ng (touch-pressure and heat-pain), and peripheral nerve electrophysiology. The maximum possible score was 346.32 points, with higher scores representing a greater severity of disease.
The clinical meaningfulness of effects on the mNIS+7 was assessed by the change from baseline to Week 66 in Norfolk Quality of Life-Diabetic Neuropathy (QoL-DN) total score. The Norfolk QoL-DN scale is a patient-reported assessment that eva luates the subjective experience of neuropathy in the following domains: physical functioning/large fiber neuropathy, activities of daily living, symptoms, small fiber neuropathy, and autonomic neuropathy. The version of the Norfolk QoL-DN that was used in the trial had a maximum possible total score of 136 points, with higher scores representing greater impairment.
The changes from baseline to Week 66 on both the mNIS+7 and the Norfolk QoL-DN significantly favored TEGSEDI (TABLE 3, FIGURES 1 and 3). The distributions of changes in mNIS+7 and Norfolk QoL-DN scores from baseline to Week 66 by percent of patients are shown in Figure 2 and Figure 4, respectively.
Table 3: Clinical Efficacy Results from Study 1
CI, confidence interval; LS, least squares; mNIS, modified Neuropathy Impairment Score; QoL-DN,Quality of Life – Diabetic Neuropathy
a All endpoints analyzed using the mixed-effect model repeated measures (MMRM) method.
b A lower value indicates less impairment/fewer symptoms.
cThe primary analysis population for the mNIS+7 analysis included N=95 TEGSEDI patients and N=56 placebo patients
dThe primary analysis population for the Norfolk QOL-DN analysis included N=94 TEGSEDI patients and N=57 placebo patients
Endpoint Baseline Change from Baseline to
Week 66 (LS Mean) TEGSEDI – placebo Treatment Difference LS Mean (95% CI) p-
value
TEGSEDI Placebo TEGSEDI Placebo
Primarya
mNIS+7b, c 80.2 75.3 5.8 25.5 -19.7
[-26.4, -13.0] <0.001
Norfolk QOL-
DNb, d 48.7 48.7 1.0 12.7 -11.7
[-18.3, -5.1] <0.001
Figure 1: Change from Baseline in mNIS+7
Figure 1: Change from Baseline in mNIS+7
Figure 2: Histogram of mNIS+7 Change from Baseline at Week 66
Figure 2: Histogram of mNIS+7 Change from Baseline at Week 66
Figure 3: Change from Baseline in Norfolk QoL-DN Score
Figure 3: Change from Baseline in Norfolk QoL-DN Score
Figure 4: Histogram of Norfolk QoL-DN Change from Baseline at Week 66
Figure 4: Histogram of Norfolk QoL-DN Change from Baseline at Week 66
Patients receiving TEGSEDI experienced similar improvements relative to placebo in mNIS+7 and Norfolk QoL-DN score across all subgroups including age, sex, race, region, NIS score, Val30Met mutation status, and disease stage.
16 HOW SUPPLIED/STORAGE AND HANDLING
TEGSEDI is a clear, colorless to pale yellow solution supplied in a single-dose, prefilled syringe with a SSD. Each prefilled syringe of TEGSEDI is filled to deliver 1.5 mL of solution containing 284 mg of inotersen (equivalent to 300 mg inotersen sodium salt).
TEGSEDI is available in cartons containing 1 or 4 prefilled syringes.
Pack of 1 prefilled syringe: NDC 72126-007-03
Pack of 4 prefilled syringes: NDC 72126-007-01
The Individual Tray contains NDC 72126-007-02
Pharmacy
Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original container and protect from direct light. Do not freeze.
For Patients/Care |
