In 2012, BioMarin began the first clinical trial on affected patients using their recombinant DNA technology cerliponase alfa which is synthesized using Chinese hamster ovarian (CHO) cell lines. After the success of this clinical trial, the U.S. FDA approved the marketing of cerliponase alfa to patients with CLN2 disease. The approval only applied to patients three years or older as the FDA wants to have more data available on children under the age of three before approving it for younger patients. A ten-year study is being performed to assess the long term effects of continued use of this drug. Cerliponase alfa is developed by BioMarin Pharmaceutical and the drug application was granted both orphan drug designation to provide incentives for rare disease research and the tenth Rare Pediatric Disease Priority Review Voucher. Cerliponase alfa was also approved by European Medicines Agency (EMA) on 30 May 2017. In the United Kingdom NICE evaluated cerliponase alfa for the treatment of CLN2 and deemed it not cost-effective. BioMarin announced that the price per infusion is $27,000, coming to $702,000 per year for treatment, though using Medicaid can decrease the cost.In March 2018, cerliponase alfa was approved in the United States as a treatment for a specific form of Batten disease.
Scores from the Motor domain of the scale range from 3 (grossly normal) to 0 (profoundly impaired).The U.S. Food and Drug Administration (FDA) requires the cerliponase alfa manufacturer to further evaluate the safety of cerliponase alfa in CLN2 patients below the age of two years, including device related adverse events and complications with routine use. In addition, a long-term safety study will assess cerliponase alfa treated CLN2 patients for a minimum of ten years.The application for cerliponase alfa was granted priority review designation, breakthrough therapy designation, orphan drug designation, and a rare pediatric disease priority review voucher. The FDA granted approval of Brineura to BioMarin Pharmaceutical Inc. Structure and biomolecular mechanism
Cerliponase alfa is an approximately 59 kDa molecule that codes for 544 amino acids in its proenzyme form while the activated mature enzyme only codes for 368 amino acids. Five amino acid residues have N-linked glycosylation sites. These five residues have additional mannose-6-phosphate (M6P) targeting sequences which function to target enzymes to the lysosome. When the cerliponase alfa proenzyme reaches target neurons during administration, it binds mannose-6-phosphate receptors on the cell surface to trigger vesicle formation around the receptor-proenzyme complex. The more neutral pH of the cytosol promotes binding of the proenzymes M6P targeting sequences to their receptors.