uniQure’s plan for AMT-130 approval hits snag at FDA
Agency says it no longer considers data sufficient to support application
The U.S. Food and Drug Administration (FDA) no longer considers available clinical data sufficient to move forward with an application seeking approval of uniQure’s AMT-130 for Huntington’s disease, the company said.
The company had planned to submit a biologics license application (BLA) early next year, based on data from two Phase 1/2 clinical trials — one underway in the U.S. (NCT04120493) and the other in Europe (NCT05243017) — testing the therapy in adults with early-stage Huntington’s. Results showed that AMT-130-treated patients had a 75% slower disease progression than an external group of matched, untreated patients in an observational study.
The timing of a BLA submission “is now unclear,” uniQure said.
“We are surprised by the FDA’s feedback at the recent pre-BLA meeting, which is a drastic change from the guidance the FDA provided in November 2024 that data from the ongoing Phase I/II studies, compared to a natural history external control, may serve as the primary basis for a BLA submission under the Accelerated Approval pathway,” Matt Kapusta, uniQure’s CEO, said in a company press release. “This news is unexpected, and we are truly disappointed for people living with [Huntington’s], who have no disease-modifying treatment options for this devastating disease.”
Accelerated, or conditional, approval allows experimental therapies to be marketed based on early clinical trial results suggesting clinical benefit. Full approval is dependent on additional trial data confirming such benefits.
Company wants to work with FDA on ‘path forward’
“We strongly believe that AMT-130 has the potential to bring substantial benefit to patients, and we remain fully committed to working with the FDA to determine the best path forward to rapidly bring AMT-130 to patients and their families in the U.S,” Kapusta said.
Huntington’s is caused by mutations in the HTT gene, which carries the instructions for producing huntingtin, a protein believed to be important for nerve cell development and function. HTT contains segments of three DNA building blocks — called CAG repeats— typically copied 10 to 35 times in a row.
In Huntington’s, however, the CAG repeats expand to 36 or more copies, producing a longer-than-normal version of the huntingtin protein that becomes toxic to nerve cells. As a result, patients may experience involuntary movements, known as chorea, as well as behavioral and psychiatric symptoms of Huntington’s.
AMT-130 is a one-time gene therapy designed to deliver a microRNA — a small piece of genetic material — that binds to the HTT gene’s blueprints, preventing the production of both healthy and mutated huntingtin proteins.
The microRNA is packaged into a harmless, modified adeno-associated virus that serves as a delivery vehicle to nerve cells. By lowering levels of mutant huntingtin, the therapy is expected to slow or prevent disease progression in Huntington’s.
The two Phase 1/2 clinical trials are testing AMT-130 at either of two doses — six trillion or 60 trillion vector genomes — in adults, ages 25 to 65, with early-stage Huntington’s. The single dose is delivered directly into the brain through a surgical procedure, and patients are being monitored for up to five years.
Consistent with the trial’s two-year data, top-line, three-year readouts from 24 participants suggested that AMT-130 may help slow disease progression compared with what would be expected if the disease had followed its natural course, based on data from an external group of untreated patients in natural history studies.
At three years, scores on the composite Unified Huntington’s Disease Rating Scale (cUHDRS) — a standard measure of how fast the disease is progressing — worsened significantly less, by 75%, in patients treated with high-dose AMT-130 compared with the external group.
The FDA previously recognized the therapeutic potential of AMT-130 by granting it orphan drug, fast track, regenerative medicine advanced therapy, and breakthrough therapy designations. These statuses are intended to speed clinical development and review for therapies that may offer significant benefits over existing options.
Alongside its work with the FDA to find a path toward accelerated approval, uniQure plans to continue discussions with regulators in other regions, including the European Union and the U.K., to advance AMT-130 as a potential gene therapy for Huntington’s worldwide.
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