Rare Disease Day is an observance held on the last day of February annually to raise awareness for rare diseases and improve access to treatment and medical representation for individuals with rare diseases and their families. To mark Rare Disease Day 2025, DDW gathered insight from a range of industry experts.

How has the landscape for rare disease drug development evolved in recent years?

Jim Wilson, President and CEO of GEMMAbio

So much scientific progress has been made in recent years, and two things that stand out as major factors in the changing landscape are decreased funding and increased patient advocacy. The rarity of these diseases often means that they don’t attract the same level of research funding as conditions that are more commonly diagnosed. On the other hand, rare diseases have an incredibly close-knit, global community of supporters who have made amazing strides in expanding awareness.

Gerard Caelles, Chief Business Officer at SpliceBio

The landscape of rare disease drug development has changed significantly in recent years, primarily due to advances in genetic research, next-generation sequencing, and the emergence of new therapeutic modalities. Historically, progress was limited by scientific and technological barriers, including limited understanding of disease mechanisms, challenges in identifying viable drug targets, difficulties in achieving precise and efficient delivery to affected tissues, and the complexities of manufacturing these advanced therapies at scale. The past decade has seen major breakthroughs that have made it possible to develop treatments that were previously out of reach.

A clear example of this shift is spinal muscular atrophy (SMA), a disease that, until recently, had no effective treatments. Today, patients have multiple options spanning different modalities: Spinraza (antisense oligonucleotide therapy), Zolgensma (AAV-based gene therapy), and Evrysdi (small molecule splicing modifier). This success story reflects how drug development for rare diseases has evolved—from symptom management to the development of multiple drugs that target the underlying genetic cause.

Jordi Fabrega, CEO of CONNECTA Therapeutics

The landscape for rare disease drug development has undergone a significant transformation over recent years, driven by the increasing collaboration between academia, biomedical research companies, regulatory bodies and patient advocacy groups.

This trend, which has been particularly dynamic in the CNS field, has led to the recent introduction of new treatments for life threatening diseases such as amyotrophic lateral sclerosis (ALS), and major advances in neurodevelopment disorders research like in Rett syndrome or Fragile X syndrome, where early intervention is crucial for affected individuals and their families.

What impact have new technologies, such as gene therapies and gene editing, had on patients?

Jim Wilson

When these therapies have been evaluated in the clinic, the impact on the quality of life for patients has been dramatic. Unfortunately, the recent erosion in financial support for these technologies will limit the overall impact beyond what is currently available.

Gerard Caelles

Gene therapies and gene editing technologies have fundamentally changed the treatment paradigm for rare diseases, offering the potential for long-term – and in some cases – curative outcomes, rather than chronic symptom management. For many patients who previously had no viable treatment options, these advances have provided hope and, in some cases, dramatically improved quality of life. For the first time, patients with previously untreatable diseases now have access to therapies that directly target the root genetic cause of their condition. This progress spans a wide range of indications, including haematological disorders, neurological diseases, and genetic forms of blindness and hearing loss. As research continues to refine these technologies, gene therapies are poised to transform even more diseases, further expanding the scope of precision medicine and potentially opening the door to treatments for more prevalent conditions.

Josep Prous, CSO of CONNECTA Therapeutics

The rise of advanced therapies – including gene therapies, the use of induced pluripotent stem cell (iPSC) technologies to develop patient-derived models of rare neurological diseases, and the application of artificial intelligence in target identification and biomarker discovery – is revolutionising the approach to previously untreatable neurological conditions, with demonstrated successful applications in diseases such as spinal muscular atrophy (SMA) and Duchenne muscular dystrophy (DMD).

However, despite their promise, advanced therapies also present challenges – including concerns about long-term safety and durability and the high cost of development and treatment. Costs can reach millions per patient, raising issues regarding reimbursement, insurance coverage and equitable access, and limiting the widespread availability of these life-changing treatments.

How have improved methods of diagnosis, using techniques such as next generation sequencing, improved the outlook for rare disease patients?

Jim Wilson

Genetic diagnosis has been incredibly helpful in reducing the investigative odyssey necessary for access to genetic medicines. A broader application of genetic sequencing in large populations or in newborns could have an even greater impact, leading to a more optimistic outlook for rare disease patients and their families.

Gerard Caelles

Next-generation sequencing (NGS) has been a game-changer, significantly reducing the diagnostic journey that many rare disease patients face. By enabling earlier and more accurate diagnoses, NGS allows for timely intervention, including access to targeted treatments and enrolment in clinical trials for emerging therapies such as gene therapies.

