Rare Disease R&D: Continued Growth Amid Challenges

The rare disease market is expected to show a compound annual growth rate (CAGR) of 11.93% from 2025 to 2030.

The market for rare disease treatments continues to grow as pharma and biotech companies prioritize innovation in areas of high and unmet need amid advances in cell and gene therapies and precision medicine.

In 2024, 52% of the novel drugs approved by the US Food and Drug Administration (FDA) were for treating rare diseases. According to Mordor Intelligence, the rare disease market is expected to come in at $242.5 billion in 2025 and reach $426.03 billion by 2030, for a compound annual growth rate (CAGR) of 11.93% over the five-year period.

As part of their mission to get lifesaving treatments into the hands of patients who desperately need them, pharma and biotech companies continue to invest significantly in rare disease therapeutic areas. In addition to the burgeoning market opportunity, rare disease therapeutics often benefit from accelerated regulatory pathways, as well as the potential for market exclusivity for orphan indications. (Figures 1 and 2, which show the sustained growth in rare disease R&D, are taken from our upcoming Pharma R&D Annual Review 2025.)

Figure 1: Number of rare diseases being targeted by pharma

Source: Pharmaprojects, January 2025

Figure 2: Industry-sponsored rare disease trials by start date, 2010–present

Source: Trialtrove, January 2025

That is not to say that rare disease R&D is without its challenges. The number of patients with rare diseases is small, which can make it difficult to recruit and retain enough patients for a clinical trial. Plus, many of the diseases being studied have no existing treatments and thus no information or knowledge from previous studies to guide subsequent R&D efforts.

Matt Holms, Citeline VP, Sales – Patient Engagement & Recruitment, says that compared with more widespread conditions, rare disease R&D creates unique challenges in feasibility, site selection, and successful study recruitment due to extremely low prevalence within the general population.

“In many cases, few or no studies have ever been conducted in some of these conditions,” Holms says. “Furthermore, more protocols are being developed with a primary focus on personalized medicine, especially in oncology, where specific biomarkers or rare gene mutations are key inclusion criteria. Understanding where these potential patients exist, what sites to select, and ensuring enrollment are real challenges many sponsors are trying to solve for the first time within these rare diseases.”

According to David Wild, pharma/biotech reporter for In Vivo, rare diseases have lost a little bit of focus recently. “The rare disease landscape has seen significant shifts in the past year, with increased attention moving toward large population chronic diseases, particularly following the success of GLP-1 agonists and expanding markets for cardiometabolic treatments,” he says.

“In the US, the rare disease community faces several critical challenges, including uncertainty around federal funding for clinical trials and academic research, potential changes in healthcare policy, and questions about Medicare reimbursement for high-cost rare disease therapies, particularly innovative cell and gene therapies,” he says. “These factors collectively impact both research momentum and patient access to treatments.”

“In the EU, changes in the regulatory data protection for orphan drugs could be a challenge for developers of rare disease therapies over coming years,” says Eliza Slawther, senior writer for Pink Sheet. “Meanwhile in the US, political changes also threaten to freeze funding for the development of medicines for rare diseases.”

Still, the future for rare disease R&D remains promising amid the industry’s technological advances and continued emphasis on centering the patient in all efforts. “Rare disease clinical research studies are continually expanding and offer hope to many impacted by debilitating conditions,” Holms says.

Slawther notes there are a growing number of initiatives aimed at improving the rare disease landscape globally. “For example, the European Medicines Agency has been working closely with the FDA to actively agree on common endpoints for some rare diseases, which will help drugmakers generate evidence that is acceptable to regulators in different parts of the world,” she says.

Tough road to enrollment

One of the most challenging aspects of rare disease R&D is patient recruitment and retention. Because the protocols for rare disease clinical trials are so complex, and the number of candidates is small to begin with, it can be extremely difficult to locate patients who fit all the criteria.

“Sponsors of rare disease trials face unique challenges that require close collaboration with patient advocacy groups and academic centers to achieve adequate enrollment,” Wild says.

“The pool of patients is significantly smaller for rare disease trials, so finding participants is challenging,” Slawther says. “In addition to this, rare diseases are often highly variable in terms of their presentation between patients, which poses challenges in terms of deciding which patients are suitable for a study.”

