Now Approved for Children of All Ages with CLN2 Batten Disease, Regardless of Whether They Yet Show Symptoms
SAN RAFAEL, CA, USA I July 24, 2024 I BioMarin Pharmaceutical Inc. (Nasdaq: BMRN) today 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.
“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.”
The sBLA is supported by data from Study 190-203, a Phase 2, open-label, multicenter trial evaluating BRINEURA treatment over the span of approximately three years in children aged 1-6 years at baseline, including eight children less than 3 years of age. Results from Study 190-203, which were presented at the 20th Annual We’re Organizing Research on Lysosomal Diseases meeting (WORLDSymposium) in February, showed that intraventricular (intracerebroventricular, 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. BRINEURA’s safety profile has been well-characterized, and safety results in children under 3 years of age were similar to the known safety profile of the medicine. In addition to confirming that treatment initiated after 3 years of age significantly slows the progression of CLN2 disease, these are the first data to demonstrate that early treatment initiation before 3 years of age may result in delaying disease onset.
In Study 190-203, children were assessed for decline in the motor domain of the CLN2 Clinical Rating Scale. This domain measures ambulation, with normal function being a score of three and no function being a score of zero. Decline was defined as having a sustained two-point loss or an unreversed score of zero. 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.
“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, Ph.D., head of Research and Medical Affairs at the 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.”
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. During the later stages of the disease, feeding and tending to everyday needs become very difficult. 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.
The neuronal ceroid lipofuscinoses (NCLs) are a heterogeneous group of lysosomal storage disorders that includes the autosomal recessive neurodegenerative disorder CLN2 disease. CLN2 disease is caused by mutations in the TPP1 gene resulting in deficient activity of the enzyme TPP1. In the absence of TPP1, lysosomal storage materials normally metabolized by this enzyme accumulate in many organs, particularly in the brain and retina. Buildup of these storage materials in the cells of the nervous system contributes to the progressive and relentless neurodegeneration, which manifests as loss of cognitive, motor and visual functions.
About BRINEURA
BRINEURA is an enzyme replacement therapy indicated to slow the loss of the ability to walk or crawl (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.
Please click here to see full Prescribing Information or visit www.brineura.com.
About BioMarin
Founded in 1997, BioMarin is a global biotechnology company dedicated to transforming lives through genetic discovery. The company develops and commercializes targeted therapies that address the root cause of genetic conditions. BioMarin’s unparalleled research and development capabilities have resulted in eight transformational commercial therapies for patients with rare genetic disorders. The company’s distinctive approach to drug discovery has produced a diverse pipeline of commercial, clinical, and pre-clinical candidates that address a significant unmet medical need, have well-understood biology, and provide an opportunity to be first-to-market or offer a substantial benefit over existing treatment options. For additional information, please visit www.biomarin.com.
SOURCE: BioMarin Pharmaceutical
Post Views: 6,545
Now Approved for Children of All Ages with CLN2 Batten Disease, Regardless of Whether They Yet Show Symptoms
SAN RAFAEL, CA, USA I July 24, 2024 I BioMarin Pharmaceutical Inc. (Nasdaq: BMRN) today 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.
“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.”
The sBLA is supported by data from Study 190-203, a Phase 2, open-label, multicenter trial evaluating BRINEURA treatment over the span of approximately three years in children aged 1-6 years at baseline, including eight children less than 3 years of age. Results from Study 190-203, which were presented at the 20th Annual We’re Organizing Research on Lysosomal Diseases meeting (WORLDSymposium) in February, showed that intraventricular (intracerebroventricular, 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. BRINEURA’s safety profile has been well-characterized, and safety results in children under 3 years of age were similar to the known safety profile of the medicine. In addition to confirming that treatment initiated after 3 years of age significantly slows the progression of CLN2 disease, these are the first data to demonstrate that early treatment initiation before 3 years of age may result in delaying disease onset.
In Study 190-203, children were assessed for decline in the motor domain of the CLN2 Clinical Rating Scale. This domain measures ambulation, with normal function being a score of three and no function being a score of zero. Decline was defined as having a sustained two-point loss or an unreversed score of zero. 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.
“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, Ph.D., head of Research and Medical Affairs at the 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.”
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. During the later stages of the disease, feeding and tending to everyday needs become very difficult. 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.
The neuronal ceroid lipofuscinoses (NCLs) are a heterogeneous group of lysosomal storage disorders that includes the autosomal recessive neurodegenerative disorder CLN2 disease. CLN2 disease is caused by mutations in the TPP1 gene resulting in deficient activity of the enzyme TPP1. In the absence of TPP1, lysosomal storage materials normally metabolized by this enzyme accumulate in many organs, particularly in the brain and retina. Buildup of these storage materials in the cells of the nervous system contributes to the progressive and relentless neurodegeneration, which manifests as loss of cognitive, motor and visual functions.
About BRINEURA
BRINEURA is an enzyme replacement therapy indicated to slow the loss of the ability to walk or crawl (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.
Please click here to see full Prescribing Information or visit www.brineura.com.
About BioMarin
Founded in 1997, BioMarin is a global biotechnology company dedicated to transforming lives through genetic discovery. The company develops and commercializes targeted therapies that address the root cause of genetic conditions. BioMarin’s unparalleled research and development capabilities have resulted in eight transformational commercial therapies for patients with rare genetic disorders. The company’s distinctive approach to drug discovery has produced a diverse pipeline of commercial, clinical, and pre-clinical candidates that address a significant unmet medical need, have well-understood biology, and provide an opportunity to be first-to-market or offer a substantial benefit over existing treatment options. For additional information, please visit www.biomarin.com.
SOURCE: BioMarin Pharmaceutical
Post Views: 6,545
