Patients and carers with lived experience of a disease have valuable insights to share with physicians and drug developers alike. This is especially true of rare diseases, defined in the US as those that affect fewer than 200,000 people nationwide and which collectively impact over 30 million Americans. For these unusual and uncommon disorders or conditions, real-life patient input can help make up for a lack of both clinician awareness and a history of strong data.

 

“Rare diseases are, by definition­­, uncommon,” explains Dr Jerry Vockley, director of the Center for Rare Disease Therapy and chief of the Division of Medical Genetics at UPMC Children’s Hospital of Pittsburgh. “Most frontline clinicians are managing full patient loads and seeing only the most common conditions. As a result, they might recognise a heart issue, an eye issue, or a neurological symptom, but not the underlying rare disorder that ties everything together. This is what sends many families into the classic “diagnostic odyssey,” which can last anywhere from a few days to as long as six years before they get an accurate diagnosis.”

The insights of individual patients living with rare conditions are, therefore, crucial to fostering a better understanding among treating physicians, informing better diagnostic and treatment choices. However, patient insights – represented collectively by a strong network of patient advocacy groups and associations – are also impacting the value chain far earlier, increasingly informing the research and development of new treatments.

 

Patient Associations: Raising the Collective Voice

Patient associations have long held a particularly important position in rare diseases. A combination of high R&D costs and low patient volumes led to a lack of private investment in rare diseases prior to the early 2010s. During this period, patient associations for rare diseases emerged worldwide to raise the voices of often-tiny patient populations and advocate for increased investment in drug development, an improved policy framework, as well as better diagnostics and care.

This was especially true in the US, as Michael Pearlmutter, CEO of the EveryLife Foundation, explains. “What differentiates the US from some countries that have wider, more holistic national rare diseases strategies is our tremendous innovation ecosystem,” he notes. “Much of the work done does not sit within the federal government. In many cases, it’s being driven by patient advocacy organisations and umbrella organisations like the EveryLife Foundation.”

Rare diseases now cost the US economy nearly USD one trillion annually, according to an EveryLife Foundation study, with indirect costs such as unpaid caregiver time and lost wages making up about 60 percent of the total. This suggests that patient associations are filling a massive public sector gap.

“Everyone in this space is working incredibly hard to keep patients at the centre, whether the focus is regulatory flexibility, policy reform, innovation, or development,” he adds. “But it’s also challenging. Resources are always tight, especially when nonprofits are carrying responsibilities that, in many countries, would fall to the public sector.” The EveryLife Foundation is attempting to move the dial through inter-stakeholder community building and guideline creation – including for ultra-rare conditions and patient-led drug development via bi-annual Scientific Workshops.

The landscape has, thankfully, moved on with rare diseases are higher on pharma’s agenda than ever before. Patent expiries for small molecule “mass market” blockbusters for conditions like cholesterol or blood pressure from 2011, combined with new capabilities in biologics and genomics, have led to an industry-wide pivot towards specialty medicines, including for rare diseases. In 2025, a full 57 percent of all novel drugs approved by the FDA were for rare (orphan) diseases.

However, even against a backdrop of increased investment in niche, high-cost, low-competition medicines for rare diseases, patient associations continue to play a pivotal role. They are advocating for and attempting to better channel rare disease investment, whether through public-private partnerships, venture philanthropy, or other means.

“One of the biggest shifts we’ve seen in the past two decades is that patients and advocates are increasingly stepping into leadership roles within their communities,” affirms Charlene Son Rigby, CEO of Global Genes, another rare disease patient advocacy group. “They’re often the ones who feel the urgency most, and they’re taking action.”

 

Case Study: The NIH Porphyria Consortium

On the institutional side, the USA’s gold-standard biomedical research institution – the National Institutes of Health (NIH) – has proven itself open to including patient input in certain rare disease research projects, with a few success stories already achieved.

“The NIH consortia provide a strong framework for building high-quality natural history studies, which are critical for drug development. One example is the NIH Porphyria Consortium, which received NIH funding over a 16-year period and brought together centres of expertise, clinicians from different specialties, patient advocacy groups, and industry partners,” lays out Dr Manisha Balwani, chief of the Division of Medical Genetics and Genomics at the Icahn School of Medicine at Mount Sinai, who was involved in the consortium.

“When that consortium started, there were no FDA-approved treatments for porphyria [a group of rare metabolic disorders],” adds Balwani. “Today, we are approaching a third FDA approval with another expected very soon.”

“That progress did not happen by chance. It was driven by the infrastructure that was built, the growth in disease understanding, and the active involvement of patient advocacy groups. Physicians within the consortium were also able to provide meaningful input into protocol design, helping identify what might work and what might not from a real-world clinical perspective. All of that accelerates drug development and ultimately benefits patients, which is incredibly rewarding to see firsthand.”

