Regulatory Decision Summary for Vyndamax

This submission cross-referenced the efficacy, safety and pharmacology sections of the authorized New Drug Submission for Vyndaqel (tafamidis meglumine) (Notice of Compliance issued January 20, 2020, control number 228368). In addition, two comparative bioavailability studies were submitted in support of the bridging of the two formulations.

The first study (B3461054) was considered to be pivotal to demonstrate the comparative bioavailability of the two formulations after single dose administration (fasting and fed conditions) and to demonstrate the effect of food on the 61 milligram (mg) tafamidis capsules. The relative bioavailability of Vyndamax (tafamidis) capsules was compared to that of Vyndaqel (tafamidis meglumine) capsules in a single dose 4-way crossover comparative bioavailability study in 18 healthy adult male subjects.

The second study (B3461056) was considered to be pivotal to support the comparative bioavailability of the two formulations after multiple dose administration under fasting conditions. The relative bioavailability of Vyndamax (tafamidis) capsules was compared to that of Vyndaqel (tafamidis meglumine) capsules in a multiple dose 2-way crossover comparative bioavailability study in 30 healthy adult male subjects. Subjects were dosed for 7 days; receiving 61 mg tafamidis (administered as 1 x 61 mg tafamidis capsules) or 48.8 mg tafamidis (administered as 4 x 20 mg tafamidis meglumine capsules) twice daily on Days 1 and 2, followed by once daily for Days 3 to 7, under fasting conditions. The results from Day 7 sampling demonstrated that there was not a significant difference in the rate and extent of absorption of tafamidis from the two formulations.

Based on the results of these two studies, Vyndamax (tafamidis) 61 mg capsules and Vyndaqel (48.8 mg tafamidis as tafamidis meglumine) 4 x 20 mg capsules are considered to have a comparable bioavailability under their conditions of use. 

In order to mitigate any risk of dosing errors, information was added to the Dosage and Administration Section of the Product Monograph to indicate that prescriptions of tafamidis/tafamidis meglumine should specify the salt form and the prescribed dose.

A Risk Management Plan (RMP) for Vyndamax (tafamidis) was submitted and reviewed by the Marketed Health Products Directorate and is considered acceptable. 

Overall, the benefit-harm-uncertainty assessment of Vyndamax is considered favorable for the treatment of adult patients with cardiomyopathy due to transthyretin-mediated amyloidosis, wild type or hereditary, to reduce cardiovascular mortality and cardiovascular-related hospitalization.