Generic Name
Tafamidis
Brand Names
Vyndaqel, Vyndamax
FDA approval date: May 16, 2019
Form: Capsule
What is Vyndaqel (Tafamidis)?
VYNDAQEL and VYNDAMAX are indicated for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization. VYNDAQEL and VYNDAMAX are transthyretin stabilizers indicated for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization.
Approved To Treat
Top Global Experts
Save this treatment for later
Not sure about your diagnosis?
Related Clinical Trials
An Open-label Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Tafamidis in Patients With Transthyretin-mediated Amyloidosis Post Orthotopic Heart Transplantation
Summary: Transthyretin cardiac amyloidosis (ATTR-CA) is a relentlessly progressive disease that can progress to end stage heart failure, at which point recently approved transthyretin production silencing or structure stabilizing therapies provide no clinical benefit. For well-selected individuals, heart transplantation is an excellent therapeutic option to improve survival. Historically, concomitant liver...
A Single Arm, Multicenter, Open-label,Phase IV Clinical Study to Evaluate the Efficacy and Safety of Tafamidis Meglumine Soft Capsules in the Treatment of Adult Patients withTransthyretin Amyloid Polyneuropathy
Summary: The purpose of this study is to evaluate the efficacy and safety of Tafamidis Meglumine Soft Capsules in the Treatment of Adult Patients with Transthyretin Amyloid Polyneuropathy
A Prospective, Single-arm, Multicenter, Observational Safety Surveillance Study of VyndaMx® (Tafamidis Capsule 61 mg) in Patients With Transthyretin Amyloid Cardiomyopathy (ATTR-CM) in India
Summary: The purpose of this study is to learn about the safety of Tafamidis for the treatment of Transthyretin amyloid cardiomyopathy (ATTR-CM) in India. ATTR-CM is a condition that affects people's hearts. Transthyretin is a protein that is made in the liver. In some people this protein stops working and forms clumps called as amyloid. Transthyretin amyloid builds up in heart and stops the heart from pum...
Related Latest Advances
Brand Information
Vyndaqel (tafamidis meglumine)
1INDICATIONS AND USAGE
VYNDAQEL and VYNDAMAX are indicated for the treatment of the cardiomyopathy of wild-type or hereditary transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular mortality and cardiovascular-related hospitalization.
2DOSAGE FORMS AND STRENGTHS
VYNDAQEL is available as:
- tafamidis meglumine 20 mg: yellow, opaque, oblong capsule, printed with "VYN 20" in red.
VYNDAMAX is available as:
- tafamidis 61 mg: reddish brown, opaque, oblong capsule, printed with "VYN 61" in white.
3CONTRAINDICATIONS
None.
4OVERDOSAGE
There is minimal clinical experience with overdose. During clinical trials, two patients accidentally ingested a single VYNDAQEL dose of 160 mg without adverse events. The highest dose of tafamidis meglumine given to healthy volunteers in a clinical trial was 480 mg as a single dose. There was one reported adverse event of mild hordeolum at this dose.
5DESCRIPTION
VYNDAQEL (tafamidis meglumine) and VYNDAMAX (tafamidis) contain tafamidis as the active moiety, which is a selective stabilizer of transthyretin.
The chemical name of tafamidis meglumine is 2-(3,5-dichlorophenyl)-1,3-benzoxazole-6-carboxylic acid mono (1-deoxy-1-methylamino-D-glucitol). The molecular formula is C
Tafamidis meglumine 20-mg soft gelatin capsule for oral use contains a white to pink colored suspension of tafamidis meglumine 20 mg (equivalent to 12.2 mg of tafamidis free acid), and the following inactive ingredients: ammonium hydroxide 28%, brilliant blue FCF, carmine, gelatin, glycerin, iron oxide (yellow), polyethylene glycol 400, polysorbate 80, polyvinyl acetate phthalate, propylene glycol, sorbitan monooleate, sorbitol, and titanium dioxide.
The chemical name of tafamidis is 2-(3,5-dichlorophenyl)-1,3-benzoxazole-6-carboxylic acid. The molecular formula is C
Tafamidis 61-mg soft gelatin capsule for oral use contains a white to pink colored suspension of tafamidis 61 mg and the following inactive ingredients: ammonium hydroxide 28%, butylated hydroxytoluene, gelatin, glycerin, iron oxide (red), polyethylene glycol 400, polysorbate 20, povidone (K-value 90), polyvinyl acetate phthalate, propylene glycol, sorbitol, and titanium dioxide.
6CLINICAL STUDIES
Efficacy was demonstrated in a multicenter, international, randomized, double-blind, placebo-controlled study in 441 patients with wild-type or hereditary ATTR-CM (NCT01994889).
Patients were randomized in a 1:2:2 ratio to receive VYNDAQEL 20 mg (n=88), VYNDAQEL 80 mg (administered as four 20-mg VYNDAQEL capsules) (n=176), or matching placebo (n=177) once daily for 30 months, in addition to standard of care (e.g., diuretics). Treatment assignment was stratified by the presence or absence of a variant TTR genotype as well as baseline disease severity (NYHA Class). Transplant patients were excluded from this study. Table 1 describes the patient demographics and baseline characteristics.
