Update from the Huntington’s Disease Society of America (HDSA)
Date: March 5, 2026
The Huntington’s disease (HD) community currently has no approved disease-modifying therapies. While existing treatments may help manage certain symptoms, they do not stop or slow the underlying biological progression of the disease. For families living with this terminal, neurodegenerative condition, the search for a treatment that can alter the course of the illness is an urgent necessity.
The Importance of ENROLL-HD
The HD community’s commitment to research is unparalleled. Through ENROLL-HD, tens of thousands of families have shared their personal health data to help build the world’s most robust and comprehensive database of Huntington’s disease. We are profoundly grateful to these families; their participation has provided the scientific foundation that allows researchers to understand HD in “fine-grain” detail. This high-quality natural history data is a gift from the community to the scientific world, intended to make clinical trials smarter, faster, and more effective.
Urgency, Grounded in Scientific Rigor
Huntington’s Disease Society of America (HDSA) stands for urgency with rigor. We believe that speed must never come at the expense of certainty; our families deserve the absolute assurance that a therapy is safe and effective. A thorough trial design is the essential bridge that transforms a hopeful candidate into a proven treatment.
The Role and Impact of Placebos and Sham-Controlled Trials.
The randomized, sham-controlled (placebo) study remains the gold standard for clinical evidence, providing the highest level of scientific certainty. However, HDSA recognizes that for a terminal, progressive disease like Huntington’s, this design carries a heavy weight.
For our families, a two-year sham-controlled period is not a “neutral” observation window; it is a period of active, irreversible neurodegeneration. Every month spent in a placebo/sham arm represents a loss of neurons that no future treatment can restore. By the time a sham-group participant may eventually receive the therapy, they may have progressed past the therapeutic window where a treatment could have best preserved their quality of life.
FDA and the Need for Regulatory Flexibility in Rare Diseases. regulatory flexibility
Congress has directed U.S. Food and Drug Administration (FDA) to apply “regulatory flexibility” for rare diseases—tailoring approaches when traditional trials are not feasible or would unduly delay access. HDSA urges a path forward that upholds FDA’s high standards while recognizing the realities of terminal rare diseases and the practical consequences of trial designs that may be infeasible for participants or sponsors.
Without meaningful regulatory flexibility, the downstream impact is real:
Participation will decline. If families believe enrollment could mean years without access to a potential therapy while their disease progresses, fewer people will volunteer—slowing studies, undermining recruitment, and delaying answers for everyone.
Investment will shrink. If expectations are rigid or unpredictable, biotech sponsors may conclude that HD programs are not viable in the United States and redirect limited research dollars to other diseases.
Therapies may move elsewhere. If development pathways become more feasible outside the U.S., companies may prioritize studies and regulatory submissions in other countries—potentially leaving the U.S.-based HD community waiting longer or unable to access therapies that advance abroad.
HDSA Advocacy Strategy: A Rare-Disease System That Works
HDSA’s advocacy strategy champions a rare-disease development system that advances safe innovation without unnecessary delay. We urge a path forward that balances FDA’s high standards with:
Innovative Trial Designs: Appropriate use of real-world evidence and well-characterized external controls (e.g., ENROLL-HD) when scientifically justified.
Benefit–Risk Realities: Per HDSA’s 2024 HD Symptoms and Treatment Impact Survey, many people living with HD report a willingness to accept meaningful treatment risk in exchange for additional years without disease progression.
Clear, Predictable Guidance: Transparent standards on evidence expectations, endpoints, and how uncertainty can be addressed through confirmatory evidence and/or post-market commitments—so sponsors can plan responsibly and families can make informed decisions about participation.
We appreciate uniQure’s stated intent to continue engaging with the FDA, including the request for a Type B meeting in Q2 2026. HDSA’s focus remains on the Huntington’s disease community: advocating for transparency, consistency, and a rare-disease system that protects rigor while ensuring the U.S. HD community is not left behind in access to safe, effective innovation.
