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Brineura (cerliponase alfa) is an enzyme replacement therapy with BioMarin which helps slow the gradual loss of walking ability in patients with CLN2 disease, a type of Batten disease.

Brineura is the first treatment approved by the United States 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 products inside cell structures called lysosomes cause CLN2 disease, also known as late infantile Batten disease. These patients have mutations in the TPP1 gene, which leads to a deficiency in the enzyme TPP1. When there is not enough functional TPP1 enzyme, toxic waste builds up inside cells and causes them to die.

Brineura is a recombinant human proenzyme, which means that it is not active when a patient receives it for the first time. Specific brain cells then take up the proenzyme and transport it to the lysosomes. Once inside the lysosome, the proenzyme becomes active, replacing the missing TPP1 enzyme and working to break down the waste.

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, aged 3 to 8 years, and the results of a five-year extension study (NCT02485899).

These clinical trials examined the safety and tolerability of Brineura and assessed the efficacy of treatment as measured with the Hamburg Rating Scale, a CLN2-specific tool, after 48 and 72 weeks of treatment and in comparison to the natural history of the disease (its course without treatment). Hamburg measures 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 for two years. Ninety-five percent of children treated did not experience a decline in their ability to walk or crawl, compared to 50% in the natural history of the disease. Data at 48 weeks also showed that 87% of the children who entered the dose escalation study continued to have motor language scores suggesting significantly slower disease progression.

Researchers are also studying Brineura in an open-label Phase 2 clinical trial (NCT02678689) in patients with CLN2 under 18 years of age. The study enrolled 14 children, who received treatment infusions every two weeks for 144 weeks (approximately 2.7 years). Investigators will monitor them for adverse events, immune reactions, and changes in the Hamburg CLN2 rating scale.

The test results will again be compared to natural history data for CLN2. This study is expected to end in April 2022.

Other details

Brineura is infused directly into the fluid surrounding the patient’s brain, a method known as intraventricular infusion. Before treatment begins, 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 two weeks. The recommended dose of Brineura is 300 mg. Some patients require treatment with antihistamines or corticosteroids before treatment with Brineura.

The most common side effects reported in the Phase 1/2 study included seizures, fever, vomiting, and upper respiratory tract infections.

Last updated: January 14, 2021


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