Three years of treatment with Brineura (cerliponase alfa) was seen to effectively and durably delay the progression of late infantile Batten disease, compared to its natural course, in an ongoing and long-term extension study, BioMarin announced.
These new results — focused on motor and language skills — demonstrate that Brineura, the first approved treatment by the U.S. Food and Drug Administration (FDA) and the European Commission for any form of Batten disease, continues to be a safe and effective therapy for children with its late infantile — or CLN2 — disease subtype.
“Every day, week, month and year of maintaining clinical function, including language and mobility, is critical to children with CLN2 disease and their families,” Angela Schulz, MD, lead study investigator at the Children’s Hospital, University Medical Center Hamburg-Eppendorf, in Germany, said in a press release.
“Following these children has allowed us to better understand the effect of the treatment over time, which contributes to the advancement in the standard of care,” she added.
Brineura 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. It is a man-made version of the human TPP1 enzyme, which is present in very low levels in this patient population.
To reach the cells in the brain and central nervous system, Brineura is administrated directly into cerebrospinal fluid that surrounds the brain and spinal cord, with the help of a catheter surgically implanted into the head.
An open-label Phase 1/2 trial (NCT01907087), conducted at an Ohio site and others in Europe, evaluated the effectiveness and safety of 300 mg of Brineura given every two weeks in children ages 3 to 16 with CLN2 disease. The 23 patients who completed that 48-week study chose to continue treatment in this 240-week extension study (NCT02485899). Measures of treatment safety and changes in motor and language skills over its 4.8 years are its primary goals.
Initial results showed that, compared with 42 patients enrolled in the DEM-CHILD NCL Patient Database — a database used to characterize the natural course of disease severity and progression — treatment with Brineura could prevent motor and language function decline in CLN2 children.
This new data showed the durability of improvements in those skills, with motor and language benefits sustained for more than three years in 19 (83%) of the 23 patients.
After two years of treatment with Brineura, patients’ motor-language scores were on average 3.3 points better than those reported for matched children in the natural history database. After three years, the scores were on average 3.8 points higher.
In contrast, natural history patients on average were 12 times more likely to experience and maintain a two-point decline in motor-language scores after three years compared with Brineura-treated patients.
“CLN2 disease is a destructive and rapidly progressing brain disease in children and the data has consistently shown over time that cerliponase alfa can make a big difference in slowing the progression of the disease,” said Hank Fuchs, MD, president of worldwide research and development at BioMarin.
“It is important to us to contribute to the body of medical knowledge of CLN2 disease with data that is useful to the medical community treating these children,” he added.
The long-term extension study, which concludes in July 2020, is continuing to treat 21 children with 300 mg of Brineura given every two weeks. The two children who left the trial did not do so because of “adverse events,” the release states.