rial, while one patient died at age 7.8 months dueto disease progression, and one patient withdrew from the study at age 11.9 months. The19 surviving patients who were continuing in the trial ranged in age from 9.4 to 18.5 months. Bythe data cutoff, 13 of the 19 patients continuing in the trial reached 14 months of age withoutpermanent ventilation, one of the study’s co-primary efficacy endpoints. In addition to survival,assessment of the other co-primary efficacy endpoint found that 10 of the 21 patients (47.6%)
achieved the ability to sit without support for ≥ 30 seconds between 9.2 and 16.9 months of age(mean age was 12.1 months). Based on the natural history of the disease, patients who met thestudy entry criteria would not be expected to attain the ability to sit without support, and onlyapproximately 25% of these patients would be expected to survive (i.e., being alive withoutpermanent ventilation) beyond 14 months of age. In addition, 16 of the 19 patients had notrequired daily NIV use.
Comparison of the results of the ongoing clinical trial to available natural history data of patients
with infantile-onset SMA provides primary evidence of the effectiveness of ZOLGENSMA.
The completed clinical trial enrolled 15 patients (6 male and 9 female) with infantile-onset SMA,3 in a low-dose cohort and 12 in a high-dose cohort. At the time of treatment, the mean age ofpatients in the low-dose cohort was 6.3 months (range 5.9 to 7.2 months), and 3.4 months(range 0.9 to 7.9 months) in the high-dose cohort. The dosage received by patients in the low-dose cohort was approximately one-third of the dosage received by patients in the high-dosecohort. However, the precise dosages of ZOLGENSMA received by patients in this completedclinical trial are unclear due to a change in the method of measuring ZOLGENSMAconcentration, and to decreases in the concentration of stored ZOLGENSMA over time. Theretrospectively-estimated dosage range in the high-dose cohort is approximately 1.1 × 1014 to 1.4
× 1014 vg/kg.
By 24 months following ZOLGENSMA infusion, one patient in the low-dose cohort met theendpoint of permanent ventilation; all 12 patients in the high-dose cohort were alive withoutpermanent ventilation. None of the patients in the low-dose cohort were able to sit withoutsupport, or to stand or walk; in the high-dose cohort, 9 of the 12 patients (75.0%) were able to sitwithout support for ≥ 30 seconds, and 2 patients (16.7%) were able to stand and walk withoutassistance. Comparison of the results of the low-dose cohort to the results of the high-dosecohort shows a dose-response relationship that supports the effectiveness of ZOLGENSMA.
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
ZOLGENSMA is shipped frozen (≤ -60C [-76F]) in 10 mL vials with 2 fill volumes (either5.5 mL or 8.3 mL).
ZOLGENSMA is provided as a customized kit to meet dosing requirements for each patient [seeDose and Administration (2.1)], with each kit containing:
• Two (2) to nine (9) vials of ZOLGENSMA (see below)
• One alcohol wipe per vial
Kit sizes and National Drug Codes (NDC) are provided in Table 3.
Table 3: ZOLGENSMA Kit Sizes
ZOLGENSMA Kit Configuration
Patient Weight (kg) 5.5 mL viala
8.3 mL vialb Total Vials per Kit NDC Number
2.6 – 3.0 0 2 2 71894-120-02
3.1 – 3.5 2 1 3 71894-121-03
3.6 – 4.0 1 2 3 71894-122-03
4.1 – 4.5 0 3 3 71894-123-03
4.6 – 5.0 2 2 4 71894-124-04
5.1 &nd |
