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Applications of RWE for Regulatory Uses
Published in Kelly H. Zou, Lobna A. Salem, Amrit Ray, Real-World Evidence in a Patient-Centric Digital Era, 2023
Eleanor E. Panico, Corinne S. Pillai, Ewa Filipowska, Kelly H. Zou
Aside from label expansion, there have been, on occasion, utilization of RWE to support full approval of a new therapy. This is evidenced by the US FDA approval of BRINEURA® for a rare pediatric neurologic disease leading to early death (Real-world Evidence – From Safety to a Potential Tool for Advancing Innovative Ways to Develop New Medical Therapies, FDA approves first treatment for a form of Batten disease, US FDA). The efficacy of BRINEURA® was established in a non-randomized, single-arm dose escalation clinical study in 22 symptomatic pediatric patients with CLN2 (neuronal ceroid lipofuscinosis type 2) disease and compared to 42 untreated patients with CLN2 disease from a natural history disease registry (an independent historical control group) (Real-world Evidence – From Safety to a Potential Tool for Advancing Innovative Ways to Develop New Medical Therapies, FDA approves first treatment for a form of Batten disease, US FDA). This scenario demonsrates that registries can provide a beneficial and potentially high-quality source of RWD and can capture clinical outcomes of a defined patient population.Depending on the nature of the disease and feasibility of carrying out additional clinical research, RWE can reduce or, in some cases, eliminate the need for sponsors to conduct additional lengthy, expensive trials before they can make a medicine available to patients in need.
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.
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
Studies have shown that ERT products have varying degrees of success in treating lysosomal storage disorders, and are dependent on initiating therapy at an early stage of disease development as well as achieving widespread distribution. Early intervention is key to halting or slowing disease progression prior to irreversible pathology. Since several of the NCL defects arise in proteins that are secreted (CLN1, CLN2, CLN5, CLN10, CLN13), ERT could potentially provide functional versions of the relevant protein to the site of need in the CNS. Importantly, only low amounts of the enzyme (~5–10% of the endogenous levels) are typically needed for therapeutic effects [7,163,164]. There may be the development of humoral immunity against repeat administered proteins that could limit efficacy, induce inflammatory responses, and reduce cost effectiveness. Finally, the manufacturing of the protein product requires extensive methods development and processes that include qualified host cell lines and validated purification schemes. Despite these challenges, one of the first successes in NCL therapeutic development is Brineura®, an FDA-approved intracerebroventricular administration of ERT for CLN2 [166].