Cerliponase Alfa Shows Long-Term Success in CLN2 Disease

June 25, 2019
Matt Hoffman
Matt Hoffman

Matt Hoffman, Senior Editor for NeurologyLive, has covered medical news for MJH Life Sciences, NeurologyLive’s parent company, since 2017. He hosts the NeurologyLive Mind Moments podcast, as well as Second Opinion on Medical World News. Follow him on Twitter @byMattHoffman or email him at mhoffman@neurologylive.com

Patients with CLN2 disease have shown a maintained treatment benefit, high rate of response, and lowering rates of seizure occurrence over 3 years in an ongoing extension trial.

Nicola Specchio, MD, PhD

After 3 or more years of treatment with cerliponase alfa (Brineura, BioMarin), patients with CLN2 disease have experienced a persistent treatment benefit, responder rates, and reduction in rates of seizures in an ongoing multicenter extension study, Study 190-202.

The recombinant human form of tripeptidyl peptidase 1 enzyme (rhTPP1) was the first approved treatment for forms of Batten disease, such as CLN2 disease. Among the 23 patients who continued from the original 48-week Study 190-201, the extension responder rates were at 83% (n=19) with a 12-fold reduction in the risk of a 2-point loss on the motor-language scale at 3 years.

Results of the study, led by Nicola Specchio MD, PhD, department of neuroscience, Bambino Gesu Children's Hospital, were presented in a poster at the 2019 International Epilepsy Congress, June 22-26, in Bangkok, Thailand.

Specchio and co-investigators wrote that additionally, there was an “attenuation in the loss of motor and language function compared with natural history patients” and that “adverse events, including hypersensitivity reactions and [intracerebroventricular] device-related infections, have been managed while maintaining subjects in the study.”

In the trial, the patients were administered cerliponase alfa in a 300-mg dose via an implanted Rickham or Ommaya device into the lateral cerebral ventricle every 14 days. At baseline, the mean motor language CLN2 scores was 3.5 (standard deviation [SD], 1.18; median, 3.0). In total, 71% (n=17) of the patients had ≥1 common mutation—common alleles are c.622C>T and c.509-1G>C—while 29.2% (n=7) had no common mutations.

“A response is defined as the absence of an unreversed 2-point decline or a score of 0 in the motor-language scale at 96 weeks,” Specchio and colleagues wrote, as it denotes a well-defined and significant decline in motor and language function.

At the extension baseline of 48 weeks, the responder rate was 87% (n=20; 95% CI, 66-97; P <.0002), and at 96 weeks, the responder rate remained the same. By 160 weeks, the rate had dipped slightly to the aforementioned 83% (95% CI, 61-95; P <.0013). The “durability of treatment effect is seen in the primary efficacy end point” the investigators noted.

There was also a delay in time to 2-point decline in motor-language scores with cerliponase alfa compared to the natural history of the disease (hazard ratio [HR] 0.08; 95% CI, 0.03-0.21; P ≤.0001). Ultimately, by Day 900, every patient in the natural history cohort had experienced a 2-point decline, whereas there cerliponase alfa group did not reach that point until past Day 1500.

After 96 weeks of therapy, the treatment difference was 3.3 points in motor-language score (0 to 6) change from baseline in favor of those treated with cerliponase alfa. After 160 weeks, the difference was 3.8 points in favor of the treated-group. As for change in motor-language (0 to 12) change from baseline, the respective treatment differences at 96 and 160 weeks were 5.1 and 6.8 points, both in favor of the treatment group.

A medical history of epilepsy or seizures was present in 92% (n=22) and 96% (n=23) experienced ≥1 seizure during the study period. From Week 0 to 24, the percent of patients experiencing a seizure was 88% (n=21), which decreased to 61% (n=14) by Week 72 to 96. By the last recorded date, in Week 168, the proportion of patients with seizures had been reduced to 59% (n=13). The proportion was lowest during Weeks 144 to 168, in which 48% (n=11) of patients experienced a seizure.

With respect to safety, every patient experienced at least 1 adverse event (AE). Notably, Specchio and colleagues wrote that “no deaths and no discontinuations/dose reductions due to AEs” occurred. The most common AEs were seizure (96%), pyrexia and upper respiratory tract infection (83%), and vomiting (75%). Serious AEs occurred in a number of patients, with hypersensitivity (29%) and device-related infections (21%) occurring most often.

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Specchio N, Schulz A, Gissen P, et al. Persistent treatment effect of cerliponase alfa in children with CLN2 disease: A 3 year update from an ongoing multicenter extension study. Presented at: 2019 International Epilepsy Congress. June 22-26, 2019; Bangkok, Thailand. Poster 333.