tent through Month 30 on both 6MWT distance and KCCQ-OS score (Figure 2 and Table 4).
Figure 2: Change from Baseline to Month 30 in 6MWT Distance and KCCQ-OS Score
Panel A shows change from Baseline to Month 30 in pooled VYNDAQEL patients compared with placebo patients in 6MWT distance.
Panel B shows change from Baseline to Month 30 in pooled VYNDAQEL patients compared with placebo patients in KCCQ-OS score.
The Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) score is composed of fourdomains including Total Symptoms (Symptom Frequency and Symptom Burden), Physical Limitation, Qualityof Life, and Social Limitation. The Overall Summary score and domain scores range from 0 to 100, with higherscores representing better health status.
All four domains favored pooled VYNDAQEL compared to placebo atMonth 30, and demonstrated similar treatment effects to the KCCQ-OS score (Figure 2 and Table 4). The
distribution for change from Baseline to Month 30 for KCCQ-OS (Figure 3) shows that the proportion ofpatients with worse KCCQ-OS scores was lower for the pooled VYNDAQEL-treated group compared toplacebo, and the proportion with improved scores was higher (Figure 3).
Figure 3: Histogram of Change from Baseline to Month 30 in KCCQ-Overall Summary Score
Table 4: 6MWT Distance and KCCQ-OS Scores
Endpoints Baseline Mean (SD) Change from Baseline to
Month 30, LS Mean (SE)
Treatment
Difference from
Placebo
LS Mean (95%
CI)
Pooled
VYNDAQEL
N=264
Placebo
N=177
Pooled
VYNDAQEL
Placebo
6MWT
(meters)
351
(121)
353
(126)
-55
(5)
-131
(10)
76
(58, 94)
KCCQ-OS 67
(21)
66
(22)
-7
(1)
-21
(2)
14
(9, 18)
Abbreviations: 6MWT = 6-Minute Walk Test; KCCQ-OS = Kansas City Cardiomyopathy Questionnaire-Overall Summary; SD = standarddeviation; LS = least squares; SE = standard error; CI = confidence intervalResults from the F-S method represented by win ratio for the combined endpoint and its components (all-cause
mortality and frequency of CV-related hospitalization) consistently favored VYNDAQEL versus placebo acrossall subgroups (wild type, variant and NYHA Class I & II, and III), except for CV-related hospitalizationfrequency in NYHA Class III (Figure 4).
Win ratio is the number of pairs of VYNDAQEL-treated patient“wins” divided by number of pairs of placebVYNDAQEL relative to placebo within each subgroup.
Figure 4: Results by Subgroup, Dose,
Abbreviations: ATTRm = variant transthyretin amyloid, ATTRwt
Interval
*F-S results presented using win ratio (based on all-cause mortality and frequency of cardiovascular hospitalization)Heart transplants and cardiac mechanical assist devices treated as death.
Results of the primary analysis, 6MWT at Monthfor both the 80-mg and 20-mg doses of VYNDAQEL
16. HOW SUPPLIED/STORAGE
VYNDAQEL 20-mg (tafamidis meglumine)“VYN 20” in red and supplied in the following package configurations:
Package ConfigurartionsCarton of 4 intermediary cartons. Eachintermediary carton contains 3 blistercards. Each blister card contains10 capsules. (120 total capsules)
VYNDAMAX 61-mg (tafamidis) soft gelatin capsules are reddish brown, opaque, oblong, and“VYN 61” in white and supplied in the following package configurations:
Package ConfigurationCarton of 3 blister cards. Each blister cardcontains 10 capsules. |