“The geographic dispersion of rare disease patients poses a particular challenge, especially in rural areas and regions with less-developed healthcare infrastructure,” Wild says. “Patient identification can be labor-intensive and time-consuming, often leading to extended recruitment periods. Despite these challenges, this meticulous work remains essential for addressing critical unmet patient needs and advancing treatment options for rare diseases.”

A new recruitment era?

As Slawther notes, the industry continues to work with regulators and patient networks to find ways around rare disease recruitment challenges. To expand their pool of candidates, companies conducting rare disease R&D often reach out to patient advocacy groups for the rare disease in question as well as organizations such as the National Organization for Rare Disorders (NORD) and Rare Patient Voice. There are also rare disease patient registries that collect genetic and clinical data about individuals with rare conditions.

“Clinical research is an integral step in developing medical advances to improve lives, and patient participation is a particularly key part of the process,” says Laura Mullen, Director of Marketing and Communications, Rare Patient Voice. “Rare disease patients play a vital role in clinical trials, but due to small populations, medical challenges, and other factors, recruitment can be challenging. At Rare Patient Voice … we are proud to specialize in connecting people living with rare diseases with opportunities to take part in research.”

Employing decentralized trials in which patients can be monitored at home via various wearable and portable technologies is another way in which the industry is broadening patient candidate reach.

“Decentralized clinical trials are becoming more popular, and these will play a huge role in both recruiting and retaining trial participants going forward,” Slawther says. “If companies can run studies that do not require patients to travel long distances, they will be able to recruit patients who otherwise would have been left out of the study due to logistical or financial limitations.”

“The widespread adoption of decentralized and digital clinical trials, accelerated by the COVID-19 pandemic, has transformed patient recruitment and retention strategies,” Wild says. “Wearable devices and tablets have become valuable tools for streamlining recruitment, monitoring treatment effects and supporting medication adherence. These technologies are particularly beneficial for rare disease patients who may live far from traditional research centers, reducing the burden of trial participation.

“Enhanced treatment adherence through these digital tools not only increases the likelihood of clinical benefit but also strengthens patient retention throughout the study duration,” Wild adds.

“I’m looking forward to seeing how companies can begin to design trials for new medicines in ways that are more inclusive,” Slawther says. “With many countries now releasing guidance on decentralized trial designs, the time is now for companies to engage with regulators and make these innovative studies a reality. This will potentially mean that patients from across the globe can join a study without needing to leave their jobs, family and home country behind.”

When it comes to feasibility and site selection, Holms says, “the traditional approach of going to a CRO that has experience in each rare disease often doesn’t apply,” and sponsors may be better served by data-focused partners with complex proprietary and real-world data (RWD) assets.

“More specifically, visibility into data at the site and patient levels is critical to the foundation of selecting the right sites versus traditional approaches of replicating what’s been done before with sites,” he says. “Once sites are selected, depending on the sites alone is often not enough to meet enrollment goals. Moreover, traditional direct-to-patient recruitment solutions [i.e., advertising] focused on finding patients not known to the sites have a poor track record in rare disease…. Newer, different recruitment approaches with data as the foundation are now emerging to better identify potential rare disease patients who ‘match’ a majority of the protocol’s criteria by leveraging big data.”

Future driven by technology

There is no doubt the rare disease space faces some immediate challenges. But its immense promise will continue to draw R&D investment from pharma and biotech companies.

“While the cell and gene therapy space has faced both technical challenges and some clinical setbacks, these technologies continue to hold tremendous potential for rare disease patients,” Wild says. “As manufacturers refine their approaches and develop more cost-effective production methods, these groundbreaking treatments will become more accessible.

“Additionally, artificial intelligence [AI] is being strategically integrated across the industry, from drug discovery to clinical trial design. While we're still in the early stages of understanding AI's full potential in rare disease research and treatment, its application promises to accelerate innovation and improve patient outcomes once the most effective use cases are identified and implemented.”

“A variety of newer treatment innovations [i.e., mRNA, gene therapy, CRISPR] combined with enhanced personalized medicine approaches will continue to provide innovation within rare disease research,” Holms says.

“Citeline wants to provide more access and efficiencies — for both patients exploring clinical trial opportunities and sponsors looking for patients within rare disease,” he adds. “Innovating on how our data and services will ensure more effective planning, patient access, site selection and data-focused recruitment strategies will ensure these patients continue to have hope to improve the quality of their lives and sponsors see success to continue investing in rare disease research.”