Accueil / Communiqués / US FDA Accepts Regulatory Submissions for Review of Tafamidis to Treat Transthyretin Amyloid Cardiomyopathy

US FDA Accepts Regulatory Submissions for Review of Tafamidis to Treat Transthyretin Amyloid Cardiomyopathy

Monday, January 14th 2019 at 1:00pm UTC

—FDA grants a Priority Review based on Phase 3 ATTR-ACT study
findings in ATTR-CM—

NEW YORK–(BUSINESS WIRE)– Pfizer Inc. (NYSE: PFE) announced today that the US Food and Drug
Administration (FDA) accepted for filing the company’s New Drug
Applications (NDAs) for tafamidis for the treatment of transthyretin
amyloid cardiomyopathy (ATTR-CM). Pfizer has submitted two NDAs based on
two forms of tafamidis: meglumine salt and free acid. Tafamidis is the
only product to complete a Phase 3 trial evaluating its efficacy,
safety, and tolerability in patients with ATTR-CM, a rare, fatal, and
underdiagnosed condition.1,2

The tafamidis meglumine form (20 mg capsule) has been granted Priority
Review. The FDA grants Priority Review to medicines that may offer
significant advances in treatment or may provide a treatment where no
adequate therapy exists. The target Prescription Drug User Fee Act
(PDUFA) action date for a decision by the FDA is in July 2019.

The tafamidis free acid form (61 mg capsule) will be under Standard
Review. This form is bioequivalent to the 80 mg tafamidis meglumine
dose, which was administered as four 20 mg capsules in the pivotal
trial; it was developed for patient convenience to enable a single
capsule for daily administration. The target PDUFA action date for a
decision by the FDA is in November 2019.

“The diagnosis of ATTR-CM is often delayed, primarily because disease
awareness is low and patients often present with symptoms similar to
more common causes of heart failure. In fact, we believe less than one
percent of patients living with this disease are currently diagnosed,”
said Brenda Cooperstone MD, Senior Vice President and Chief Development
Officer, Rare Disease, Pfizer Global Product Development. “The FDA’s
filing acceptance is an encouraging step toward our goal of further
raising awareness and providing a treatment option for ATTR-CM patients
who are in desperate need of an approved pharmacologic therapy. We look
forward to working with the FDA to bring the first treatment for this
deadly disease to patients.”

The submission is based on findings from the pivotal Phase 3
Transthyretin Amyloid Cardiomyopathy (ATTR-ACT) study, which evaluated
the efficacy, safety, and tolerability of tafamidis meglumine compared
to placebo for the treatment of patients with ATTR-CM. In the primary
analysis of the study, tafamidis met the primary endpoint, demonstrating
a significant reduction in the hierarchical combination of all-cause
mortality and frequency of cardiovascular-related hospitalizations
compared to placebo over a 30-month period in patients with wild-type or
hereditary ATTR-CM (P=0.0006). Tafamidis was well tolerated, with an
observed safety profile comparable to placebo.3 The primary
results
were presented in a Hot Line session at the ESC Congress
2018 in Munich, Germany, and simultaneously published
online
in the New England Journal of Medicine (NEJM) in
August 2018. Results from additional sub-group
analyses
were presented during the Late Breaking Clinical Trials
session at the Heart Failure Society of America 22nd Annual Scientific
Meeting in Nashville, TN, in September 2018. For more information on the
ATTR-ACT trial, go to www.clinicaltrials.gov.

About Tafamidis3

Tafamidis is an oral, investigational product being evaluated as a
potential treatment for ATTR-CM. Tafamidis is a small molecule that
selectively binds at specific sites on the transthyretin tetramer to
prevent destabilization of the transthyretin transport protein and
formation of amyloid that causes ATTR-CM. Tafamidis is not approved for
any use in the United States.

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 FDA granted tafamidis Fast Track and Breakthrough
Therapy designations for ATTR-CM. In November 2018, the FDA granted
Priority Review designation for the NDA for tafamidis meglumine.
Additionally, in March 2018, the Ministry of Labor Health and Welfare in
Japan granted SAKIGAKE designation to tafamidis for this indication.
Following the SAKIGAKE designation, a regulatory marketing application
for tafamidis for ATTR-CM was submitted to the Pharmaceuticals and
Medical Devices Agency (PMDA) in November 2018.

About the ATTR-ACT Study3

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 compared to
placebo. The study included both patients with the hereditary form of
the disease, and those with wild-type 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.

About ATTR-CM

ATTR-CM is a rare and progressive disease caused by destabilization of a
transport protein called transthyretin, which is composed of four
identical subunits (a tetramer). 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.1,2

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.3

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®

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to people that extend and significantly improve their lives. We strive
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DISCLOSURE NOTICE: The information contained in this release is as of
January 14, 2019. 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 other jurisdictions for tafamidis for
the Potential Indication; whether and when the FDA and the PMDA may
approve the pending applications for tafamidis for the Potential
Indication and whether and when regulatory authorities in any such other
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 for the Potential
Indication or any other potential indications for tafamidis 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 
www.sec.gov and www.pfizer.com.

References

1 Maurer MS, Elliott P, Merlini G, et. al. Design and rationale of the
phase 3 ATTR-ACT clinical trial (tafamidis in transthyretin
cardiomyopathy clinical trial). Circ Heart Fail. 2017;10:1-7.
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 Data on file. Pfizer Inc. New York, NY.
4
Pfizer Inc. Rare disease. http://www.pfizer.com/health-and-wellness/health-topics/rare-diseases/areas-of-focus.
Accessed January 11, 2019.

Contacts

Media Relations: Neha Wadhwa
212-733-2835
Neha.Wadhwa@pfizer.com

Investor
Contact: Chuck Triano
212-733-3901
Charles.E.Triano@pfizer.com

Source: Pfizer Inc.


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