For decades, the story of rare disease research ran in one direction. Patients waited, researchers studied, therapies slowly arrived. People with conditions like IgA nephropathy, Duchenne muscular dystrophy, or spinal muscular atrophy joined clinical trials because trials were effectively the only way to access anything that might help.
That story is changing. Approved treatments are now reaching patients across a growing number of rare diseases. At the same time, something unexpected is happening: enrollment in the trials that would bring the next generation of therapies is slowing down in the United States.
This is a paradox most patients can sense without being able to name. It is also quietly reshaping how drug companies plan studies, which countries see new trials first, and how long patients will wait for the treatments that come after the ones that exist today.
When the only option becomes one of five
Consider IgA nephropathy, a progressive kidney disease that causes roughly 1 in 3 patients to reach kidney failure within 20 years of diagnosis. As recently as 2021, there was no FDA-approved therapy targeted to the disease itself. Standard of care involved blood pressure medication and, in advanced cases, dialysis or transplant.
In the four years since, 5 therapies have received FDA approval for IgA nephropathy (HCPLive, 2025): Tarpeyo (budesonide) in December 2021, Filspari (sparsentan) in February 2023, Fabhalta (iptacopan) in August 2024, Vanrafia (atrasentan) in April 2025, and Voyxact (sibeprenlimab) in November 2025.
The same pattern is playing out in other rare disease communities. Spinal muscular atrophy had zero approved therapies before Spinraza in 2016 and now has 5, including Zolgensma, Evrysdi, the spinal gene therapy Itvisma, and the add-on Isembyld. Duchenne has moved from no approved disease-modifying drugs to a growing roster of exon-skipping therapies and a gene therapy. Sickle cell, Pompe, and Fabry have all seen their treatment options transformed across a single decade.
A patient weighing whether to join a trial today is doing different math than a patient weighing the same question in 2019. The question used to be: do I accept unknown risk to access a potential therapy, given that no other targeted option exists? The question now is: do I accept unknown risk, plus the possibility of randomization to placebo, when I could instead get a proven drug filled at my pharmacy?
Why rare disease clinical trials are moving overseas
The enrollment effect is not uniform across countries. Therapies approved in the US are often not yet approved or reimbursed in Europe, parts of Asia, or Latin America. Patients in those regions face the same calculus US patients faced 5 years ago: join a trial or accept that no targeted option exists.
Sponsors have noticed. Trial site distribution for late-stage rare disease studies is shifting toward ex-US locations, particularly Eastern Europe, China, Japan, South Korea, and parts of Latin America. ICON, one of the largest clinical research organizations supporting rare disease research, operates 97 offices across 55 countries and reports having supported 779 rare disease studies, enrolling more than 24,000 patients across 6,200 sites worldwide (Precision for Medicine, 2025).
This is rational from a sponsor's perspective. Trials need to recruit on schedule or they collapse. More than 80% of clinical trials fail to enroll on time, and roughly 55% of trials worldwide fail outright due to insufficient enrollment (Applied Clinical Trials Online, 2022). A failed Phase 3 means a multi-year program writes down hundreds of millions of dollars.
The cost of that rational response falls on different patient communities in different ways. US patients gain faster access to newly approved treatments. US trial sites see less new investment, which over time means fewer research-active centers, fewer experienced investigators, and fewer pathways for patients whose approved drugs are not enough. International patients enroll into studies of therapies their health systems may not fund for years after US approval.
Why the slowdown shapes the next decade
Trials that cannot enroll do not generate the data needed for approval. A cross-sectional analysis of 659 rare disease trials registered with ClinicalTrials.gov found that 30% were discontinued before completion and another 31.5% remained unpublished four years after completion, meaning the majority of rare disease studies produce no publicly available result (Bourgeois et al., PLOS Medicine, 2019). Separately, Tufts Center for the Study of Drug Development has documented that rare disease Phase 2 and Phase 3 protocols involve longer study initiation periods, longer follow-up durations, and more planned patient visits than non-rare studies, all of which compound the difficulty of enrolling and retaining patients (Getz et al., Therapeutic Innovation & Regulatory Science, 2022).
Each of those extensions is expensive. A trial that cannot fill its US sites either drops them, runs longer than planned, or reduces endpoints to salvage the analysis. A therapy that would have been ready in 2029 becomes the therapy that launches in 2032, if it launches at all.
The drugs delayed or shelved in this window are the drugs meant to close the gaps the current generation of approvals still leaves. In IgA nephropathy, that means the patients whose proteinuria is not controlled by the current therapies, the patients who progress despite treatment, and the future patients who would benefit from earlier or more disease-modifying approaches.
“Probably only 10% to 20% of ALS patients are eligible to participate in clinical trials.”
