You might have heard of Orphan Drug designation – and maybe even Rare Pediatric Disease designation. But have you heard of Regenerative Medicine Advanced Therapy (RMAT) designation? Described in Section 3033 of the 21st Century Cures Act, RMAT designation is granted to cell therapies, human cell or tissue products, or therapeutic tissue engineering products that are intended to treat, cure, modify, or reverse rare, serious, and life-threatening conditions. To qualify for this designation, a therapy must also show the potential – using clinical evidence – to fill unmet needs within that specific disease community. This designation comes with benefits such as Priority Review, increased FDA interaction, and the possibility of using surrogate endpoints, among others.
On June 3, 2024, gene therapy company uniQure shared that its investigational gene therapy AMT-130 received RMAT designation for the indication of Huntington’s disease. AMT-130 is not only the first singular-administration gene therapy product to enter clinical testing for Huntington’s disease, but also the first therapeutic candidate to receive this designation for this disease. The gene therapy works by using a viral vector delivery system to deliver a functional gene encoding a microRNA to bind to and lower huntingtin, a protein that scientists believe plays a role in neuronal health and function. In Huntington’s disease, the HTT gene mutation leads to abnormally long and toxic chains of huntingtin.
The RMAT designation follows Phase 1/2 data on AMT-130 from the clinical setting. Within the United States-based study, researchers evaluated how safe, well-tolerated, and effective AMT-130 was in 26 individuals with early-onset Huntington’s disease. The participants were split into two cohorts: one of which received a low dose of the gene therapy, and the other which received a high dose. Another study from Europe split 13 participants into two cohorts. After comparing the data to available data from a natural history study, the FDA and uniQure found that AMT-130 seemed to confer benefits. Additional data will be available later this year.
Huntington’s Disease: The Facts
In most cases, this rare and progressive neurodegenerative disorder affects adults, with the average age of diagnosis in someone’s 30s or 40s. There is a juvenile form of Huntington’s disease, though this is often more aggressive and has poorer outcomes. An estimated 3-7 out of every 100,000 people has Huntington’s disease. This disease causes neurons in the brain to break down and die, leading to changes in physical and mental capabilities. Huntington’s disease may manifest as:
- Chorea: uncontrolled twitching or jerking that may worsen as the disease progresses
- Cognitive decline: forgetfulness, confusion, difficulty retaining or learning new information, poor decision-making
- Emotional conflict: depression or anxiety, mood swings, impulsivity, changes in behavior or personality, paranoia
- Motor issues: twitching or shrugging, dysphagia (difficulty swallowing), gait abnormalities, problems with balance and coordination, tremors
Unfortunately, there is no cure for Huntington’s disease – and no way to slow its progression or reverse the damage caused. Doctors may prescribe drugs like tetrabenazine for chorea, antiepileptic drugs, or antidepressants for symptom control.
If you or a loved one has this condition, consider joining a support group offered by the Huntington’s Disease Society of America (HDSA).
