FDA Approves BioMarin's BRINEURA® for Young Children with CLN2 Disease

BioMarin Pharmaceutical Inc. has announced that the U.S. Food and Drug Administration (FDA) has approved its supplemental Biologics License Application (sBLA) for BRINEURA® (cerliponase alfa). This approval extends the use of BRINEURA to children of all ages with neuronal ceroid lipofuscinosis type 2 (CLN2 disease), also known as tripeptidyl peptidase 1 (TPP1) deficiency. Previously, the medication was only indicated for symptomatic children aged three years and older. The expanded approval means BRINEURA can now be used in children regardless of whether they present symptoms or not.

Hank Fuchs, M.D., president of Worldwide Research and Development at BioMarin, emphasized the importance of this approval, stating that early treatment can significantly alter the natural progression of CLN2 disease. This neurodegenerative condition is marked by rapid onset of symptoms, and each day without treatment can have a profound impact on the affected children and their families. The company has been advocating for this expanded use since BRINEURA's initial approval.

The sBLA approval was based on data from Study 190-203, a Phase 2, open-label, multicenter trial that evaluated BRINEURA's effectiveness over approximately three years in children aged 1-6 years at the study's start, including eight children under three years old. The results, presented at the 20th Annual WORLDSymposium in February, demonstrated that intraventricular (ICV)-administered BRINEURA slowed motor function decline and delayed disease onset in young children, including those under three years. The safety profile of BRINEURA in children under three was consistent with known safety data. The study also provided the first evidence that initiating treatment before three years of age could delay disease onset.

In the trial, children were assessed using the motor domain of the CLN2 Clinical Rating Scale, which measures ambulation. Normal function scores a three, while no function scores a zero. A two-point decline or an unreversed score of zero indicated deterioration. None of the children under three treated with BRINEURA experienced this level of decline by the final assessment (week 169). In contrast, 11 of 18 untreated children in a matched natural history cohort exhibited such a decline. All treated children maintained a motor score of three, indicating a delay in disease onset.

Ineka Whiteman, Ph.D., head of Research and Medical Affairs at the Batten Disease Support, Research, & Advocacy (BDSRA) Foundation, highlighted the devastating impact of CLN2 disease on families. Symptoms often include seizures, speech and language deficits, impaired movement, and vision loss. The ability to start BRINEURA treatment earlier offers new hope for families, emphasizing the importance of early diagnosis and inclusion of CLN2 disease in newborn screening programs.

CLN2 disease is a form of Batten disease caused by mutations in the TPP1 gene, leading to deficient enzyme activity and accumulation of storage materials in many organs, particularly the brain and retina. This buildup results in progressive neurodegeneration, manifesting as loss of cognitive, motor, and visual functions. BioMarin estimates the incidence of CLN2 disease to be about one in 200,000, with many children undiagnosed.

BRINEURA is an enzyme replacement therapy designed to slow the loss of ambulation in children with CLN2 disease. It is a recombinant form of human TPP1 intended to restore enzyme activity and break down the storage materials causing the disease. The treatment is delivered directly into the cerebrospinal fluid surrounding the brain using BioMarin's patented technology. Initially approved in 2017, BRINEURA is the first and only approved treatment for children with CLN2 disease.

BioMarin, founded in 1997, is a global biotechnology company focused on developing therapies for genetic conditions. Its research has led to eight commercial therapies for rare genetic disorders, and it continues to work on a diverse pipeline of candidates that address significant unmet medical needs.