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Brineura (cerliponase alfa), the first and only approved treatment for CLN2 disease, or late infantile Batten disease, is effective in delaying motor and language decline in children with the disease, a review suggests.

The review study, “Review of Cerliponase Alfa: Recombinant Human Enzyme Replacement Therapy for Neuronal Ceroid Lipofuscinosis Type 2 in Young Children, ”Was published in the Journal of Child Neurology.

Late infantile Batten disease, also known as CLN2 disease, is a rare neurodegenerative disease caused by genetic mutations in the TPP1 gene, which provides instructions for making an enzyme called tripeptidyl peptidase 1 (TPP1).

Normally, the disease manifests itself in toddlers, aged 2 to 4 years, and is characterized by speech and movement disorders, convulsions, rapid neurological decline, epilepsy, and vision loss.

Brineura, an enzyme replacement therapy (ERT) developed by BioMarin, is the first – and currently the only – approved treatment for CLN2 disease. It was approved speak United States Food and Drug Administration (FDA) in 2017 for children 3 years of age and older with this form of Batten disease. Brineura works by replacing the enzyme TPP1.

This review focused on summarizing the main results of clinical trials evaluating the safety and efficacy of Brineura for the treatment of children with CLN2 disease.

Documentary research on two online databases – Medline and Base – and additional sources, including the National Institutes of Health Clinical Trials Registry, has led to the identification of several clinical trials testing the safety and efficacy of Brineura in children with late childhood Batten disease.

A recently completed phase 1/2 trial (NCT01907087) established the safety and efficacy of Brineura for the treatment of this form of Batten disease, thus laying the groundwork for its approval in the United States in 2017.

The trial included 24 children, aged 3 to 16, who received Brineura infusions given directly into their brains at a dose of 30, 100 or 300 mg, every two weeks for at least 48 weeks.

Compared to data from a natural history study, test results found that Brineura slows disease progression, particularly motor and language decline, in children with late infantile Batten disease.

The most common unwanted side effects reported during the study included seizures, fever, vomiting, and upper respiratory tract infections. None of the children discontinued treatment due to side effects and no deaths were reported during the trial.

The 23 children eligible for treatment efficacy analysis continued treatment with Brineura in a 240-week open-label extension study (NCT02485899), which is ongoing and is expected to end in January 2021.

In addition to this extension study, a phase 2 trial (NCT02678689) and an extended access study (NCT02963350) of Brineura are in progress.

The phase 2 trial is studying the safety, tolerability and efficacy of Brineura infusions given directly to the brain every two weeks for 144 weeks. Children with late infantile Batten disease, up to the age of 17, are enrolled in the study by invitation. The trial began in February 2016 and is expected to end in April 2022.

The Expanded Access Study is a multi-center, multinational program that aims to provide access to treatment to children 2 years of age and older who have not been able to participate in other clinical trials. The program is no longer recruiting patients.

“Cerliponase alfa is effective in delaying the progression of motor language decline in patients with neuronal ceroid lipofuscinosis type 2,” the researchers wrote.

“The evidence supporting cerliponase alfa is limited by the few clinical trials and the small number of trial participants (…) However, these limitations are inherently common for rare disease therapies. The publication of ongoing trials and concrete evidence will be important, ”they added.

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