Brineura (cerliponase alfa) is an enzyme replacement therapy developed by BioMarin that helps slow the progressive loss of walking ability in patients with a type of Batten disease known as CLN2 disease.

Brineura is the first approved treatment by the U.S. Food and Drug Administration (FDA) and the European Commission (EC) for any form of Batten disease.

How Brineura works

Similar to other types of Batten disease, CLN2 disease is caused by genetic mutations that prevent cells from effectively breaking down waste material inside cellular structures called lysosomes. CLN2 disease patients have mutations in the TPP1 gene, leading to TPP1 enzyme deficiency. When there is not enough functional TPP1 enzyme, toxic waste accumulates inside cells and cause their death.

Brineura is a recombinant human proenzyme, meaning that it is not active when first infused into a patient. This proenzyme is taken up by specific cells in the brain and then transported to lysosomes. Once inside the lysosome, the proenzyme becomes active, replacing the missing TPP1 enzyme and functioning 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) conducted in 24 patients with CLN2 disease, ages 3 to 8, and results from an ongoing extension study (NCT02485899).

These clinical trials looked at the safety and tolerability of Brineura administered in patients’ brains and assessed the therapy’s effectiveness as measured by a CLN2 disease-specific rating scale score, in comparison with natural history data, after 48 and 72 weeks of treatment. This scale measured 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.

The study found that Brineura helped children with CLN2 disease maintain their ability to walk or crawl over two years. Ninety-five percent of children enrolled in the trial did not experience a decline in their ability to walk or crawl, compared to 50 percent of untreated children. 

Data at 48 weeks also showed that 87 percent of children who concluded the dose-escalation study  continued to have motor-language scores, suggesting substantially slower disease progression compared to 42 patients in the natural history group.

Results of the trials were published in the New England Journal of Medicine.

The extension study will gather data until December 2021 and also will reveal how the treatment affects specific developmental milestones and children’s quality of life.

Other details

Brineura is infused directly into the fluid surrounding the patient’s brain, a method known as intraventricular infusion. Before the treatment can begin an intraventricular access device must be surgically placed into the patient’s skull. After this procedure, Brineura treatments lasting about four-and-a-half hours is performed 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 of Brineura are fever, heart rhythm irregularities, decreased or increased protein in brain fluid, vomiting, seizures, hypersensitivity to heat, cold or other stimulation, hematoma, or an abnormal collection of blood outside the blood vessels, headaches, irritability, increased white blood cell count in brain fluid, and low blood pressure.

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