Cerliponase alfa FDA approved to slow loss of ambulation in children of all ages with CLN2 disease

Cerliponase alfa FDA approved to slow loss of ambulation in children of all ages with CLN2 disease | Image Credit: © Calin - © Calin - stock.adobe.com.

Cerliponase alfa (BRINEURA; BioMarin Pharmaceutical Inc) is now FDA approved for children of all ages with neuronal ceroid lipofuscinosis type 2 (CLN2 disease), or tripeptidyl peptidase 1 (TPP1) deficiency after previously being indicated in symptomatic children aged 3 years and older with late infantile CLN2 disease. Regardless if they are symptomatic or presymptomatic, the expanded indication now includes children of all ages.

The supplemental Biologics License Application (sBLA) is based on data from the phase 2 trial "Study 190-203", an open-label, multicenter trial that evaluated cerliponase alfa treatment over the course of approximately 3 years among children aged 1 to 6 years of age at baseline, of which 8 children were younger than 3 years of age.

Results demonstrated that "that intraventricular (intracerebroventricular, ICV)-administered [cerliponase alfa] slowed the decline in motor function and delayed disease onset in children with CLN2 disease, including those who were under 3 years of age," according to BioMarin. These data, presented at the the 20th Annual We're Organizing Research on Lysosomal Diseases meeting, are the first to demonstrate that early treatment initiation before 3 years of age may result in delaying disease onset.

"[The] approval represents a significant step forward in enabling children to be treated with [cerliponase alfa] 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, in a statement. "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 [cerliponase alfa]'s initial approval to support this expanded use in children of all ages, even before they begin to show symptoms."

In the phase 2 trial, children were assessed for decline in the motor domain of the CLN2 Clinical Rating Scale, the domain that measures ambulation. Normal function was a score of 3 while no function was a score of 0. A sustained 2-point loss or an unreversed score of 0 was the definition of a decline. Of children aged younger than 3 years who were treated with cerliponase alfa, none had a 2-point decline or score of 0 in the motor score domain at week 169 (final assessment).

Of the 8 treated children, 7 were matched to 18 untreated children from a natural history cohort. Of the matched natural history comparators, 11 children (61%) experienced an unreversed 2-point decline or score of 0 by final assessment. Conversely, from baseline to final assessment, all 7 matched cerliponase alfa-treated children under 3 years of age maintained a motor score of 3, representing a "grossly normal gait, signifying a delay in disease onset," stated BioMarin.

"Receiving a CLN2 diagnosis is devastating for families as the disease is life-limiting and can severely impact a child's daily functioning and quality of life from a very young age, with symptoms including seizures, speech and language deficits, impaired movement and vision loss," said Ineka Whiteman, PhD, head of Research and Medical Affairs, Batten Disease Support, Research, & Advocacy (BDSRA) Foundation. "The opportunity to start BRINEURA treatment earlier, even before the onset of symptoms, provides newfound hope for the families impacted by this rapidly progressive disease. Importantly, this expanded indication provides further impetus for early diagnosis of CLN2 disease, as we continue advocating for inclusion of CLN2 disease on the RUSP (Recommended Uniform Screening Panel) for newborn screening."

Reference:

US Food and Drug Administration approves BioMarin's BRINEURA (cerliponase alfa) for children under 3 years with CLN2 disease. BioMarin Pharmaceuticals. Press release. July 24, 2024. Accessed July 25, 2024. https://investors.biomarin.com/news/news-details/2024/U.S.-Food-and-Drug-Administration-Approves-BioMarins-BRINEURA-cerliponase-alfa-for-Children-Under-3-Years-with-CLN2-Disease/default.aspx