Amicus Gene Therapy Effective After 2 Years in CLN6 Batten Children, Interim Results Show

Amicus Therapeutics‘ investigational gene therapy AT-GTX-501 stabilized motor and language function in children with variant late infantile neuronal ceroid lipofuscinosis 6 disease — also known as CLN6 Batten disease — two years after treatment, according to interim data from a Phase 1/2 clinical trial.  

The ongoing trial (NCT02725580) is evaluating the safety and efficacy of a one-time injection of the therapy into the spinal canal (intrathecal) in CLN6 Batten patients, ages 1 year and older, who are able to walk with assistance.

AT-GTX-501 uses an inactivated adeno-associated virus (AAV) as a vehicle to deliver a functional copy of the CLN6 gene, which is mutated in people with the condition, causing the toxic buildup of deposits called lipofuscins, particularly in cells of the central nervous system (brain and spinal cord). 

“We are pleased to share these positive interim clinical data for our intrathecal AAV gene therapy with the CLN6 community,” Jeff Castelli, PhD, chief development officer of Amicus, said in a press release. “This data continues to suggest that our gene therapy has the potential to be a treatment option for children living with CLN6 Batten disease.”

Results were recently presented as a virtual poster titled, “Single-dose AAV9-CLN6 gene transfer stabilizes motor and language function in variant late infantile neuronal ceroid lipofuscinosis 6 (vLINCL6) disease: interim results from the first clinical gene therapy trial,” at the Joint 16th International Child Neurology Congress and 49th Annual Child Neurology Society Meeting. 

After receiving AT-GTX-501, patients returned for clinical visits on days seven, 14, 21, and 30, and then every three months up to 24 months. 

Disease progression was tracked by changes in Hamburg Motor & Language (HML) Scale scores, a measure of mobility and speech difficulties, with a combined scale from zero to six. Lower scores reflect more severe disability. 

Evaluation of 12 patients at 12 months showed the mean rate of decline was 0.4 points, compared with a drop of 1.2 points in 16 patients from a group derived from a previous CLN6 natural history study (NCT03285425).

After 24 months, data were available for eight patients, who showed a 0.6 mean rate of decline versus 2.4 points from the natural history group. 

Of these eight patients, one (12.5%) demonstrated an HML aggregate score increase greater than one, two patients (25%) had no score change, four (50%) showed a one-point decrease, and one (12.5%) dropped more than two points. 

In contrast, six of the 16 participants from the natural history group had an HML decrease of one point, and the remaining 10 (62.5%) had a decrease of more than two.  

“I remain pleased with the progress of this trial as well as our collection of natural history data to further inform the results for the AAV-CLN6 gene therapy,” said Emily de los Reyes, MD, PhD, principal investigator of the trial and professor of clinical pediatrics and neurology at The Ohio State University College of Medicine. “The interim results show that this investigational gene therapy has the potential to slow the neurological disease progression in children with CLN6 Batten disease.”

Interim safety data were available for 13 patients, which showed that AT-GTX-501 was generally well tolerated. Serious adverse events were reported in five patients, four of which were considered related to treatment, including vomiting, fever, and upper abdominal pain. All four recovered, and there was no other pattern of adverse events related to the AAV vehicle or an anti-CLN6 immune response. 

Participants who complete this study have the option to join a long-term follow-up study (NCT04273243) that opened in January and runs until 2035.

AT-GTX-501 was granted rare pediatric disease and orphan drug designations by the U.S. Food and Drug Administration; in the EU, it has PRIME and orphan medicinal product designations. These designations provide incentives and resources to encourage the development of therapies that focus on diseases with few treatment options.

Amicus expects feedback on AT-GTX-501 from regulatory agencies in 2021.