Schulz A, Ajayi T, Specchio N, de Los Reyes E, Gissen P,
Ballon D, Dyke JP, Cahan H, Slasor P, Jacoby D, Kohlschütter A; CLN2 Study
Group. Study of Intraventricular Cerliponase Alfa for CLN2 Disease. N Engl J
Med. 2018 Apr 24. doi: 10.1056/NEJMoa1712649. [Epub ahead of print]
Abstract
Background Recombinant human tripeptidyl peptidase 1
(cerliponase alfa) is an enzyme-replacement therapy that has been developed to
treat neuronal ceroid lipofuscinosis type 2 (CLN2) disease, a rare lysosomal
disorder that causes progressive dementia in children. Methods In a
multicenter, open-label study, we evaluated the effect of intraventricular
infusion of cerliponase alfa every 2 weeks in children with CLN2 disease who
were between the ages of 3 and 16 years. Treatment was initiated at a dose of
30 mg, 100 mg, or 300 mg; all the patients then received the 300-mg dose for at
least 96 weeks. The primary outcome was the time until a 2-point decline in the
score on the motor and language domains of the CLN2 Clinical Rating Scale
(which ranges from 0 to 6, with 0 representing no function and 3 representing
normal function in each of the two domains), which was compared with the rate
of decline in 42 historical controls. We also compared the rate of decline in
the motor-language score between the two groups, using data from baseline to
the last assessment with a score of more than 0, divided by the length of
follow-up (in units of 48 weeks). Results Twenty-four patients were enrolled,
23 of whom constituted the efficacy population. The median time until a 2-point
decline in the motor-language score was not reached for treated patients and
was 345 days for historical controls. The mean (±SD) unadjusted rate of decline
in the motor-language score per 48-week period was 0.27±0.35 points in treated
patients and 2.12±0.98 points in 42 historical controls (mean difference, 1.85;
P<0.001). Common adverse events included convulsions, pyrexia, vomiting,
hypersensitivity reactions, and failure of the intraventricular device. In 2
patients, infections developed in the intraventricular device that was used to
administer the infusion, which required antibiotic treatment and device
replacement. Conclusions Intraventricular infusion of cerliponase alfa in
patients with CLN2 disease resulted in less decline in motor and language
function than that in historical controls. Serious adverse events included
failure of the intraventricular device and device-related infections. (Funded
by BioMarin Pharmaceutical and others; CLN2 ClinicalTrials.gov numbers,
NCT01907087 and NCT02485899 .).
____________________________________________________________________________
Methods
Initial treatment dose was 30 mg, 100 mg, or 300 mg; then
the 300-mg dose was administered to all patients for at least 96 weeks.
The time until a 2-point decline in the score on the motor
and language domains of the CLN2 Clinical Rating Scale (which ranges from 0 to
6, with 0 representing no function and 3 representing normal function in each
of the two domains) was the primary outcome, and this was compared with the
rate of decline in 42 historical controls.
Rate of decline in the motor–language score was compared
between the two groups using data from baseline to the last assessment with a
score of more than 0, divided by the length of follow-up (in units of 48
weeks).
Results
Researchers enrolled 24 patients, 23 of whom constituted the
efficacy population.
For treated patients, the median time until a 2-point
decline in the motor–language score was not reached, while for historical
controls, it was 345 days.
In treated patients, the mean (±SD) unadjusted rate of
decline in the motor–language score per 48-week period was 0.27±0.35 points,
and in 42 historical controls, was 2.12±0.98 points (mean difference, 1.85;
P<0.001).
Convulsions, pyrexia, vomiting, hypersensitivity reactions,
and failure of the intraventricular device were recognized as common adverse
events.
Infections developed in the intraventricular device that was
used to administer the infusion in 2 patients, which required antibiotic
treatment and device replacement.
https://www.mdlinx.com/neurology/medical-news-article/2018/04/30/cerliponase-alfa-enzyme-replacement-therapy-dementia/7511705
See: http://childnervoussystem.blogspot.com/2018/04/cerliponase-alfa-for-cln2-disease.html (I am 67, after all)
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