The primary analysis used a hierarchical combination applying the method of Finkelstein-Schoenfeld (F-S) to all-cause mortality and frequency of cardiovascular-related hospitalizations, which was defined as the number of times a subject was hospitalized (i.e., admitted to a hospital) for cardiovascular-related morbidity. The method compared each patient to every other patient within each stratum in a pair-wise manner that proceeded in a hierarchical fashion using all-cause mortality followed by frequency of cardiovascular-related hospitalizations when patients could not be differentiated based on mortality.
This analysis demonstrated a significant reduction (p=0.0006) in all-cause mortality and frequency of cardiovascular-related hospitalizations in the pooled VYNDAQEL 20-mg and 80-mg groups versus placebo (Table 2).
Analysis of the individual components of the primary analysis (all-cause mortality and cardiovascular-related hospitalization) also demonstrated significant reductions for VYNDAQEL versus placebo.
The hazard ratio from the all-cause mortality Cox-proportional hazard model for pooled VYNDAQEL versus placebo was 0.70 (95% confidence interval [CI] 0.51, 0.96), indicating a 30% relative reduction in the risk of death relative to the placebo group (p=0.026). Approximately 80% of total deaths were cardiovascular-related in both treatment groups. A Kaplan-Meier plot of time to event all-cause mortality is presented in Figure 1.
There were significantly fewer cardiovascular-related hospitalizations with VYNDAQEL compared with placebo with a reduction in risk of 32% corresponding to a Relative Risk Ratio of 0.68 (Table 3).
The treatment effects of VYNDAQEL on functional capacity and health status were assessed by the 6-Minute Walk Test (6MWT) and the Kansas City Cardiomyopathy Questionnaire-Overall Summary (KCCQ-OS) score, respectively. A significant treatment effect favoring VYNDAQEL was first observed at Month 6 and remained consistent 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
Abbreviations: 6MWT=6-Minute Walk Test, KCCQ-OS=Kansas City Cardiomyopathy Questionnaire-Overall Summary.
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 four domains including Total Symptoms (Symptom Frequency and Symptom Burden), Physical Limitation, Quality of Life, and Social Limitation. The Overall Summary score and domain scores range from 0 to 100, with higher scores representing better health status. All four domains favored pooled VYNDAQEL compared to placebo at Month 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 of patients with worse KCCQ-OS scores was lower for the pooled VYNDAQEL-treated group compared to placebo, 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
Abbreviation: KCCQ-OS=Kansas City Cardiomyopathy Questionnaire-Overall Summary.
Results 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 across all subgroups (wild-type, variant and NYHA Class I & II, and III), except for CV-related hospitalization frequency in NYHA Class III (Figure 4). Win ratio is the number of pairs of VYNDAQEL-treated patient "wins" divided by number of pairs of placebo patient "wins." Analyses of 6MWT and KCCQ-OS also favored VYNDAQEL relative to placebo within each subgroup.
Figure 4: Results by Subgroup, Dose, and Components of Primary Analysis
Abbreviations: ATTRm = variant transthyretin amyloid, ATTRwt = wild-type transthyretin amyloid, F-S = Finkelstein Schoenfeld, CI = Confidence 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 Month 30 and KCCQ-OS at Month 30 were statistically significant for both the 80-mg and 20-mg doses of VYNDAQEL vs. placebo, with similar results for both doses.
7HOW SUPPLIED/STORAGE AND HANDLING
VYNDAQEL 20-mg (tafamidis meglumine) soft gelatin capsules are yellow, opaque, oblong, and printed with "VYN 20" in red and supplied in the following package configurations:
VYNDAMAX 61-mg (tafamidis) soft gelatin capsules are reddish brown, opaque, oblong, and printed with "VYN 61" in white and supplied in the following package configurations:
8PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information).
9PRINCIPAL DISPLAY PANEL - 20 mg Capsule Blister Card
NDC 0069-1975-12
Vyndaqel
20 mg per capsule
Pfizer Labs.
PEEL & PUSH
10PRINCIPAL DISPLAY PANEL - 20 mg Capsule Blister Card Carton
Vyndaqel
Attention Pharmacist: Vyndaqel is NOT substitutable on a per mg basis
NOT FOR INDIVIDUAL RESALE
Pfizer
Rx only
11PRINCIPAL DISPLAY PANEL - 20 mg Capsule Blister Card Carton Carton
NDC 0069-1975-40
Vyndaqel
Attention Pharmacist: Vyndaqel is NOT substitutable on a per mg basis with other
Pfizer
Rx only
12PRINCIPAL DISPLAY PANEL - 61 mg Capsule Blister Card
NDC 0069-8730-01
Vyndamax™
61 mg per capsule
Pfizer Labs.
PEEL & PUSH
13PRINCIPAL DISPLAY PANEL - 61 mg Capsule Blister Card Carton
NDC 0069-8730-30
Vyndamax™
Attention Pharmacist: Vyndamax is NOT substitutable on a per mg basis with
Pfizer
Rx only
