Amicus’ gene therapy trial offers hope for Batten disease patientsPublished: August 5, 2019
Amicus Therapeutics provides early update on its Phase 1/2 gene therapy trial developed to treat patients with CLN6 Batten disease, an inherited childhood neurodegenerative disorder.
Batten disease (also known as Neuronal Ceroid Lipofuscinoses, NCL) is a group of severe, inherited childhood neurodegenerative disorders caused by mutations in either soluble enzymes or membrane-associated structural proteins that result in lysosome dysfunction.
Over 400 mutations in 13 different genes have been described that cause the various forms of Batten disease and they are the most common cause of inherited neurodegeneration in children. The current trial targets Batten disease caused by mutation in the CLN6 gene.
The hallmarks of the disease include accumulation of lysosomal residual bodies in neurons and extracerebral tissue and loss of neurons. These diseases share common pathological characteristics including motor problems, vision loss, seizures, and cognitive decline, culminating in premature death. Currently, no form of the disease can be treated or cured, with only palliative care to minimise discomfort.
Amicus’ gene therapy program is licensed from the Abigail Wexner Research Institute (AWRI) at Nationwide Children’s Hospital. Interim efficacy data obtained from the first eight children with CLN6 Batten disease treated with one-time AAV-CLN6 gene therapy showed meaningful impact on motor and language function. The treated children were evaluated for up to 24 months post-administration of the gene therapy. The Hamburg Motor & Language Score, an assessment of ambulation and speech, was used to evaluate the changes in motor activity and language in patients over the course of recovery. Data showed that the gene therapy rendered a positive impact on motor and language function and the disease was stabilized over the course of 2 year.
Treatment with AAV-CLN6 gene therapy was generally well tolerated. The study lacked control groups; therefore, Amicus compared the results with the performance of the siblings of patients treated in the trial. For example, one of the patients scored five out of six on the Hamburg Motor & Language scale at the time of treatment and was still at that level 24 months later. In contrast, the score of the sibling of that patient reduced from five to two over the same 24-month window. The Hamburg Motor & Language Score (0-6) separately measures performance of mobility (0-3) and speech (0-3). For each domain, a 3 represents the child’s normal function and a 0 represents no ability to walk or speak, with each point decline representing significant impairment.
Amicus is hopeful with the results and intends to dose additional patients and advance talks with regulators. In parallel, Amicus will continue development of its other gene therapies, that target CLN3, CLN8 and CLN1 Batten disease.
Amicus’ Chairman and CEO John F. Crowley commented: “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. 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 look forward to presenting additional data throughout this year and continuing to advance our CLN6 and other Batten disease gene therapy programs that all apply the same AAV technology platform developed by Dr. Brian Kaspar and his former colleagues at Nationwide Children’s. Early intervention is crucial, so we move forward with a great sense of urgency here for these children and their families.”
Source: Amicus shares early look at Batten disease gene therapy; Website