 

Patient-Focused Regulation?

The successes of NIH consortia, among others, are built on four decades of legislative progress, incentivising R&D and increasingly integrating patient input. Rare disease policy in the US has almost always been pushed forward by advocacy groups, dating back to the 1983 Orphan Drug Act, which was driven by a collective of patient activists that went on to found the National Organization for Rare Disorders (NORD). The ODA incentivises rare disease drug R&D through a seven-year period of market exclusivity for approved orphan indications and also grants tax credits of up to 25 percent (originally 50 percent) for clinical research costs.

Since then, the 1992 Prescription Drug User Fee Act (PDUFA) allowed the FDA to collect fees from drug sponsors to fund a faster review process, while the fifth reauthorisation of the PDUFA in 2012 created a Patient-Focused Drug Development (PFDD) program for the first time. Expanding on these bedrocks, the 21st Century Cures Act in 2016 mandated that the FDA include a “patient experience data statement” at the time of a drug’s approval, while also promoting the use of real-world evidence to support new indications for approved drugs.

Most recently, the FDA established a Rare Disease Innovation Hub in 2024, which the EveryLife Foundation’s Pearlmutter claims is “a great example of a success that we advocated for and eventually became a reality. Having a centre of excellence to ensure best practices are shared across CDER and CBER every time a rare disease product is reviewed is absolutely pivotal. It supports getting safe, effective treatments to patients as quickly as possible, which is what the entire community is striving for.”

“In rare disease development, patient experience should inform decision-making from the earliest stages, particularly where scientific understanding is limited and traditional clinical endpoints may not fully reflect meaningful benefit,” says Amy Comstock Rick, director of strategic coalitions at the FDA Rare Disease Innovation Hub.

“The FDA has long recognised this through its Patient-Focused Drug Development programme, which systematically captures patient and caregiver perspectives on symptoms, daily impact, and treatment priorities. This includes FDA-led public meetings, externally led meetings organised by patient groups, and patient listening sessions, with insights documented in publicly available “Voice of the Patient” reports that can inform both development planning and regulatory evaluation,” she adds.

 

Dialling in on Data

While a bolstered regulatory pathway for rare disease therapies is vital, without high-quality data, potential treatments will never find their way to patients. Patient groups have stepped up on this front, attempting to mine the wealth of data that exists and ultimately push drug development ahead.

As part of its efforts, Global Genes merged with the nonprofit data-sharing platform RARE-X in 2023. The initiative now supports data collection for more than 90 rare diseases, working with about 130 patient advocacy organisations.

“Patient advocates are increasingly building the tools and assets needed to move therapy development forward,” notes Son Rigby. “Many rare disease communities start with almost no structured data to describe their condition, and when data does exist, it’s often scattered across different academic labs or held within biopharma. The goal with RARE-X was to give patient communities a way to quickly set up high-quality, structured data collection that helps them understand their disease and move toward clinical trial readiness.”

Others, including the Undiagnosed Diseases Network Foundation, led by CEO Dr Danielle Carnival, are also getting involved. “One of the strengths of the UDNF is that participants are highly data-rich,” she notes.

“This creates an opportunity for UDNF to serve as a bridge between patients, researchers, and emerging discovery initiatives, including work focused on new models for therapy development and drug repurposing. As we grow, our role will increasingly be about connecting these efforts in a more deliberate way to help accelerate progress for people who currently have no clear treatment path.”

 

Not There Yet

While the policy and investment landscape for rare disease drug development in the US is stronger than ever, there is much work still to be done. Rare disease advocates will be hoping that the swingeing NIH funding cuts being carried out by the Trump administration do not affect ongoing research projects and, meanwhile, many rare disease patients are still living without diagnosis or treatment.

As the EveryLife Foundation’s Pearlmutter rues, “The truth is that 95 percent of rare disease patients in the US still don’t have an FDA-approved treatment. That is not what success looks like. While we are grateful for the existing innovation hubs, NCATS, and other federal entities that act as engines of hope, we also have to acknowledge the gaps.”

He, is, however, hopeful. “We are standing shoulder to shoulder with this community through every policy battle, every access challenge, and every effort to bring therapies to patients. We are inspired by the advocates who push us to do more, and we are committed to making sure they have every tool, resource, and ounce of support we can offer.”

Global Genes’ Son Rigby adds, “If we involve patients meaningfully, not just as participants but as partners, it will accelerate everything we’re all trying to accomplish. Whether you’re in biopharma, policy, research, or advocacy, we all have a responsibility to keep this at the forefront of our work.”