Rare Daily Staff

Amicus Therapeutics shared positive interim results from its Batten disease gene therapy program that it had licensed from the Abigail Wexner Research Institute, or AWRI, at Nationwide Children’s Hospital in 2018.

Batten disease refers to a broad class of rare, fatal, inherited disorders of the nervous system also known as neuronal ceroid lipofuscinoses, or NCLs, caused by a defect in a specific CLN gene that triggers a cascade of problems that interferes with a cell’s ability to recycle certain molecules. There are 13 known forms of Batten disease, all of which have similar features and symptoms but vary in severity and age of onset.

Most forms of Batten disease begin during childhood and involve progressive loss of independent adaptive skills such as mobility, feeding, and communication. Patients may also experience vision loss, personality changes, behavioral problems, learning impairment, and seizures.  Patients typically experience progressive loss of motor function and eventually become wheelchair-bound, are then bedridden, and die prematurely.

AWRI is conducting an ongoing phase 1/2 clinical study of a single one-time intrathecal administration of AAV-CLN6 gene therapy for the CLN6 form of Batten disease. With no approved treatments, CLN6 Batten disease is a fatal neurologic disease that rapidly robs children of their ability to walk, speak, think, and see.

“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,” said John Crowley, chairman and CEO of Amicus. “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.”

A total of 12 patients have been treated so far. Interim efficacy 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 and Language Score, an assessment of ambulation and speech, showed that the AAV-CLN6 gene therapy demonstrated a positive impact on motor and language function compared to a natural history dataset of 14 patients, as well as in comparisons within sibling pairs. Seven patients (treated at 19 to 66 months of age) maintained their Hamburg score or had an initial change (ranging from +1 to -1 points) followed by stabilization.

The oldest patient in the study (treated at 79 months of age) had a 2 point decline. This compared to greater declines in the natural history dataset, and greater decline in the sibling pairs of three of the patients.

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.

“This data also provides encouragement for many families within the broader Batten disease community who are following the progress of the Amicus gene therapy programs for CLN3, CLN8, and CLN1 disease” said Tauna Batiste, executive director of the Batten Disease Support and Research Association (BDSRA).

Amicus plans to present additional data throughout the year.

Photo: John Crowley, chairman and CEO of Amicus

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