By Lucy Piper, medwireNews Reporter
medwireNews: Cerliponase alfa treatment slows the progression of neuronal ceroid lipofuscinosis type 2 (CLN2) disease for at least 5 years, shows an open-label extension study in The Lancet Neurology.
“After more than 5 years of follow-up, all patients had reached the age at which disease progression would be expected to be very advanced, and our data provide additional information about the efficacy of treatment through the expected phase of more rapid decline,” note Angela Schulz (University Medical Center Hamburg-Eppendorf, Germany) and colleagues.
The extension study involved 23 of 24 patients with CLN2 enrolled in the primary 48-week study conducted at five hospitals in Germany, Italy, the UK and the USA. They continued to receive intracerebroventricular infusions of cerliponase alfa, a recombinant human tripeptidyl peptidase (TPP1) enzyme replacement therapy, at 300 mg every 2 weeks for 240 weeks.
The participants were aged a mean 4.9 years at enrolment between 2013 and 2014 and 63% were girls. The average combined motor and language domain score on the CLN2 Clinical Rating Scale at baseline was 3.5 points.
In all, 17 patients completed a mean 272.1 weeks of treatment and the results showed that they were a significant 86% less likely than 42 historical controls with untreated CLN2 disease from the DEM-CHILD database to have an unreversed 2-point decline or score of 0 (complete loss of ability to ambulate and communicate).
“Although a decline in motor–language score was still seen in treated patients, the attenuation relative to historical controls was clinically meaningful,” say the researchers.
The median time to an unreversed 2-point decline or a score of 0 on the combined motor and language domains was 272 weeks among treated patients, compared with 49 weeks in historical controls.
Schulz et al estimated that the mean rate of decline, after adjusting for baseline covariates, was 0.64 points per 48 weeks among treated children versus 1.99 points among historical controls, giving a significant mean difference of 1.35 points.
Cerliponase alfa treatment was associated with treatment-related complications, with a total of 237 adverse events in 23 patients, but the investigators point out that “these were manageable and did not result in treatment discontinuation.”
The most common of these events were pyrexia (127 events in 11 children), hypersensitivity (16 events in 10 children), seizure (14 events in nine children), vomiting (15 events in six children) and epilepsy (four events in four children).
There were 12 serious adverse events related to treatment in eight children, including hypersensitivity, infusion-associated reaction and pleocytosis, and nine events in six children resulted in device replacement. However, there were no deaths.
Despite not being required to continue treatment after 240 weeks, the researchers note that “all who completed the treatment period did continue to receive infusions and remained on treatment at the time of the 6-month safety follow-up.”
Discussing the findings in a related comment, Rose-Mary Boustany, from the American University of Beirut Medical Center in Lebanon, points out that “an unaddressed question remains the accessibility of recombinant TPP1 enzyme replacement therapy,” which can be limited due to “regulatory approvals and prohibitive costs.”
She concludes that “[c]arrier screening and prenatal diagnosis in at-risk families, or newborn screening, or both, and early diagnosis provide the best possibility for institution of emerging therapies.”
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Lancet Neurol 2024; 23: 60–70