Battling Batten disease

Amicus gene therapy brings in positive interim results

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CRANBURY, N.J.—Amicus Therapeutics achieved positive interim results from its CLN6 Batten disease gene therapy program licensed from the Abigail Wexner Research Institute (AWRI) at Nationwide Children’s Hospital.
AWRI is conducting the ongoing Phase 1/2 clinical study of a single one-time intrathecal administration of AAV-CLN6 gene therapy for CLN6 Batten disease. Intrathecal administration is done by injection into the spinal canal, or into the subarachnoid space so that it reaches the cerebrospinal fluid (CSF).
As John F. Crowley, chairman and CEO of Amicus Therapeutics, explained in a conference call, “CLN6 Batten disease is a fatal neurologic disease that rapidly robs children of their ability to walk, speak, think and see, and often ends in death during childhood. There are currently no approved treatments.”
He added that a mutation in the CLN6 gene leads to lysosomal dysfunction at 2 to 3 years of age after typical childhood development. There is an urgent need for treatment, and early intervention is critical. The estimated population for this rare disease is about 1,000 globally.
Dr. Brian Kaspar, former professor of pediatrics, faculty at AWRI; Dr. Kathrin Meyer, principal investigator at AWRI; and their team at AWRI, in collaboration with Dr. Jill Weimer’s laboratory at Sanford Research, developed the AAV gene replacement strategy that is the basis for the AAV-CLN6 gene therapy. Positive interim clinical data are available for the first eight children with CLN6 Batten disease for up to 24 months post-administration of the AAV-CLN6 gene therapy.
The Hamburg Motor & Language Score, an assessment of ambulation and speech, revealed that the AAV-CLN6 gene therapy had a positive impact on motor and language function compared to a natural history dataset, as well as in comparisons within sibling pairs. Treatment with AAV-CLN6 gene therapy was generally well tolerated. This intrathecal AAV-CLN6 gene therapy uses the same capsid as the recently FDA-approved systemic gene therapy, also initially developed at AWRI, for the fatal neurologic disease Spinal Muscular Atrophy Type 1.
Per the Hamburg score, efficacy data demonstrate a positive impact on motor and language function for seven of eight patients treated. These eight patients are from 16 to 25 months post-administration of the gene therapy. Seven patients (treated at 19 to 66 months of age) maintained their Hamburg score or had a small initial change, followed by stabilization. The oldest patient in the study (treated at 79 months of age) had a 2-point decline.
Three treated patients demonstrated stabilization relative to their untreated siblings in the natural history data set who experienced substantial declines in motor and language ability or died over the same time period. For the two pairs of in-study siblings, the younger siblings showed an increase or stabilization in their score compared to their older siblings who had an initial change followed by stabilization. An initial natural history cohort from Nationwide Children’s shows disease progression in all untreated patients, with at least a 2- to 3-point decline in Hamburg Motor & Language score from the initial point of decline over 24 months.
Most adverse events (AEs) were mild and unrelated to treatment in 12 patients in the clinical study (exposure duration 6 to 39 months). No pattern of AEs related to anti-AAV capsid or anti-CLN6 immunogenicity were observed.
According to Crowley, “This program and these initial results represent the heart and soul of who we are and why we do what we do at Amicus. These interim clinical data suggest that our gene therapy in CLN6 Batten disease has the potential to halt the progression of this devastating fatal disease that, untreated, destroys brain function and kills children.”
He added, “It is remarkable that most children in this study appear to show stabilization, particularly the younger children who were able to maintain high baseline motor and language scores for up to two years. We know that brain damage here is irreversible, and early intervention will be critical to preserve the ability to speak and walk. We move forward with a great sense of urgency here for these children and their families.”
“It is gratifying to translate gene therapy from preclinical animal studies to humans, leading to the current data which demonstrate evidence for safety and initial efficacy in the first children treated. I believe this AAV-CLN6 gene therapy has the potential to make a very meaningful impact for children with CLN6 Batten disease and provides great promise to address many types of Batten disease and other neurologic disorders,” Kaspar concluded.

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