CLN2 Disease Treatment Reduces Rate of Clinical Decline in Children

On April 24, BioMarin Pharmaceutical Inc announced that the New England Journal of Medicine (NEJM) released updated results from a multi-center, open-label, dose-escalation, and ongoing extension study evaluating the efficacy and safety of cerliponase alfa (Brineura) in children with CLN2 disease in the May 2018 issue.

The data released by NEJM displayed a slower rate of decline in motor and language function than historical controls in patients treated with cerliponase alfa. Per 48 weeks among the 23 treated patients, the unadjusted mean rate of decline in the score on the motor—language scale was 0.27±0.35 points as compared with 2.12±0.98 among the 42 historical controls, creating a difference of 1.85±0.21 points (95% CI, 1.51 to 2.18; P<0.001).

Cerliponase alfa is a recombinant form of human tripeptidyl peptidase 1 (TPP1), which is the enzyme deficient in patients with CLN2 disease. Designed to restore TPP1 enzyme activity and break down the storage materials that cause CLN2 disease, cerliponase alfa is an enzyme replacement therapy. It is injected directly into the cerebrospinal fluid in order to reach the cells of the brain and central nervous system.^1.

CLN2, a form of Batten disease, is a rapidly progressing disease characterized by seizures that occur in those aged between 2 and 4 years old. Language development delay is preceded in most cases. Most children with CLN2 lose the ability to walk and talk by age 6 and die between ages 8 and 12.

The primary endpoint of the study was met (the time to a 2-point decline in motor-language score (range 0-6, 0 representing no function and 3 representing normal function for each of the two domains) assessed as mean change per 48 weeks compared to 42 historical controls). Three hundred and forty-five days (49.3 weeks) was the median time to a 2-point decline in motor-language score for natural history. Nine percent of treated patients had declined by 2 points at 345 days, and therefore, did not reach the median time.

Dr Emily de los Reyes, MD, director of the Batten Disease Center of Excellence at Nationwide Children's Hospital in Columbus, Ohio and a clinical trial investigator involved in the study, commented on the drug’s significance. "CLN2 disease is a devastating and rapidly progressing condition that robs children of their motor function, including language and mobility. With the administration of cerliponase alfa, we see a reduction in that loss, which is of paramount importance to a child and their families where every day of sustained function is critical. We appreciate the opportunity to share our findings with the larger community of healthcare providers, and to contribute to the knowledge that can further advance the standard of care in CLN2 and be useful in developing treatments for other forms of Batten disease."

Additionally, in April 2017, the US Food and Drug Administration (FDA) approved cerliponase alfa in an effort to slow the loss of ambulation in symptomatic pediatric patients 3 years of age and older with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2), also known as tripeptidyl peptidase 1 (TPP1) deficiency. The European Commission approved cerliponase alfa in June 2017. Cerliponase alfa is the first approved treatment for children with CLN2.

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References:

1. New England Journal of Medicine Published Open-label Study Showing Brineura (cerliponase alfa) Reduced the Rate of Clinical Decline of Children with CLN2 Disease, a Form of Batten Disease. prnewswire.com/news-releases/new-england-journal-of-medicine-published-open-label-study-showing-brineura-cerliponase-alfa-reduced-the-rate-of-clinical-decline-of-children-with-cln2-disease-a-form-of-batten-disease-300635669.html. Accessed April 25, 2018.