Editors' (re)View: FDA’s rare disease push; Strides in Batten disease treatment
FDA’s rare disease push
Last week, the FDA announced its plan to establish a Rare Disease Innovation Hub (aka the ‘Hub’) with the goal of expediting development and approval of treatments for rare disease.
The agency outlined three primary functions of the Hub:
- Serve as a single point of connection and engagement with the rare disease community, including patient and caregiver groups, trade organizations and scientific/academic organizations
- Enhance intercenter collaboration within the FDA to address common scientific, clinical and policy issues related to rare disease product development
- Advance regulatory science with dedicated workstreams for consideration of novel endpoints, biomarker development and assays, innovative trial design, real world evidence and statistical methods
The Hub will be co-led by CDER director, Dr. Patrizia Cavazzoni and CBER director, Dr. Peter Marks (a personal fav of mine). In addition, the agency is hiring for a newly-created senior leadership position: Director of strategic coalitions for the Hub (apply here).
The move is part of a continued push by the agency to advance treatments for the estimated 10,000+ rare diseases affecting more than 30 million people in the U.S.
Last September, the FDA launched its Support for Clinical Trials Advancing Rare Disease Therapeutics (START) pilot program (which quickly picked up the nickname ‘operation warp speed for rare diseases’). Several companies, including Moderna and Neurogene, recently announced that their rare disease programs had been chosen for the pilot.
The agency’s push is well timed, with its Rare Pediatric Disease Priority Review Voucher program set to expire on September 30 if it isn’t granted reauthorization by Congress — a move that advocates warn would be a blow to rare disease drug development.
The HUB and START program are much-needed efforts in an area of tremendous unmet need and are worth celebrating. —Karen Langhauser
Strides in Batten disease treatment
This week, the FDA approved BioMarin's supplemental BLA for Brineura (cerliponase alfa), now extending its use to children of all ages with neuronal ceroid lipofuscinosis type 2 (CLN2) disease, also referred to as Batten disease.
Previously, Brineura was only indicated for symptomatic children aged three and older. The new approval includes both symptomatic and presymptomatic children, offering an earlier treatment alternative. First approved in 2017, the drug received Priority Review, Breakthrough Therapy, and Orphan Drug designations, along with a Rare Pediatric Disease Priority Review Voucher
CLN2 disease, also known as tripeptidyl peptidase 1 (TPP1) deficiency, causes seizures and rapid neurodegeneration, leading to loss of motor and cognitive functions and often death by early adolescence.
The decision was based on data from Study 190-203, which evaluated Brineura over three years in children aged one to six, including those under three years old. Results demonstrated that Brineura slowed the decline in motor function and delayed disease onset in younger children.
Brineura — the first and only treatment for CLN2 disease — is an enzyme replacement therapy that restores TPP1 activity in the brain and central nervous system, administered intraventricularly to deliver the enzyme directly to the brain.
The drug comes with a hefty price tag. According to Bloomberg, Brineura cost $27,000 per biweekly infusion, or about $702,000 a year, making it one of the world's most expensive drugs at the time it was approved. BioMarin noted that most patients were on Medicaid, reducing the cost to $486,000 after discounts.
Other treatment options for CLN2 disease are limited. Symptomatic treatments such as antiepileptic drugs can help manage seizures, but they do not address the underlying disease progression.
Currently, several gene therapy candidates are being developed for CLN2 disease. Regenxbio’s RGX-181 delivers the TPP1 gene to the CNS for long-term correction, while RGX-381 targets retinal issues to prevent vision loss. Lexeo Therapeutics' LX1004, in phase 1/2 trials, also aims to deliver a functional TPP1 gene to the central nervous system.
Between Brineura’s expanded approval and advancements in CLN2 research, there is renewed hope for significantly improving the quality of life and prognosis for children affected by this disease. — Andrea Corona
