European Commission Grants Marketing Authorisation for VYNDAQEL®  (tafamidis), the First Treatment in the EU for Transthyretin Amyloid Cardiomyopathy (ATTR-CM)

Tafamidis is the only European Commission (EC) authorised medicine proven to reduce mortality and frequency of cardiovascular-related hospitalisations in adults with wild-type or hereditary ATTR-CM. 

Tafamidis is the first authorised medicine in the EU to treat ATTR-CM

Pfizer Ltd, Walton Oaks, UK – [18 February 2020] – Pfizer Ltd announced today that the European Commission (EC) granted marketing authorisation for 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). Tafamidis is the first authorised treatment in the European Union (EU) for patients with ATTR-CM. Prior to this authorisation, treatment options for patients with ATTR-CM were restricted to symptom management, and, in rare cases, heart (or heart and liver) transplant.^[i][i]

“We now have an authorised medicine to treat people living with ATTR-CM, a rare and fatal disease. This represents a big step forward and reflects Pfizer’s commitment to supporting people living with Rare Disease,” said Owen Marks, Head of Rare Disease, Pfizer UK. “We are working with UK authorities to secure access and make the treatment available.”

ATTR-CM is a rare, under-diagnosed and life-threatening disease characterised by the build-up of abnormal deposits of misfolded protein called amyloid in the heart and is defined by restrictive cardiomyopathy and progressive heart failure.^1,[ii][ii] Once diagnosed, the median life expectancy in patients with ATTR-CM, dependent on sub-type, is approximately 2–3.5 years.^[iii][iii]

Professor Zaheer Yousef, consultant cardiologist at University Hospital Wales and Cardiff University commented: “Patients with cardiac amyloid often have a protracted journey with frequent hospital visits, investigations, and lengthy hospitalisations before a diagnosis is reached. Whilst the emergence of new powerful treatments for this otherwise difficult to treat condition are welcomed, initiatives to facilitate early diagnosis should be supported if patients are to gain the benefits of these treatments.”

The EC authorisation of tafamidis is based on results from the Phase 3 ATTR-ACT study, to date, the first completed international, double-blind, randomised, placebo-controlled clinical trial to investigate a pharmacologic therapy for the treatment of ATTR-CM. The study randomly assigned 441 patients with transthyretin amyloid cardiomyopathy in a 2:1:2 ratio to receive an oral daily dose of 20 mg or 80 mg of tafamidis meglumine or placebo for 30 months.^[iv][iv]

In the primary analysis of the study, tafamidis 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<0.001).⁴

Additionally, individual components of the primary analysis demonstrated a statistically significant relative reduction in the risk of all-cause mortality of 30% at 30 months (Absolute Risk Reduction 13.4%, tafamidis 78 (29.5%) vs. placebo 76 (42.9%); Hazard Ratio 0.70, 95% CI: 0.51–0.96) and relative risk reduction in frequency of cardiovascular-related hospitalisation was 32% at 30 months which was also statistically significant (Absolute Risk Reduction 0.22 per year,tafamidis 138 (0.48) per year vs. placebo 76 (0.70) per year; Relative Risk Ratio 0.68, 95% CI: 0.56–0.81).⁴

Tafamidis 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, tafamidis reduced the decline in performance on the six-minute walk test (p<0.001) and reduced the decline in health status as measured by the Kansas City Cardiomyopathy Questionnaire – Overall Summary score (p<0.001).⁴ 

Tafamidis was generally well tolerated in this study, with an observed safety profile comparable to placebo. The frequency of adverse events in patients treated with tafamidis was generally similar and comparable to placebo.⁴The authorisation 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).⁹The safety of the 61 mg dose was not evaluated in ATTR-ACT.