Data for BioMarin’s ERT for CLN2 (Batten Disease) is Promising. Very Promising.

October 17, 2016

Thanks to James Radke PhD and Rare Disease Report for this piece. 

The 15th International Conference on Neuronal Ceroid Lipfuscinosis (Batten Disease) being held in Boston, MA the past few days has ended on a high note. Angela Schulz, MD, PhD, of the University Medical Center Hamburg-Eppendorf showed off the latest data from the phase 1/2 open-label dose-escalation study and extension study examining the effects of cerliponase alfa in patients with CLN2 disease, a type of Batten disease.

And the results are very promising.

CLN2 disease is a devastating rare disease in which children are born looking and behaving normally but begin a rapid decline in physical and cognitive abilities at around 2 to 4 years of age. Patients typically present initially with language delay and seizures, followed by movement disorders, motor deterioration, dementia, blindness and early death (typically between 10 to 16 years of age).

In the data presented by Dr Schulz, that rapid decline seems to be attenuated by BioMarin’s  enzyme replacement therapy—Cerliponase alfa—which is a recombinant form of tripeptidyl peptidase 1 enzyme (rhTPP1).

In the initial 48-week study, 24 children were enrolled with a mean age of 4.3 years and a mean CLN2 score of 3.6. Subjects were administered a stable dose of cerliponase alfa (300 mg by ICV infusion every 14 days) for at least 48 weeks.  After 48 weeks, all subjects enrolled into an extension study which remains ongoing.

Of the 24, 23 completed the study. One withdrew from the study due to an extreme fear of needles that could not be overcome.

In the 48-week study, the primary endpoint (change in CLN2 score from baseline) was very encouraging.

Of the 23 patients:

  • 13 patients showed no change in CLN2 score
  • 2 patients showed an improvement of 1 point in the CLN2 score
  • 5 patients showed a decrease of 1 point in the CLN2 score
  • 3 patients showed a decrease of 2 points in the CLN2 score

Extension trial

Dr Shulz showed the most recent efficacy data in which the children have been receiving the drug for 81 weeks and overall, the data is even more impressive than at 48 weeks. After 81 weeks of treatment, the mean CLN2 score has remained stable. In contrast, data from a natural history cohort had a decrease of 3 CLN2 points over that time period.

Testing for anti-drug antibodies revealed that 19 patients in the study had antibodies toward the drug but there was no indication that the presence of antibodies had any effect on treatment efficacy.

One sticky point in an otherwise impressive set of data is the secondary endpoint of cortical grey matter volume measurements.  In the 48-week study, cortical grey matter declined 9.7% in the children receiving cerliponase alfa which is only slightly better than the decline seen in an untreated group it was compared to (14.5% decline; n=6).  Dr Shulz did note however, that the variance in this measurement was quite large.

Adverse events

Most frequent drug-related adverse events were pyrexia (46%), seizures (38%), and hypersensitivity (38%).


Dr Shulz concluded that 65% of patients showed no clinical progression up to 48 weeks when given Cerliponase alfa when looking at the 81 week data, 87% of patients showed no clinical progression.

In a press release last month, BioMarin noted that the FDA granted cerliponase alfa Priority Review Status and Breakthrough Therapy designation and that a PDUFA date has been set for April 27, 2017.

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