been the rapid rise of AI- and ML-powered technologies in both diagnostics and drug discovery for this therapeutic area. ML is capable of analyzing massive genetic and phenotypic patient datasets to identify potential therapeutic targets much faster than traditional screening by humans. Scaling these tools also enables researchers to pursue new biological studies and biomarker development.  

Next, gene therapy has made remarkable strides in several rare diseases, as discussed earlier in this article. Innovative approaches like CRISPR-Cas9 have made it possible to carry out precise genetic modifications that can potentially correct disease-causing mutations. Furthermore, the field of oncology is seeing a surge in novel cellular therapies, including stem cell treatments and chimeric antigen receptor (CAR) T-cell therapy, creating new therapeutic opportunities for previously untreatable rare cancers. 

Rare disease research has historically served as catalyst for significant advancements in life-saving medical treatments, which underscores the need for cross-specialty collaboration. Pursuing partnerships between researchers and clinicians from different fields results in the sharing of insights and methodologies that can accelerate treatment discovery by years. Today, there are several international rare disease research networks that emerged as crucial platforms for sharing resources, knowledge, and expertise worldwide. Patient registries and biobanks are also becoming widespread valuable resources for understanding disease progression and identifying potential therapeutic targets in this therapeutic area. 

 

The Future of Rare Disease Research 

As we approach Rare Disease Day 2025, the future of rare disease research holds considerable promise as advanced technology and collaborative research continues. Precision medicine provides the ability to analyze individual genetic profiles and disease mechanisms and this innovative approach to rare disease treatment is increasingly bridging long-standing gaps in the care of these underrepresented patients. With complex technologies like AI-driven analytics and gene editing tools, the field will likely continue to see a rapid evolution of therapeutic interventions as our understanding of these diseases increases. Partnerships between researchers, clinicians, and patient advocates are important in any therapeutic area, but it is especially crucial for successful clinical development in rare diseases because these patients often have very few options available to them following a diagnosis. Therefore, collaborations that combine clinical expertise with real-world patient experiences will ensure future developments remain focused on meaningful patient outcomes.  

 

Conclusion 

In conclusion, the upcoming Rare Disease Day 2025 commemorates the industry’s commitment to advancing research, funding, and innovation in the rare disease space. From patients and healthcare professionals to pharmaceutical companies and CROs, the scientific community must continue working together to overcome the unique challenges of rare disease research and drug development. Every breakthrough, no matter how small, represents renewed hope for patients and families affected by these conditions. This February 28, join TFS HealthScience and several organizations globally to take part in Rare Disease Day. By raising awareness, sharing knowledge, and fostering collaboration across borders and disciplines, we can accelerate the development of life-changing treatments for millions of patients worldwide. To learn more about how you can get involved, visit rarediseaseday.org.  

 

TFS HealthScience: Your Global CRO Partner in Rare Diseases 

TFS HealthScience Rare Diseases & Orphan Drugs CRO is dedicated to providing comprehensive services to support your oncology clinical trials. With a proven track record of over 70 rare disease clinical trials across multiple indications globally, we’re committed to delivering solutions that match your needs. Our global operations teams are fully experienced with navigating the complex landscape of orphan drugs clinical research, offering rigorous operational oversight and adherence to global standards. Visit our dedicated rare diseases CRO webpage to learn more or connect with a TFS representative here!