Date: March 5, 2026
The Huntington’s disease (HD) community currently has no approved disease-modifying therapies. While existing treatments may help manage certain symptoms, they do not stop or slow the underlying biological progression of the disease. For families living with this terminal, neurodegenerative condition, the search for a treatment that can alter the course of the illness is an urgent necessity.
The Importance of ENROLL-HD
The HD community’s commitment to research is unparalleled. Through ENROLL-HD, tens of thousands of families have shared their personal health data to help build the world’s most robust and comprehensive database of Huntington’s disease. We are profoundly grateful to these families; their participation has provided the scientific foundation that allows researchers to understand HD in “fine-grain” detail. This high-quality natural history data is a gift from the community to the scientific world, intended to make clinical trials smarter, faster, and more effective.
Urgency, Grounded in Scientific Rigor
Huntington’s Disease Society of America (HDSA) stands for urgency with rigor. We believe that speed must never come at the expense of certainty; our families deserve the absolute assurance that a therapy is safe and effective. A thorough trial design is the essential bridge that transforms a hopeful candidate into a proven treatment.
The Role and Impact of Placebos and Sham-Controlled Trials.
The randomized, sham-controlled (placebo) study remains the gold standard for clinical evidence, providing the highest level of scientific certainty. However, HDSA recognizes that for a terminal, progressive disease like Huntington’s, this design carries a heavy weight.
For our families, a two-year sham-controlled period is not a “neutral” observation window; it is a period of active, irreversible neurodegeneration. Every month spent in a placebo/sham arm represents a loss of neurons that no future treatment can restore. By the time a sham-group participant may eventually receive the therapy, they may have progressed past the therapeutic window where a treatment could have best preserved their quality of life.
FDA and the Need for Regulatory Flexibility in Rare Diseases. regulatory flexibility
Congress has directed U.S. Food and Drug Administration (FDA) to apply “regulatory flexibility” for rare diseases—tailoring approaches when traditional trials are not feasible or would unduly delay access. HDSA urges a path forward that upholds FDA’s high standards while recognizing the realities of terminal rare diseases and the practical consequences of trial designs that may be infeasible for participants or sponsors.
Without meaningful regulatory flexibility, the downstream impact is real:
Participation will decline. If families believe enrollment could mean years without access to a potential therapy while their disease progresses, fewer people will volunteer—slowing studies, undermining recruitment, and delaying answers for everyone.
Investment will shrink. If expectations are rigid or unpredictable, biotech sponsors may conclude that HD programs are not viable in the United States and redirect limited research dollars to other diseases.
Therapies may move elsewhere. If development pathways become more feasible outside the U.S., companies may prioritize studies and regulatory submissions in other countries—potentially leaving the U.S.-based HD community waiting longer or unable to access therapies that advance abroad.
HDSA Advocacy Strategy: A Rare-Disease System That Works
HDSA’s advocacy strategy champions a rare-disease development system that advances safe innovation without unnecessary delay. We urge a path forward that balances FDA’s high standards with:
Innovative Trial Designs: Appropriate use of real-world evidence and well-characterized external controls (e.g., ENROLL-HD) when scientifically justified.
Benefit–Risk Realities: Per HDSA’s 2024 HD Symptoms and Treatment Impact Survey, many people living with HD report a willingness to accept meaningful treatment risk in exchange for additional years without disease progression.
Clear, Predictable Guidance: Transparent standards on evidence expectations, endpoints, and how uncertainty can be addressed through confirmatory evidence and/or post-market commitments—so sponsors can plan responsibly and families can make informed decisions about participation.
We appreciate uniQure’s stated intent to continue engaging with the FDA, including the request for a Type B meeting in Q2 2026. HDSA’s focus remains on the Huntington’s disease community: advocating for transparency, consistency, and a rare-disease system that protects rigor while ensuring the U.S. HD community is not left behind in access to safe, effective innovation.