Beyond individual diagnoses, advances in genomic testing have also transformed clinical trial recruitment and drug development. By rapidly identifying patients with specific genetic mutations, these technologies help match individuals to relevant clinical studies more efficiently, accelerating the pace of research and bringing therapies to market faster. Additionally, broader adoption of genomic screening has expanded the pool of eligible patients, making trials more robust and generating higher-quality data that supports regulatory approval.

Jim Wilson

As these technologies continue to evolve, they are not only improving patient outcomes but also driving innovation across the rare disease space.

Josep Prous

Since the advent of next-generation sequencing (NGS) we have observed a dramatic improvement in the ability to identify rare diseases, significantly reducing the time from symptom onset to diagnosis and potential therapeutic intervention.

Additionally, in the field of neurosciences, the rapid evolution and adoption of imaging biomarkers has provided clinicians with invaluable tools to elaborate the most appropriate strategy for patient care.

Giusy Di Conza, Head of Research at iOnctura

In rare cancers, a whole host of different technologies have converged to make diagnosis faster and more accurate. It’s now common to sequence the genome of a cancer to see which mutations are present, and therefore which drugs and therapies are most appropriate. Getting this information in a timely manner allows doctors to make the right decisions quickly, giving patients better outcomes and ultimately better chances of survival.

What are the biggest challenges facing developers of rare disease therapies in the coming years?

Jim Wilson

The science of rare disease product development continues to advance at a breathtaking rate. The potential to substantially change the trajectory of rare diseases that is now possible, was like science fiction just a few years ago. The challenge, though, is how to deploy this technology across a broad range of diseases – which are viewed individually as too rare to justify the necessary investment.

Gerard Caelles

The development of rare disease therapies faces several challenges across research, clinical development, manufacturing and commercialisation.

On the scientific and research side, one of the most pressing challenges remains delivery, delivery, delivery – ensuring that therapies reach the right tissues effectively. This is particularly critical for gene therapies, where current viral vectors are limited by cargo capacity and tissue specificity.

On the clinical development side, rare diseases present unique hurdles, particularly in patient identification and clinical trial design. With small and geographically-dispersed patient populations, enrolling sufficient numbers for traditional clinical trials can be difficult. Moreover, many rare diseases lack natural history data, making it harder to define meaningful clinical endpoints and demonstrate treatment efficacy. Patient advocacy groups play a vital role in bridging these gaps. Organisations like the Foundation Fighting Blindness have been instrumental in identifying patient populations, supporting genetic testing initiatives, and running natural history studies (such as ProgStar in Stargardt disease) to inform trial design and regulatory approvals. Inspired by this work, we launched POLARIS, the first industry-sponsored natural history study in Stargardt disease, which is proving essential in expediting trial enrollment and improving our understanding of disease progression.

On the manufacturing side, producing complex biologics at scale – particularly gene therapies for systemic indications – remains a major challenge. The industry still faces bottlenecks in vector production, yield optimisation, and cost efficiency, all of which impact the of bringing these therapies to patients and their affordability. Advances in process development, automation, and improved vector engineering are gradually addressing these limitations.

On the commercial side, pricing and reimbursement continue to be major barriers to patient access. The high development and manufacturing costs of gene therapies, coupled with their potential one-time curative nature, challenge traditional pricing structures that were designed for chronic therapies. Healthcare systems and payers are still adapting to this shift, with outcome-based reimbursement models and innovative financing mechanisms emerging as potential solutions. However, ensuring that these therapies are accessible to patients while maintaining incentives for continued innovation requires close collaboration between payers, regulators, developers, and patient advocacy groups to establish long-term funding models.

Jordi Fabrega

Developing new drugs for rare diseases will remain a challenging task, requiring strong commitment from key stakeholders, particularly biopharmaceutical industry and policy makers, and their willingness to in-license and streamline the reimbursement landscape surrounding the introduction of innovative treatments.

Moreover, the small patient populations inherent to rare diseases, leading to longer recruitment periods and extended clinical trials, may be further amplified in certain areas, such in rare neurodevelopmental disorders (such as Rett, Fragile X, Angelman, Di George, etc), where the diverse manifestations and degree of severity, combined with the concomitant use of symptomatic medications, add further complexities to the development and approval of new treatments.

What opportunities do you see in the coming years for rare disease drugs?

