Pfizer Inc. announced that the European Commission (EC) has approved VYNDAQEL (tafamidis), a once-daily 61 mg oral capsule, for the treatment of wild-type or hereditary transthyretin amyloidosis in adult patients with cardiomyopathy (ATTR-CM). VYNDAQEL is the first and only treatment approved in the European Union (EU) for patients with ATTR-CM. Prior to this approval, treatment options for patients with ATTR-CM were restricted to symptom management, and, in rare cases, heart (or heart and liver) transplant.
“Until today, there were no approved medicines to treat patients with ATTR-CM in the EU. Today’s approval represents incredible progress for these patients and reflects our steadfast commitment to delivering breakthrough medicines to rare disease patients,” said Paul Levesque, Global President, Pfizer Rare Disease. “Additionally, with today’s milestone, VYNDAQEL is now the first treatment to have two formulations approved in the EU to treat manifestations of transthyretin amyloidosis: one for cardiomyopathy, and one for stage 1 polyneuropathy.”
ATTR-CM is a rare, underdiagnosed and life-threatening disease characterized by the buildup of abnormal deposits of misfolded protein called amyloid in the heart and is defined by restrictive cardiomyopathy and progressive heart failure. Once diagnosed, the median life expectancy in patients with ATTR-CM, dependent on sub-type, is approximately two to 3.5 years.
“Before today, the European transthyretin amyloidosis community had a dire need for new therapeutic options that can improve outcomes for patients with cardiomyopathy,” said Thibaud Damy, MD, coordinator of the French Referral Centers for Cardiac Amyloidosis and past president of the French Heart Failure and Cardiomyopathy group, French Society of Cardiology. “VYNDAQEL represents a major advance for patients, as it can significantly reduce all-cause mortality and the frequency of cardiovascular-related hospitalizations in patients with wild-type or hereditary ATTR-CM.”
The EC approval of VYNDAQEL is based on results from the Phase 3 ATTR-ACT study, the first and only completed global, double-blind, randomized, placebo-controlled clinical trial to investigate a pharmacologic therapy for the treatment of ATTR-CM. The study compared patients who received an oral daily dose of 20 mg or 80 mg of tafamidis meglumine compared to those who received placebo.
In the primary analysis of the study, VYNDAQEL (tafamidis meglumine) demonstrated a significant reduction in the hierarchical combination of all-cause mortality and frequency of cardiovascular-related hospitalisations compared to placebo over a 30-month period in patients with wild-type or hereditary ATTR-CM (p=0.0006). Additionally, individual components of the primary analysis demonstrated a relative reduction in the risk of all-cause mortality and frequency of cardiovascular-related hospitalization of 30% (p=0.026) and 32% (p<0.0001), respectively, with VYNDAQEL versus placebo.
VYNDAQEL also had significant and consistent treatment effects compared to placebo on functional capacity and health status first observed at six months and continuing through 30 months. Specifically, VYNDAQEL reduced the decline in performance on the six-minute walk test (p<0.0001) and reduced the decline in health status as measured by the Kansas City Cardiomyopathy Questionnaire – Overall Summary score (p<0.0001).
VYNDAQEL was well tolerated in this study, with an observed safety profile comparable to placebo. The frequency of adverse events in patients treated with VYNDAQEL was generally similar and comparable to placebo. The approval is also based on findings from an evaluation of the free acid form of tafamidis 61 mg, which demonstrated that one 61 mg capsule of tafamidis free acid corresponds to an 80 mg tafamidis meglumine dose (4 x 20 mg capsules). The safety of the 61 mg dose was not evaluated in ATTR-ACT. The tafamidis 61 mg capsule was developed for patient convenience to enable a single capsule for daily administration.
In 2011, the tafamidis meglumine 20 mg capsule formulation of VYNDAQEL was approved in the EU for transthyretin amyloidosis in adult patients with stage 1 symptomatic polyneuropathy (ATTR-PN) to delay peripheral neurologic impairment.