Defying the odds: How data and cell & gene therapy are rewriting the rare disease story

Rare diseases, affect a small percentage of the population, but their collective impact is profound. The United States defines a rare disease as one affecting fewer than 200,000 individuals, while the European Union classifies it as a condition impacting fewer than 1 in 2,000 people (1,2). Despite their rarity, these diseases affect an estimated 263 to 446 million people globally, with approximately 80 per cent having a genetic basis. Most lack effective treatments, making innovation in precision medicine crucial (3-5).

While numerous rare diseases exist, some are more frequently diagnosed than others. Cystic fibrosis is a hereditary condition affecting the lungs and digestive system and is found most often in people of European ancestry. Duchenne muscular dystrophy is a severe, progressive form of muscular dystrophy that primarily affects males. Hemophilia is a genetic disorder characterised by improper blood clotting, leading to excessive bleeding. Both Gaucher disease and Fabry disease stem from enzyme deficiencies that cause fatty substances to accumulate in various body tissues.

The role of cell and gene therapies in rare diseases

Recent breakthroughs in cell and gene therapies are reshaping the landscape of rare disease treatment. These advanced therapeutic modalities target the underlying genetic causes, offering potential one-time treatments that contrast sharply with traditional therapies requiring lifelong management.

Gene therapy: Redefining treatment paradigms

Gene therapy is transforming treatment paradigms by modifying, replacing, or repairing defective genes, making it particularly effective for monogenic disorders. It employs two primary delivery approaches: in vivo, where therapeutic genes are directly delivered into a patient’s cells using viral or non-viral vectors, and ex vivo, where cells are extracted, genetically modified outside the body, and then reintroduced—an approach commonly used for hematologic disorders.

Examples of approved gene therapies:

• Luxturna: The first FDA-approved in vivo gene therapy for a rare retinal disorder, restoring vision in patients with biallelic RPE65 mutation-associated retinal dystrophy.
• Zolgensma: A breakthrough gene therapy for spinal muscular atrophy (SMA), significantly improving motor function with a single infusion.

Cell therapy is a revolutionary approach that involves transplanting live cells to repair or replace damaged tissues. Key advancements include stem cell therapy, where induced pluripotent stem cells (iPSCs) offer regenerative potential by correcting genetic mutations before transplantation, and CAR T-cell therapy, a form of immunotherapy that genetically modifies T-cells to better identify and attack diseased cells. Both of these are showing promising results in rare cancers.

Harnessing real-world data for rare disease research

Real-world data (RWD) is critical in accelerating rare disease treatment by informing clinical trial design, regulatory decision-making, and post-marketing surveillance (6).

Key applications of RWD:

• Understanding disease progression: RWD helps characterise natural disease history, symptom severity, and treatment needs. For instance, it was instrumental in securing Zolgensma’s approval by demonstrating its real-world impact on SMA patients.
• Supporting health technology assessments (HTA): RWD informs regulatory decisions by providing real-world evidence of therapy effectiveness. For example, the approval of Cerliponase alfa for Batten disease leveraged historical data when large-scale trials were unavailable (7).
• Enhancing post-marketing surveillance: Ongoing monitoring of gene therapies like Luxturna ensures long-term safety and efficacy insights beyond clinical trials.

Overcoming barriers to accessing gene therapies

Despite their promise, cell and gene therapies face significant adoption challenges, including high costs, infrastructure limitations, and regulatory hurdles.

Potential solutions:

• Strengthening early diagnosis infrastructure: Expanding newborn screening programs and diagnostic capabilities can ensure timely intervention.
• Developing value-based pricing models: Innovative reimbursement structures, such as outcomes-based agreements, can enhance affordability.
• Building centers of excellence: Establishing specialised hubs for gene therapy delivery can streamline patient access and treatment administration.

Case study: Leveraging AI and data science for rare disease research

In a recent study on congenital thrombotic thrombocytopenic purpura (cTTP), Axtria integrated lab data with claims records to identify clinical and economic outcomes for patients without a formal diagnosis code (8).

The future of precision medicine in rare diseases

With rapid advancements in gene-editing technologies like CRISPR, next-generation sequencing, and AI-powered analytics, the future of rare disease treatment is becoming increasingly personalised and effective. While barriers to widespread adoption persist, continued collaboration between researchers, healthcare providers, and policymakers will be key to unlocking the full potential of these transformative therapies. The future of rare disease care is here- driven by technology, shaped by innovation, and powered by hope.

References

1. Rare diseases at FDA. United States Food and Drug Administration. Accessed January 14, 2025.  https://www.fda.gov/patients/rare-diseases-fda 
2. Medical products for rare diseases and conditions. United States Food and Drug Administration. Accessed February 26, 2024. https://www.fda.gov/industry/medical-products-rare-diseases-and-conditions 
3. Rare diseases at the European Commission. Accessed January 14, 2025. Rare diseases – European Commission
4. Chung CCY; Hong Kong Genome Project; Chu ATW, Chung BHY. Rare disease emerging as a global public health priority. Front Public Health. 2022 Oct 18;10:1028545. doi: 10.3389/fpubh.2022.1028545. PMID: 36339196; PMCID: PMC9632971.
5. Nguengang Wakap, S., Lambert, D.M., Olry, A. et al. Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database. Eur J Hum Genet 28, 165–173 (2020). https://doi.org/10.1038/s41431-019-0508-0
6. Liu J, Barrett JS, Leonardi ET, Lee L, Roychoudhury S, Chen Y, Trifillis P. Natural History and Real-World Data in Rare Diseases: Applications, Limitations, and Future Perspectives. J Clin Pharmacol. 2022 Dec;62 Suppl 2(Suppl 2):S38-S55. doi: 10.1002/jcph.2134. PMID: 36461748; PMCID: PMC10107901.
7. Dayer VW, Drummond MF, Dabbous O, Toumi M, Neumann P, Tunis S, Teich N, Saleh S, Persson U, von der Schulenburg JG, Malone DC, Salimullah T, Sullivan SD. Real-world evidence for coverage determination of treatments for rare diseases. Orphanet J Rare Dis. 2024 Feb 7;19(1):47. doi: 10.1186/s13023-024-03041-z. PMID: 38326894; PMCID: PMC10848432.
8. Shaikh, J. (2025) Cell & Gene Therapies for rare diseases: The power of RWD, Cell & Gene Therapies for Rare Diseases: The Power of RWD. Available at: https://insights.axtria.com/blog/cell-and-gene-therapies-for-rare-diseases-unlocking-new-possibilities-with-real-world-data#:~:text=Cell%20and%20gene%20therapies%20hold%20significant%20promise%20for,many%20patients%20suffering%20from%20conditions%20previously%20deemed%20untreatable. (Accessed: 19 February 2025).