Jim Wilson

The road ahead is long, but there is hope! One of the greatest areas of opportunity in the years ahead is for increased collaboration among the many players in the industry – including governments, healthcare providers, patient advocacy groups, pharmaceutical companies and biotech firms. We are working to address this by creating an international coalition to simplify and coordinate review and approvals.

Gerard Caelles

The coming years present significant opportunities for rare disease drug development, driven by advances in next-generation gene therapies, improvements in sequencing and diagnostics, expanded regulatory pathways, and novel funding models that support patient access.

One of the most impactful areas of progress is in next-generation gene therapies, particularly in overcoming two of the field’s biggest challenges: packaging capacity and tissue tropism. Many rare diseases are caused by mutations in large genes that exceed the natural packaging limit of AAV vectors, restricting the scope of gene therapy applications.

At the same time, improvements in sequencing technologies and genetic diagnostics are accelerating patient identification and clinical trial recruitment. Advances in whole-genome sequencing, newborn screening programs, and AI-driven variant interpretation are enabling earlier and more precise diagnoses, allowing patients to access treatments or participate in clinical trials sooner. These innovations are also enhancing drug development efficiency, ensuring that trials enrol the right patients faster and generate high-quality data to support regulatory approval.

Regulatory agencies are also playing a crucial role in shaping the future of rare disease therapies. Expanded regulatory pathways, including accelerated approval programs, greater use of real-world evidence, and biomarker-driven trial designs, are facilitating the development and approval of new treatments. The increasing adoption of adaptive trial designs is further streamlining drug development, reducing timelines while maintaining rigorous safety and efficacy standards.

Beyond scientific and regulatory advancements, new funding and reimbursement models will be essential in ensuring patient access. Outcome-based reimbursement models, innovative financing mechanisms, and closer collaboration between payers and manufacturers are emerging to help balance affordability with continued innovation.

Jordi Fabrega

With up to 95% of rare diseases still lacking a cure, the sector is poised for unprecedented growth, with the coming years likely to bring continued breakthroughs driven by personalised medicine and novel therapeutic modalities.

From an industry perspective, the commitment of pharmaceutical companies to nurturing their pipelines with innovative assets for underserved populations, coupled with the increasing availability of public and private funding, should facilitate the emergence of new biotech companies specialised in rare diseases treatments.

Giusy Di Conza

As diagnosis techniques become faster and more accurate, and as our scientific knowledge behind neglected, rare and hard-to-treat cancers improves, we will be able to produce more personalised therapies. This means that we are creating and providing patients with targeted, precise therapies, which specifically target their disease, with fewer side effects. It’s a huge opportunity to improve the health span of patients, with more precision medicine.

Biographies

Having started his work in gene therapy nearly 40 years ago, Jim Wilson is the President and CEO of GEMMA Biotherapeutics (GEMMABio), a company developing advanced rare disease therapies. He was recruited to the University of Pennsylvania in 1993 and created the first and largest academic-based programme in gene therapy. He has also been active in facilitating the commercial development of new gene therapy platforms through the establishment of eight biotechnology companies. Wilson’s research has been focused on rare inherited diseases, and on addressing unmet needs for patients in marginalised populations.

Gerard Caelles joined SpliceBio in 2016 as the responsible for Business Development operations. Prior to SpliceBio, Caelles served as the Business Development Manager at Bionure, where he was focused on business development and partnering around the company’s novel candidate in the orphan neuro-ophthalmology space, as well as on fundraising efforts.

Jordi Fàbrega has held various positions in the pharmaceutical industry and has several years of consultancy experience in the Pharma and Med Tech sectors. Prior to joining Connecta, Fàbrega was Director of Business Development at Biocat. He has broad experience in strategy, business development, marketing, market access and regulatory.

Joseph Prous Jr is Vice President of R&D at Prous Institute for Biomedical Research and Strategic Advisor to life sciences organisations, where he is responsible for the design and implementation of in silico drug discovery and safety technologies. He was previously Vice President and Chief Scientific Officer of the Healthcare and Science business of Thomson Reuters, following the acquisition of his former company Prous Science by Thomson Scientific. He has longstanding experience in establishing collaborations with biomedical research organisations.

Giusy Di Conza holds a PhD in endocrinological cancers. She joined iOnctura as Head of Research in 2022 with over 12 years of experience in onco-immunology and tumour-stroma interactions. During her career, Di Conza has furthered understanding of the molecular and biological interactions that occur within the tumour microenvironment, has uncovered novel preclinical targets, and published over 30 research articles. Read Di Conza’s DDW Meet the Researcher.