You are here

New Sub-group Analyses from the Tafamidis Phase 3 Transthyretin Amyloid Cardiomyopathy (ATTR-ACT) Study Presented at 2018 HFSA Annual Scientific Meeting

—Findings from sensitivity and post-hoc analyses were presented during a Late Breaking Clinical Trials Session at the Heart Failure Society of America 22 nd Annual Scientific Meeting— —Results of new analyses of all-cause mortality favored tafamidis across all sub-groups— —29% and 31% reduction in the risk of death observed in wild-type and hereditary sub-groups, respectively—

Tuesday, September 18, 2018 - 9:00am

NEW YORK--(BUSINESS WIRE)--Pfizer Inc. (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
were presented at the ESC Congress 2018 in Munich, Germany
on August 27, 2018 and simultaneously published
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
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 (NCT02791230) and
additional information about requesting access may be found at
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

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

Pfizer Rare Disease

Rare disease includes some of the most serious of all illnesses and
impacts millions of patients worldwide,4 representing an
opportunity to apply our knowledge and expertise to help make a
significant impact on addressing unmet medical needs. The Pfizer focus
on rare disease builds on more than two decades of experience, a
dedicated research unit focusing on rare disease, and a global portfolio
of multiple medicines within a number of disease areas of focus,
including hematology, neuroscience, and inherited metabolic disorders.1

Pfizer Rare Disease combines pioneering science and deep understanding
of how diseases work with insights from innovative strategic
collaborations with academic researchers, patients, and other companies
to deliver transformative treatments and solutions. We innovate every
day leveraging our global footprint to accelerate the development and
delivery of groundbreaking medicines and the hope of cures.

Click here
to learn more about our Rare Disease portfolio and how we empower
patients, engage communities in our clinical development programs, and
support programs that heighten disease awareness.

Working together for a healthier world


At Pfizer, we apply science and our global resources to bring therapies
to people that extend and significantly improve their lives. We strive
to set the standard for quality, safety and value in the discovery,
development and manufacture of health care products. Our global
portfolio includes medicines and vaccines as well as many of the world's
best-known consumer health care products. Every day, Pfizer colleagues
work across developed and emerging markets to advance wellness,
prevention, treatments and cures that challenge the most feared diseases
of our time. Consistent with our responsibility as one of the world's
premier innovative biopharmaceutical companies, we collaborate with
health care providers, governments and local communities to support and
expand access to reliable, affordable health care around the world. For
more than 150 years, we have worked to make a difference for all who
rely on us. We routinely post information that may be important to
investors on our website at
In addition, to learn more, please visit us on
and follow us on Twitter at @Pfizer
and @Pfizer_News,
and like us on Facebook at

DISCLOSURE NOTICE: The information contained in this release is as of
September 18, 2018. Pfizer assumes no obligation to update
forward-looking statements contained in this release as the result of
new information or future events or developments.

This release contains forward-looking information about a potential
indication for tafamidis for the treatment of transthyretin amyloid
cardiomyopathy (the “Potential Indication”) and Pfizer’s rare disease
portfolio, including their potential benefits, that involves substantial
risks and uncertainties that could cause actual results to differ
materially from those expressed or implied by such statements. Risks and
uncertainties include, among other things,
the uncertainties
inherent in research and development, including the ability to meet
anticipated clinical trial commencement and completion dates and
regulatory submission dates, as well as the possibility of unfavorable
clinical trial results, including unfavorable new clinical data and
additional analyses of existing clinical data; the risk that clinical
trial data are subject to differing interpretations, and, even when we
view data as sufficient to support the safety and/or effectiveness of a
product candidate, regulatory authorities may not share our views and
may require additional data or may deny approval altogether; whether
regulatory authorities will be satisfied with the design of and results
from our clinical studies; whether and when any new or supplemental drug
applications may be filed in any jurisdictions for tafamidis for the
Potential Indication; whether and when regulatory authorities in any
such jurisdictions where applications for tafamidis may be pending
(including the application pending with the FDA for the potential
treatment of transthyretin familial amyloid polyneuropathy, for which
the company received a complete response letter in 2012) or filed may
approve any such applications, which will depend on the assessment by
such regulatory authority of the benefit-risk profile suggested by the
totality of the efficacy and safety information submitted, and, if
approved, whether tafamidis will be commercially successful; decisions
by regulatory authorities regarding labeling and other matters that
could affect the availability or commercial potential of tafamidis,
including for the Potential Indication; and competitive developments.

A further description of risks and uncertainties can be found in
Pfizer’s Annual Report on Form 10-K for the fiscal year ended December
31, 2017 and in its subsequent reports on Form 10-Q, including in the
sections thereof captioned “Risk Factors” and “Forward-Looking
Information and Factors That May Affect Future Results”, as well as in
its subsequent reports on Form 8-K, all of which are filed with the U.S.
Securities and Exchange Commission and available at


1 Data on file. Pfizer Inc. New
York, NY.
2 Rapezzi C, Quarta CC, Riva L, et al.
Transthyretin-related amyloidoses and the heart: a clinical overview.
Nat Rev Cardiol. 2010;7:398-408.
3 Ando Y, Coelho T,
Berk JL, et al. Guideline of transthyretin related hereditary
amyloidosis for clinicians. Orphanet J Rare Dis. 2013;8:31.
Pfizer Inc. Rare disease.
Accessed September 13, 2018.


Pfizer Inc.
Media Relations:
Neha Wadhwa
[email protected]
Chuck Triano
[email protected]