Brineura is the first approved treatment by the U.S. Food and Drug Administration and the European Commission for any form of Batten disease. Brineura is also approved in Scotland, England, and Wales.
How does Brineura work?
Similar to other types of Batten disease, genetic mutations that prevent cells from effectively breaking down waste material inside cellular structures called lysosomes cause CLN2 disease, also known as late infantile Batten disease. These patients have mutations in the TPP1 gene, which leads to TPP1 enzyme deficiency. When there is not enough functional TPP1 enzyme, toxic waste accumulates inside cells and causes their death.
Brineura is a recombinant human proenzyme, meaning that it is not active when a patient first receives it. Specific cells in the brain then take up the proenzyme and transport it to lysosomes. Once inside the lysosome, the proenzyme becomes active, replacing the missing TPP1 enzyme and working to break down waste material.
Brineura in clinical trials
Brineura’s approval was based on the results of a Phase 1/2 open-label, dose-escalation trial (NCT01907087) in 24 patients with CLN2 disease, ages 3 to 8, and results from a five-year extension study (NCT02485899).
These clinical trials looked at the safety and tolerability of Brineura and assessed the treatment’s effectiveness as measured with the Hamburg rating scale, a CLN2-specific tool, after 48 and 72 weeks of treatment and in comparison with the disease’s natural history (its course without treatment). Hamburg measures the children’s ability to walk or crawl, ranging from loss of walking or crawling to regular walking or crawling, as well as motor-language scores.
Results, published in the New England Journal of Medicine in 2018, showed that Brineura helped children with CLN2 disease maintain their ability to walk or crawl over two years. Ninety-five percent of treated children did not experience a decline in their ability to walk or crawl, compared with 50% seen in the disease’s natural history. Data at 48 weeks also showed that 87% of children who concluded the dose-escalation study continued to have motor-language scores suggesting substantially slower disease progression.
Researchers are also investigating Brineura in an open-label Phase 2 clinical trial (NCT02678689) in CLN2 patients under age 18. The study recruited 14 children, who are being given treatment infusions every other week for 144 weeks (about 2.7 years). Investigators will monitor them for adverse events, immune reactions, and changes in the Hamburg CLN2 rating scale.
Trial results will again be compared to natural history data for CLN2. This study is expected to conclude in April 2022.
Brineura is infused directly into the fluid surrounding the patient’s brain, a method known as intraventricular infusion. Before the treatment can begin, surgeons place an intraventricular access device in a patient’s skull. After this procedure, patients can receive Brineura treatments, lasting about four-and-a-half hours every other week. The recommended dose of Brineura is 300 mg. Some patients require treatment with antihistamines or corticosteroids before Brineura treatment.
The most common side effects reported in the Phase 1/2 study included convulsions, fever, vomiting, and upper respiratory tract infections.
Last updated: Jan. 14, 2021
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