Brineura Shows Promise Delaying Disease Progression in Children with CLN2, Review Suggests

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 Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2,” was published in the Journal of Child Neurology.

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

Normally the disease manifests in toddlers, ages 2–4, and is characterized by speech and movement impairments, seizures, 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 by the U.S. Food and Drug Administration (FDA) in 2017 for children 3 and older with this form of Batten disease. Brineura works by replacing the TPP1 enzyme.

This review focused on summarizing the main findings of clinical trials assessing the safety and effectiveness of Brineura for the treatment of children with CLN2 disease.

A literature search on two online databases — Medline and Embase — and additional sources, including the National Institutes of Health Clinical Trials Registry, led to the identification of several clinical trials testing the safety and effectiveness of Brineura in children with late infantile Batten disease.

A recently completed Phase 1/2 trial (NCT01907087) established the safety and effectiveness of Brineura for the treatment of this form of Batten disease, setting the foundation for its approval in the U.S. in 2017.

The trial enrolled 24 children, ages 3–16, who received infusions of Brineura administered directly into their brain 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, trial findings revealed that Brineura slowed disease progression, particularly motor and language decline, in children with late infantile Batten disease.

The most common adverse side effects reported during the study included convulsions, 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.

All 23 children who were 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 conclude in January 2021.

In addition to that extension study, a Phase 2 trial (NCT02678689) and an expanded access study (NCT02963350) of Brineura are ongoing.

The Phase 2 trial is investigating the safety, tolerability, and effectiveness of Brineura infusions administered directly to the brain, every two weeks for 144 weeks. Children with late infantile Batten disease, up to age 17, are being enrolled in the study by invitation. The trial started in February 2016 and is expected to conclude in April 2022.

The expanded access study is a multi-center, multi-national program that seeks to provide treatment access to children 2 and older who were unable 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 for patients with neuronal ceroid lipofuscinosis type 2,” the researchers wrote.

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