Pfizer Inc. September 18, 2018 (NYSE:PFE) announced today that additional sensitivity and post-hoc analyses from the Tafamidis Phase 3 Transthyretin Amyloid Cardiomyopathy (ATTR-ACT) study provide further detail on the effect of tafamidis across wild-type, hereditary, and New York Heart Association (NYHA) class sub-groups of patients with transthyretin amyloid cardiomyopathy (ATTR-CM).1 Tafamidis is the only investigational treatment that has completed a Phase 3 trial evaluating its safety and efficacy for the treatment of ATTR-CM.1 ATTR-CM is a rare, fatal, and underdiagnosed condition associated with progressive heart failure for which there are currently no approved pharmacologic treatments.2
The findings were presented today during the Late Breaking Clinical Trials session at the Heart Failure Society of America 22nd Annual Scientific Meeting in Nashville, TN. The primary results were presented at the ESC Congress 2018 in Munich, Germany on August 27, 2018 and simultaneously published online in the New England Journal of Medicine (NEJM).
The broader primary results showed tafamidis significantly reduced the hierarchical combination of both all-cause mortality and frequency of cardiovascular-related hospitalizations compared to placebo over a 30-month period (P=0.0006) in patients with wild-type and hereditary ATTR-CM.1 A new sensitivity analysis presented today also demonstrated a significant reduction in the combination of all-cause mortality and frequency of all-cause hospitalization compared to placebo over a 30-month period (P=0.0088).1
In addition, tafamidis reduced the risk of all-cause mortality across all sub-groups (wild-type, hereditary and NYHA I, II and III functional class) versus placebo. This included a 29% and 31% reduction in the risk of death observed in wild-type (HR 0.71; 95% CI [0.474, 1.052]) and hereditary (HR 0.69; 95% CI [0.408,1.167]) sub-groups, respectively.1 Across wild-type and hereditary sub-groups, tafamidis consistently reduced the decline in the six minute walk test distance, a measure of functional capacity, and aspects of quality of life measured by the Kansas City Cardiomyopathy Questionnaire – Overall Score, compared with placebo at Month 30. Tafamidis was also well tolerated, with an observed safety profile comparable to placebo.1
“These additional insights further support tafamidis as a potential treatment option for people with wild-type or hereditary ATTR-CM,” said Brenda Cooperstone MD, Senior Vice President and Chief Development Officer, Rare Disease, Pfizer Global Product Development. “We look forward to learning more through further analyses of this study and continue to work with global regulatory authorities to bring this medicine to patients.”
“Following statistically significant results from the primary analysis of the Phase 3 ATTR-ACT trial, we were eager to look deeper into the efficacy of tafamidis in these key ATTR-CM sub-populations,” said Mathew S. Maurer, MD, Medical Director, HCM Center, New York-Presbyterian Hospital/Columbia University Medical Center, and ATTR-ACT study presenter at the HFSA Scientific Annual Meeting 2018. “The results of these additional analyses of the data reinforce the findings presented at the ESC Congress 2018 and published in the New England Journal of Medicine a matter of weeks ago, underscoring the importance of increasing awareness of this potentially deadly condition and diagnosing patients early in the course of their disease journey.”
In light of the seriousness of the disease and the lack of pharmacologic treatment options, Pfizer has established an expanded access treatment protocol to make tafamidis available to ATTR-CM patients who may benefit from treatment prior to regulatory approval. The expanded access treatment protocol is posted on clinicaltrials.gov (NCT02791230) and additional information about requesting access may be found at www.pfizercares.com. Access to these programs may vary by country; physicians may contact their local Pfizer Medical department for further information. Interested ATTR-CM patients should contact their local physician to discuss whether accessing tafamidis may be an appropriate option.
Tafamidis was granted Orphan Drug Designation for ATTR-CM in both the EU and US in 2012 and in Japan in 2018. In June 2017 and May 2018, respectively, the US Food and Drug Administration (FDA) granted tafamidis Fast Track and Breakthrough Therapy designations for ATTR-CM. Additionally, in March 2018, the Ministry of Labor Health and Welfare in Japan granted SAKIGAKE designation to tafamidis for this indication.
About the ATTR-ACT Study
ATTR-ACT is a Phase 3 international, multicenter, double-blind, placebo-controlled, randomized, 3-arm clinical study in 441 patients with ATTR-CM that investigated the efficacy, safety, and tolerability of an oral daily dose of 20 mg or 80 mg tafamidis meglumine capsules compared to placebo. The study included both patients with the hereditary (ATTRm) form of the disease, and those with wild-type (ATTRwt) form, which is not hereditary and may occur as people age. The primary analysis of the study, which compared a pooled tafamidis (80 mg and 20 mg) treatment group to placebo, was the hierarchical combination of all-cause mortality and frequency of cardiovascular-related hospitalizations over a 30-month period in patients with transthyretin amyloid cardiomyopathy.
The ATTR-ACT study demonstrated tafamidis significantly reduced all-cause mortality (29.5% vs. 42.9%; hazard ratio = 0.70, 95% confidence interval [CI] 0.51-0.96, P=0.0259) and cardiovascular-related hospitalizations (0.48 vs 0.70 annualized rate; relative risk ratio = 0.68, 95% CI 0.56-0.81, P1
This represents a 30% reduction in the risk of mortality and 32% reduction in the rate of cardiovascular-related hospitalization. The findings also showed a consistent directional mortality benefit of tafamidis across all sub-groups.1
Secondary study endpoints also showed tafamidis reduced the decline in the six minute walk test distance (P capacity, and reduced the decline in aspects of quality of life measured by the Kansas City Cardiomyopathy Questionnaire – Overall Score (P tolerated, with an observed safety profile comparable to placebo.1
For more information on the ATTR-ACT study, go to www.clinicaltrials.gov.
Tafamidis is an investigational treatment for transthyretin amyloid cardiomyopathy and is not approved for this indication.
ATTR-CM is a rare, progressive, and underdiagnosed disease caused by destabilization of a transport protein called transthyretin, which is composed of 4 identical sub units (a tetramer).3 In ATTR-CM, heart failure occurs when unstable tetramers dissociate, resulting in misfolded proteins that aggregate into amyloid fibrils and deposit predominantly in the heart.2,4
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