FDA names AMT-130 a Huntington’s breakthrough therapy
uniQure gene therapy shown to slow disease progression in adults
The U.S. Food and Drug Administration (FDA) has designated uniQure’s gene therapy candidate AMT-130 a breakthrough therapy for its potential to slow the progression of Huntington’s disease, according to the developer.
This status is intended to speed the development and review of medications for serious or life-threatening illnesses that clinical trials have shown may offer benefits over existing treatments. With the designation, developers are given more frequent communication with the FDA regarding the therapy’s development, and a future approval application may be eligible for expedited review.
“Receiving breakthrough therapy designation underscores both the urgent need for effective treatments for Huntington’s disease and the encouraging interim data demonstrating that AMT-130 has the potential to slow disease progression,” Walid Abi-Saab, MD, uniQure’s chief medical officer, said in a company press release.
The designation was granted based on interim data from two ongoing Phase 1/2 clinical trials — one in the U.S. (NCT04120493) and one in Europe (NCT05243017) — in which AMT-130 was found to slow disease progression over two years in adults with early-stage Huntington’s.
Final data from the trials may be sufficient for uniQure to file a biologics license application for approval of AMT-130, the FDA agreed late last year. More updates on the filing are expected in the coming months, according to the company.
Receiving breakthrough therapy designation is “a powerful recognition of the promise of AMT-130 and the important progress we’ve made,” Saab said.
Clinical trials in US, EU now testing AMT-130 in patients
The FDA had already granted the gene therapy candidate orphan drug and fast track designations. Further, AMT-130 was the first treatment in the U.S. to receive regenerative medicine advanced therapy (RMAT) designation for Huntington’s.
All of these statuses are intended to speed a therapy’s clinical development by offering financial incentives and regulatory guidance.
“We deeply value the FDA’s continued commitment to advancing innovative gene therapies for patients with critical unmet needs, and we look forward to working closely with the agency to bring AMT-130 to the Huntington’s disease patient community as quickly as possible,” Saab said.
Huntington’s is caused by mutations in the gene HTT, which contains the genetic instructions for producing huntingtin, a protein believed to be important for the normal development of nerve cells. The HTT gene is marked by segments of three DNA building blocks — C, A, and G, together known as a CAG repeat — that typically appear 10 to 35 times in a row.
In Huntington’s, the CAG repeat is expanded to 36 or more copies, resulting in a longer-than-normal version of the huntingtin protein that is toxic to nerve cells. This can lead to involuntary movements, known as chorea, and a range of other symptoms, such as behavioral and mental health issues.
The one-time therapy AMT-130 is designed to deliver a microRNA — a small piece of genetic material — that specifically binds to the HTT gene’s blueprints. The goal is to prevent the production of the mutant huntingtin protein and potentially ease the disease’s symptoms.
We deeply value the FDA’s continued commitment to advancing innovative gene therapies for patients with critical unmet needs, and we look forward to working closely with the agency to bring AMT-130 to the Huntington’s disease patient community as quickly as possible.
The microRNA is packaged into a modified and harmless adeno-associated virus that works as a delivery vehicle to cells.
The two clinical trials are both testing AMT-130 at two dosage levels — six trillion vector genomes and 60 trillion vector genomes — in patients ages 25 to 65 with early-stage Huntington’s.
Gene therapy candidate found safe, well tolerated in trials
So far, 45 patients have received AMT-130, according to the company. The single dose is delivered directly into the brain during a surgical procedure. The patients are now being monitored for up to five years.
In the U.S. trial, 26 patients were randomly assigned to receive either AMT-130 or a sham surgical procedure. After one year, patients learned which one they had received, and those who underwent the sham procedure could then choose to receive AMT-130.
One year after administration, the low AMT-130 dose was found to be generally safe and well tolerated, and to reduce levels of mutant huntingtin in the cerebrospinal fluid — the liquid that surrounds the brain and spinal cord — by about half.
Two-year data showed that AMT-130 may help patients maintain motor function compared with what would be expected if the disease had followed its natural course, based on data from an external group of 154 untreated patients who took part in natural history studies.
The high dose of AMT-130 resulted in an 80% slowdown of disease progression compared with the control group, as assessed with the composite Unified Huntington’s Disease Rating Scale (cUHDRS), where lower scores indicate worse disability. On average, AMT-130’s high dose led to a smaller decline (mean of 0.2 vs. 1 point).
In the low-dose group, cUHDRS scores decreased by 0.7 points, which was less than in the control group, yet the difference was not statistically significant.
Both trials are expected to end by 2029.
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