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Real-World Data and Real-World Evidence
Published in Wei Zhang, Fangrong Yan, Feng Chen, Shein-Chung Chow, Advanced Statistics in Regulatory Critical Clinical Initiatives, 2022
Cerliponase alfa (Brineura), an enzyme-replacement therapy, was approved in 2017 by FDA as the first treatment for neuronal ceroid lipofuscinosis type 2 (CLN2) disease. CLN2 disease, also known as late infantile neuronal ceroid lipofuscinosis (NCL) is a rare, autosomal recessive, pediatric neurodegenerative disease caused by gene mutation and is featured by difficulty in coordinating movements (ataxia). Patients often progressed to use of a wheelchair by late childhood. There were no other approved pharmacological treatments for CLN2 other than drugs for symptom management.
External Control Using RWE and Historical Data in Clinical Development
Published in Harry Yang, Binbing Yu, Real-World Evidence in Drug Development and Evaluation, 2021
Qing Li, Guang Chen, Jianchang Lin, Andy Chi, Simon Davies
Batten disease, which is also called neuronal ceroid lipofuscinoses (NCLs), is a family of rare, fatal, inherited disorders of the nervous system. It is estimated that 2–4 births per 100,000 in the United States are affected by Batten disease, which is considered as a rare disease. Batten disease was named after British pediatrician Frederick Batten, who first described the disease in 1903; however, there were no approved drugs until recently. In April 2017, the FDA approved Brineura® (cerliponase alfa), which was developed by BioMarin Pharmaceutical, Inc. as a treatment for a specific form of Batten disease (FDA 2017c). It is the first FDA-approved treatment to slow the loss of walking ability (ambulation) in symptomatic pediatric patients 3 years of age and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl peptidase-1 (TPP1) deficiency. The BLA of Brineura® received priority review and breakthrough therapy designation.
Extrapolation Process in Pediatric Drug Development and Corresponding Bayesian Implementation for Validating Clinical Efficacy
Published in Mani Lakshminarayanan, Fanni Natanegara, Bayesian Applications in Pharmaceutical Development, 2019
Margaret Gamalo-Siebers, Simin Baygani
For example, adult and pediatric trial data were used to establish similar exposure-response relationships for eight anti-epileptic agents with complex partial seizures, thereby supporting full extrapolation of efficacy in future submissions [53]. Remicade® (infliximab) used adult and pediatric trial data to establish similar exposure-response relationships for infliximab (Remicaid) and the adult placebo response as external control to the pediatric trial to support partial extrapolation of efficacy and pediatric labeling in ulcerative colitis [54,55]. Pediatric patients from a real-world registry were used as a historical control comparison in the approval of Brineura® (cerliponase alfa) for a specific form of Batten disease [56].
Advances in the treatment of neuronal ceroid lipofuscinosis
Published in Expert Opinion on Orphan Drugs, 2019
Jonathan B. Rosenberg, Alvin Chen, Stephen M. Kaminsky, Ronald G. Crystal, Dolan Sondhi
When considering different therapeutic approaches, ERT may conceptually be the simplest, but the blood-brain barrier is a major hurdle to the therapeutic enzyme accessing the CNS, the most important target in all NCLs. The recent approval for intraventricular administration of Cerliponase Alfa for the treatment of CLN2 disease is a significant step forward in the field and opens up the possibility of expanding ERT not just to other NCLs but also to other LSDs with neurological involvement [220]. While the approval is a huge breakthrough, it must be remembered that ERT requires lifelong repeated administrations, a significant confounding factor for reasons of cost and access to therapy. Although the cost of the treatment (£500,000/yr) was originally cited by the UK’s National Institute for Health and Care Excellence (NICE) as one reason for it not to recommend Brineura use for National Health System (NHS) [274], after a long delay the product and in the absence of lower cost alternatives, it has now received approval [275].
Managing CLN2 disease: a treatable neurodegenerative condition among other treatable early childhood epilepsies
Published in Expert Review of Neurotherapeutics, 2021
Maria Mazurkiewicz-Bełdzińska, Mireia del Toro, Göknur Haliloğlu, Hidde H. Huidekoper, Ružica Kravljanac, Chris Mühlhausen, Brian Nauheimer Andersen, Igor Prpić, Pasquale Striano, Stéphane Auvin
In 2017, the first ERT for an NCL was approved in the USA and European Union [8,9]. Cerliponase alfa (recombinant human TPP1) is approved for the treatment of CLN2 disease (and specifically for slowing the loss of ambulation in symptomatic children aged ≥3 years in the USA) following trials showing that intracerebroventricular infusions every other week reduce the rate of decline of motor and language function [37]. Trials of cerliponase alfa are ongoing in younger, potentially asymptomatic patients (<3 years old), and for extended periods to understand the long‑term impact of this ERT [38].
Cerliponase alfa for CLN2 disease, a promising therapy
Published in Expert Opinion on Orphan Drugs, 2020
Shawn C. Aylward, Jonathan Pindrik, Nicolas J. Abreu, W. Bruce Cherny, Matthew O’Neal, Emily de Los Reyes
Historically, CLN2 disease has been considered a terminal illness without effective disease-modifying treatments. The advent of cerebral intraventricular ERT has changed the prognosis for children and young adults suffering from this disorder. Food and Drug Administration (FDA) approval for cerliponase alfa has emphasized the importance of early diagnosis, which through early use of precision therapies, may lead to better outcomes. However, the expense of this novel treatment for a rare disease requires more long-term analysis.