BioMarin provides update for Brineura (cerliponase alfa) to treat children with CLN2 disease ( a form of Batten disease)

BioMarin Pharmaceutical Inc. announced a program update for cerliponase alfa, a recombinant human tripeptidyl peptidase 1 (rhTPP1) to treat children with CLN2 disease, a form of Batten disease. CLN2 disease is a rapidly progressing, fatal neurodegenerative disease with no approved treatments, where the majority of affected children lose their ability to walk and talk by approximately six years of age.

After 81 weeks, patients treated with cerliponase alfa continue to have motor-language (ML) scores representing substantial attenuation of disease progression compared to natural history. These data are consistent with the data at 48 weeks submitted with the original Biologics License Application (BLA), and demonstrate durable and consistent treatment response. During their initial review of the BLA, the FDA requested an updated efficacy data cut from the ongoing extension study, which the company provided. The FDA designated this submission as a major amendment to the application, thus extending the PDUFA action date by three months to April 27, 2017. The FDA has not communicated their rationale for declaring this submission a major amendment. This review division has extended PDUFA timelines for breakthrough products in the past.

The Agency has advised that they plan to hold an advisory committee meeting at a date to be confirmed per their usual practice of notification in the Federal Register.

The additional data continue to show that the Hamburg Motor + Language CLN2 scores of a majority of treated patients are stable. Natural history of the disease shows an average of 2.1 points of decline over 48 weeks and an expected 3 points of decline over 81 weeks. Updated analysis of the estimated rate of decline including approximately 8 months of additional data continues to show substantial attenuation of disease progression with cerliponase alfa treatment. The mean (95% Confidence Interval) rate of decline of the Motor Language score in points per 48 weeks for the Intent to Treat (ITT) population (n = 23) as of 03 June 2016 was 0.32 (0.13, 0.52) (p < 0.0001 compared to a 2-point decline derived from available natural history), which was based on 81 weeks of treatment. This rate is improved from the corresponding rate of decline reported in the original BLA of 0.48 (0.16, 0.81), which was based on 48 weeks of treatment.The primary analysis, agreed to with FDA, is a responder analysis where patients with decline in CLN2 score remained 87%, as reported in the original BLA. Consistent with previous data cuts, cerliponase alfa administered via intracerebroventricular infusion every 14 days was well tolerated, and no patients discontinued treatment due to adverse events (AEs). Most AEs were Grade 1 or 2, and the majority are consistent with severe, chronic neurologic disease in pediatric patients. The most common events associated with treatment included: pyrexia, hypersensitivity, seizure, epilepsy, vomiting and headache. No new safety signals were observed.