BioMarin Pharmaceutical Inc. announced positive 48-week results from its Phase 1/2 pivotal study 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.
The average rate of clinical decline for motor and language function in patients receiving cerliponase alfa treatment the primary efficacy endpoint was approximately 80% less than the expected rate of decline in the untreated population, preserving essential function in the majority of treated patients (p <0.0001). Treatment with 300 mg cerliponase alfa administered via intracerebroventricular (ICV) infusion every other week was generally safe and well-tolerated in 24 patients and resulted in disease stabilization in 65% (15 of 23) of patients treated over a 48-week period, based on the Hamburg Motor + Language CLN2 rating. BioMarin estimates the incidence of CLN2 disease is approximately one in 200,000 with approximately 1,200 to 1,600 children in BioMarin's commercial territories.
In the phase 1/2 study, 87% of patients experienced attenuation of their disease compared to the expected rate of decline observed in available natural history data. The primary endpoint of the study is a standardized mobility (motor) and language score using a CLN2 disease-specific rating scale. The scale separately measures performance of mobility and language with normal function in each being a score of 3 and no function being a score of 0. The highest score possible is 6. Natural history of the disease shows an average of 2.1 units of decline over 48 weeks in 41 untreated patients followed longitudinally. The mean decline in 21 evaluable subjects receiving cerliponase alfa treatment was 0.43 units over 48 weeks (p < 0.0001 compared to a 2-point/48 week decline derived from available natural history). Of the 23 evaluable subjects, two were not included in the rate of decline evaluation, as these subjects entered the study with the maximum motor-language score of 6, were not actively declining prior to treatment initiation and remained at 6 during the treatment period.
An interim analysis from an ongoing extension study suggests durability of therapeutic effect. The mean change from baseline in the first nine patients receiving cerliponase alfa treatment was an improvement of +0.2 units over 72 weeks compared to the expected decline observed in a natural history cohort of approximately -3.13 units. Of those nine patients, three gained 1 point, five remained with a stable score and one lost 1 point. In the four patients who received cerliponase alfa for up to 88 weeks, the mean change from baseline was a decline of -0.5 units compared to the expected decline observed in a natural history cohort of approximately -3.83 units.
Additional analysis of cerliponase alfa for the treatment of CLN2 disease will be presented at the International Child Neurology Congress in Amsterdam at the beginning of May.
