BioMarin Pharmaceutical Inc. announced that the U.S. Food and Drug Administration (FDA) has approved the company's supplemental Biologics License Application (sBLA) for Brineura (cerliponase alfa) to slow the loss of ambulation in children of all ages with neuronal ceroid lipofuscinosis type 2 (CLN2 disease), also known as tripeptidyl peptidase 1 (TPP1) deficiency. Previously, Brineura was indicated in symptomatic children 3 years of age and older with late infantile CLN2 disease. This expanded indication now includes children of all ages with CLN2 disease, regardless of whether they are symptomatic or presymptomatic.
Clinical Trial Data
The sBLA is supported by data from Study 190-203, a Phase 2, open-label, multicenter trial evaluating Brineura treatment over approximately three years in children aged 1-6 years at baseline, including eight children less than 3 years of age. The study demonstrated that intraventricular (ICV)-administered Brineura slowed the decline in motor function and delayed disease onset in children with CLN2 disease, including those who were under 3 years of age. In the children below 3 years of age treated with Brineura in the trial, none (0%) had a two-point decline or score of zero in the motor score by the final assessment (week 169). Among the eight treated children, seven were matched to 18 untreated children from a natural history cohort. Among the matched natural history comparators, 11 children (61%) experienced an unreversed two-point decline or score of zero by the final assessment. From baseline to final assessment, all seven matched Brineura-treated children below 3 years of age maintained a motor score of three, which represents a grossly normal gait, signifying a delay in disease onset.
Impact on CLN2 Disease Treatment
"Today's approval represents a significant step forward in enabling children to be treated with Brineura as early as possible, when we can have the greatest impact in altering the natural course of disease," said Hank Fuchs, M.D., president of Worldwide Research and Development at BioMarin. "We know that every day counts for families affected by serious genetic conditions such as CLN2 disease, which is characterized by a rapid onset of neurodegenerative symptoms. We have been working diligently since Brineura's initial approval to support this expanded use in children of all ages, even before they begin to show symptoms."
About CLN2 Disease
Children with neuronal ceroid lipofuscinosis type 2 (CLN2 disease), also known as tripeptidyl peptidase 1 (TPP1) deficiency, typically begin experiencing seizures between the ages of 2 and 4 years old, preceded in the majority of cases by language development delay. The disease progresses rapidly with most affected children losing the ability to walk and talk by approximately 6 years of age. Initial symptoms are followed by movement disorders, motor deterioration, dementia, blindness, and death usually occurring between the ages of 8 and 12 years of age. BioMarin estimates the incidence of CLN2 disease is approximately one in 200,000, with up to 1,200 to 1,600 children in the regions of the world where BioMarin operates, many of whom are undiagnosed.
About Brineura
Brineura (cerliponase alfa) is an enzyme replacement therapy indicated to slow the loss of ambulation in pediatric patients with neuronal ceroid lipofuscinosis type 2 (CLN2 disease), also known as tripeptidyl peptidase 1 (TPP1) deficiency, a form of Batten disease. Brineura is a recombinant form of human TPP1, the enzyme deficient in children with CLN2 disease, designed to restore TPP1 enzyme activity and break down the storage materials that cause CLN2 disease. To reach the cells of the brain and central nervous system, the treatment is delivered directly into the fluid surrounding the brain (cerebrospinal fluid) using BioMarin's patented technology. Brineura, the first and only approved treatment for children with CLN2 disease, was initially approved in 2017 by the U.S. Food and Drug Administration and European Commission.
Safety Information
Severe and life-threatening allergic reactions, including anaphylaxis, can occur during Brineura infusions and up to 24 hours after infusion. Intraventricular access device-related infections, including meningitis, were observed with Brineura treatment. Low blood pressure and/or slow heart rate may occur during and following the infusion of Brineura. Infusion-associated reactions (IARs) such as vomiting, seizure, rash, fever (pyrexia), hypersensitivity, and anaphylactic reaction have been observed in patients treated with Brineura.
