18-month data on juvenile Batten therapy shows positive efficacy
Theranexus’ investigational therapy Batten-1 stabilized motor symptoms
Treatment with the investigational therapy Batten-1 (miglustat) for 18 months, or about 1.5 years, stabilized motor symptoms in patients with juvenile Batten disease, according to the final results from a Phase 1/2 trial.
The progression of motor symptoms was considerably slowed down, as evaluated using the modified Unified Batten Disease Rating Scale (UBDRS) physical assessment score. Compared with the beginning of the trial, or its baseline, the mean score increased by 1.83 in Batten-1 treated patients, but increased by 6.04 in untreated patients evaluated in a natural history study.
“The data collected after 18 months of treatment with Batten-1 further reinforce its highly promising potential. We currently no longer observe a marked progression of motor symptoms in the [six] patients treated,” Gary Clark, MD, chief of Child Neurology at Texas Children’s Hospital and the trial’s principal investigator, said in a press release from the Beyond Batten Disease Foundation (BBDF).
Juvenile Batten disease, the most common form of Batten, is caused by mutations in the CLN3 gene and results in the fatty molecule lipofuscin accumulating inside lysosomes, the small cellular structures responsible for clearing waste products. This accumulation occurs in many cell types, but nerve cells are particularly sensitive, leading to progressive neurological decline in motor and cognitive functions, along with loss of vision.
Batten-1 partially lowers the toxic accumulation of waste molecules, reducing the inflammation and neuronal death that contributes to the progressive loss of function in people with the disorder.
Results of treatment with Batten-1
The Phase 1/2 trial (NCT05174039), which was sponsored by BBDF, assessed Batten-1’s safety, tolerability, pharmacological properties, and efficacy in six patients, ages 17 or older, who received an oral capsule up to a maximum daily dose of 600 mg for up to 18 months.
Preliminary results after about two months showed it was generally safe and well tolerated. The most common side effects included light to moderate gastrointestinal problems. The therapy’s pharmacokinetics, that is, its movement into, through, and out of the body, were consistent with expectations.
Batten-1 also reduced blood levels of neurofilament light chain (NfL), a biomarker of nerve cell degeneration, by an average of 17% after six months and by 32% after a year. The treatment was also able to lower globotriaosylceramide (Gb3), another fatty molecule that accumulates in juvenile Batten disease, after a year, by 45%.
The trial is also evaluating the effect on visual acuity, brain volumes by MRI, and thickness of the neuronal layer of the retina by optical tomography scans.
The patients will be able to continue to receive treatment through a compassionate use program following their participation in the trial.
“These results highlight the strong therapeutic potential Batten-1 on the clinical course of the disease,” said Theranexus’ CEO Mathieu Charvériat, PhD.  “In this context, we are exploring different funding options to ensure we have the adequate resources to launch a phase 3 pivotal trial.”
Both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have approved the design of the upcoming Phase 3 study based on safety data from the Phase 1/2 trial. Theranexus has launched a global offering to fund the trial, which will use a liquid formulation of the therapy, which is better suited for pediatric patients.
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