Patients in the Brineura Single-Arm Clinical Study with Extension and for Patients in a Natural History Cohort (Based on the Cox Proportional Hazards Model Adjusting for Covariates)
Figure 7
Shading represents 95% confidence intervals.
Follow-up for the natural history cohort begins at 36 months of age or greater and at the first time a Motor plus Language CLN2 score less than 6 was recorded.
The Brineura-treated population is the full population (N=24) minus two patients with baseline Motor plus Language CLN2 score = 6.
Covariates: screening age, screening Motor score, genotype: 0 key mutations (yes/no). “Screening age” was defined in the natural history cohort as the age at the first time a Motor plus Language CLN2 score less than 6 was recorded, and no earlier than 36 months of age. The “screening Motor score” of the natural history cohort was defined as the Motor score at the screening age.
Decline is defined as an unreversed (sustained) 2-category decline or unreversed score of 0 in the Motor domain of the CLN2 Clinical Rating Scale.
Motor Domain Scores: Matched Patients Only
To further assess efficacy, the 22 patients from the Brineura clinical study with a baseline combined Motor plus Language CLN2 score less than 6 were matched to 42 patients in the natural history cohort. Patients were matched based on the following covariates: baseline age at time of screening within 3 months, genotype (0, 1, or 2 key mutations), and baseline Motor domain CLN2 score at time of screening.
Using the Motor domain of the CLN2 Clinical Rating Scale, decline was defined as having an unreversed 2-category decline or an unreversed score of 0. At 96 weeks, the matched analysis based on 17 pairs demonstrated fewer declines in the Motor domain for Brineura-treated patients compared to untreated patients in the natural history cohort (see Table 3).
Table 3: Proportion of Matched Symptomatic Pediatric Patients with CLN2 Disease without Decline* in the Brineura Single-Arm Clinical Study with Extension and in the Natural History Cohort assessed at Weeks 48, 72, and 96
Time Point/Period
Natural History Cohort
(N=17)
Brineura-Treated
(N=17)
Difference
Odds Ratio***
n (%)
n (%)
% (95% CI**)
OR (95% CI)
Follow-up through Week 48
13 (76)
16 (94)
18% (-19, 51)
4 (0.4, 200)
Follow-up through Week 72
11 (65)
16 (94)
29% (-7, 61)
5.9 (0.7, 250)
Follow-up through Week 96
6 (35)
16 (94)
59% (24, 83)
11 (1.6, 500)
*Decline is defined as an unreversed (sustained) 2-category decline or unreversed score of 0 in the Motor domain of the CLN2 Clinical Rating Scale.
** Exact confidence interval for risk difference (Santner and Snell)
***Based on McNemar’s Exact test
Matched on baseline age at time of screening within 3 months, genotype (0, 1, or 2 key mutations), and baseline Motor domain CLN2 score at time of screening.
The Brineura-treated population is based on the full population minus two patients with baseline Motor plus Language CLN2 score = 6.
16 HOW SUPPLIED/STORAGE AND HANDLING
Brineura is supplied as a sterile, clear to slightly opalescent and colorless to pale yellow solution for intraventricular infusion and Intraventricular Electrolytes Injection is supplied as a clear to colorless solution for intraventricular infusion; both are included in package 1 of 2. The Administration Kit for use with Brineura