NeurologyLive, summarizing Neurology 2019 eligibility analysis
A harder decision, not a simpler one
Patients asking whether to join a trial today deserve respect for whatever they decide. A patient with good insurance and an approved drug that works well may reasonably prioritize the therapy that exists now. A patient whose approved drug is not controlling the disease may reasonably pursue a trial that could reach the next mechanism. Both decisions are rational. Neither is obligated.
Several groups of patients still have clear reasons to enroll even when approved treatments exist.
Patients whose response to approved therapy is incomplete
In IgA nephropathy, proteinuria reduction from the approved mechanisms varies patient to patient. For some it is not enough. Trials of next-generation complement inhibitors and B-cell modulators are actively recruiting, and eligible patients often qualify specifically because first-line drugs fell short.
Patients with aggressive or progressive disease
When the realistic timeline of kidney decline, muscle loss, or neurological progression is 5 to 10 years rather than 20, waiting for a 2030 approval is not a viable plan. Trial participation is often the most practical way to access tomorrow's therapy today.
Patients outside the US
In Europe, much of Asia, and most of Latin America, the newest US-approved drugs may not be reimbursed for years. Trial enrollment remains the primary route to those therapies for international patients.
Patients who want their data to count
Rare disease drug development cannot advance without patient participation. A person who enrolls contributes directly to whether 2030 treatments reach 2030 patients. Community impact is a legitimate reason to volunteer even when personal necessity is lower than it used to be.
How to think about your own position
The practical question for most rare disease patients is not whether trial enrollment is slowing down nationally. It is whether any individual trial would be a reasonable fit for them given current options.
A workable frame: start with whether approved drugs exist for your condition. If they do not, trials remain the primary avenue to any targeted therapy. If approved drugs do exist, ask how well they are working for you specifically. Adequate response usually means trials are optional. Inadequate response means the question becomes more pressing, and trial participation may be the fastest route to the next mechanism.
Risk tolerance, geography, financial resources, and current health status all shape the answer. A patient in a rural area with a young family weighs these factors differently than a retired patient in a trial-rich city. Neither decision is more virtuous than the other.
What is true across both decisions: the patient community benefits when the people who do want to participate can find the right trials quickly. That part of the system is fixable.
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Frequently asked questions
Should I join a clinical trial if an approved drug already exists for my condition?
It depends on how well the approved drug is working for you. If your disease is well-controlled on an approved therapy, a trial is usually optional and you are not obligated to join. If the approved drug is not controlling your disease, or your progression is faster than the approval timeline for next-generation therapies, a trial is often the fastest route to a newer mechanism. The decision is individual and should be made with your specialist.
What is the risk of being randomized to placebo in a rare disease clinical trial?
Randomization ratios vary by trial. Many rare disease Phase 3 studies use 1:1 randomization, meaning a 50% chance of placebo. Others use 2:1 or 3:1 ratios that favor active drug. Most modern rare disease trials include open-label extensions that give all participants access to active drug after the blinded period ends. Ask the research coordinator for the specific randomization ratio and crossover policy before enrolling.
Can I stay on my approved treatment while participating in a clinical trial?
Sometimes yes, sometimes no. Some trials require a washout period off current therapy. Others allow participants to continue background treatment and test the investigational drug as an add-on. Eligibility criteria spell this out directly. If staying on your current drug matters to you, ask about this during screening rather than after enrollment.
Why are rare disease trials moving to Europe, Asia, and Latin America?
Sponsors go where eligible patients are concentrated and where enrollment will close on time. In countries where newly FDA-approved drugs are not yet reimbursed, patients still face the choice US patients faced 5 years ago: join a trial or accept that no targeted option exists. Those regions now see faster enrollment for late-stage rare disease studies, which is why major clinical research organizations operate hundreds of sites across dozens of ex-US countries.
How do I find a clinical trial for my specific rare disease?
Start with the disease page on Trial Friend for your condition, which shows active trials, approved treatments, and the drug mechanisms being tested. ClinicalTrials.gov lists every registered study but is harder to filter. Patient advocacy foundations for your specific condition often maintain curated lists of the trials they know well. Your treating specialist is the best source for whether any given trial makes sense for your specific case.
How Trial Friend can help
Trial Friend exists to close the gap between patients who are open to participating and the trials they might be eligible for. Our disease pages show current FDA-approved treatments, active trials, and the drug mechanisms being tested in each one. Our trial matching tool lets you describe your situation once and see relevant options. Our drug pages let you compare approved therapies with what is still in development.
For patients whose current treatment is not delivering what they need, this information is directly actionable. For patients considering whether to step into a trial despite a proven drug existing, it provides the data required to have a real conversation with a specialist.
The slowdown in rare disease trial enrollment is not a problem individual patients caused, and it is not a problem individual patients are obligated to solve. It is a system-level issue in how drug development works once effective therapies start to exist. Seeing it clearly is how patients make the decision that is right for them, whatever that decision turns out to be.