uniQure N.V. (NASDAQ: QURE) has announced the dosing of the first patient in its GenTLE Phase I/IIa clinical trial evaluating AMT-260 for the treatment of refractory mesial temporal lobe epilepsy (MTLE). This milestone marks uniQure's third clinical trial initiation in the past six months, addressing a significant unmet need for patients with focal onset seizures who do not respond to existing treatments.
AMT-260 is an investigational gene therapy consisting of an AAV9 vector designed to locally deliver two engineered microRNAs (miRNAs). These miRNAs are designed to reduce the expression of GluK2 protein subunits, a subtype of glutamate receptor believed to be overexpressed in the hippocampus of patients with refractory MTLE and implicated in triggering seizure activity. The therapy is administered as a one-time treatment.
Preclinical Evidence
Preclinical animal studies have demonstrated that AMT-260 reduces the number of seizures per day in a dose-dependent manner. Furthermore, AMT-260 reduced the expression of GluK2 mRNA and protein in the hippocampus of epileptic mice and in resected hippocampal slices from patients with refractory MTLE.
GenTLE Phase I/IIa Trial Design
The GenTLE trial is a Phase I/IIa multi-center, open-label study conducted in the U.S. It aims to evaluate the safety, tolerability, and exploratory efficacy of two doses of AMT-260 in individuals with refractory MTLE. The study comprises two dose cohorts of six patients each and is actively recruiting at 10 sites, with two additional sites expected to be activated by the end of 2024. More information can be found at www.clinicaltrials.gov (NCT06063850).
The Need for New MTLE Therapies
Temporal lobe epilepsy is a chronic neurologic disorder and the most common form of focal epilepsy, affecting over 600,000 individuals in the United States. Approximately 80% of temporal lobe epilepsy cases are mesial, involving the medial structures of the brain. A significant proportion of MTLE cases are refractory to anti-seizure medications, highlighting the need for novel therapeutic options.
Management Commentary
"The dosing of the first patient in our Phase I/II trial in temporal lobe epilepsy represents an important milestone for uniQure," stated Walid Abi-Saab, M.D., chief medical officer of uniQure. "Nearly one-third of people experiencing focal onset seizures do not respond to currently available treatments and are left with limited therapeutic options. Our investigational agent, AMT-260, which is a one-time administration, has the potential to be a transformative treatment option for these patients. We continue to actively screen patients for the trial and look forward to providing program updates in the new year."
