– If approved by the European Commission (EC), VYNDAQEL® will be the first pharmacologic therapy in the EU for patients with transthyretin amyloid cardiomyopathy—

NEW YORK, NY, USA I December 13, 2019 I Pfizer Inc. (NYSE: PFE) announced today that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion recommending the approval of 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).

“The CHMP positive opinion of VYNDAQEL for ATTR-CM reflects our steadfast commitment to improving outcomes for patients living with this rare and fatal disease,” said Brenda Cooperstone, MD, Senior Vice President and Chief Development Officer, Rare Disease, Pfizer Global Product Development. “In ATTR-ACT, VYNDAQEL reduced mortality and the frequency of cardiovascular-related hospitalizations in patients with wild-type or hereditary forms of the disease. If approved, VYNDAQEL would represent a real breakthrough for patients.”

ATTR-CM is a rare, 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.1,2,3 On average, patients live only 2 to 3.5 years following diagnosis.4

“For those living with ATTR-CM, a progressive and fatal rare disease, there are currently no available pharmacologic treatments for patients,” said Jean-Christophe Fidalgo, President of the Amyloidosis Alliance. “The Amyloidosis Alliance applauds the CHMP opinion, and we hope the EC will swiftly approve VYNDAQEL for ATTR-CM so patients can receive timely access to this medicine.”

In 2011, a different form of VYNDAQEL, tafamidis meglumine 20 mg capsule, was approved in the EU for transthyretin amyloidosis in adult patients with stage 1 symptomatic polyneuropathy (ATTR-PN) to delay peripheral neurologic impairment. For ATTR-CM, the tafamidis 61 mg capsule corresponds to an 80 mg tafamidis meglumine dose (4x 20mg capsules) and was developed for patient convenience to enable a single capsule for daily administration.

The European line extension application was based on the Phase 3 ATTR-ACT study, the first and only completed global, double-blind, randomised, placebo-controlled clinical trial to investigate a pharmacologic therapy for the treatment of ATTR-CM.5 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).5 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.5 The application is also based on findings from an evaluation of the free acid form of tafamidis 61 mg.6 The ATTR-ACT 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.

The CHMP’s opinion will now be reviewed by the EC and a final decision is expected in the coming months.

About ATTR Amyloidosis

ATTR amyloidosis is rare, progressive disease characterized by the abnormal buildup of amyloid deposits composed of misfolded transthyretin protein in the body’s organs and tissues. ATTR amyloidosis can impact numerous organs and tissues in the body, including the peripheral nervous system, and organs such as the heart, kidneys, gastrointestinal tract, and eyes. ATTR-CM and ATTR-PN are two presentations of the disease.

ATTR-CM affects the heart and leads to restrictive cardiomyopathy and progressive heart failure. There are two sub-types of ATTR-CM: hereditary, which is caused by a mutation in the transthyretin gene and can occur in people as early as their 50s and 60s; or the wild-type form which is associated with aging, and is thought to be more common, usually affecting men after age 60.7,8 Often ATTR-CM is diagnosed only after symptoms have become severe. Once diagnosed, the median life expectancy in patients with ATTR-CM, dependent on sub-type, is approximately two to 3.5 years.4

ATTR-PN results from a genetic mutation of the transthyretin gene, amyloid fibrils form in the peripheral and autonomic nerves. ATTR-PN typically occurs during active adult years with onset as early as the 30s in some patients, followed by disease progression that may reach the terminal stage in approximately 10 years on average from disease onset.

About VYNDAQEL® (tafamidis 61 mg) and VYNDAQEL® (tafamidis meglumine 20 mg) 1,6

VYNDAQEL (tafamidis 61 mg) and VYNDAQEL (tafamidis meglumine 20 mg) are oral transthyretin stabilizers that selectively bind to transthyretin, stabilizing the tetramer of the transthyretin transport protein and slowing the formation of amyloid that causes ATTR-CM.

The tafamidis 61 mg capsule corresponds to an 80 mg tafamidis meglumine dose (4x 20mg capsules) and was developed for patient convenience to enable a single capsule for daily administration. VYNDAQEL 61 mg and VYNDAQEL 20 mg are not substitutable on a per milligram basis.

Tafamidis was granted Orphan Drug Designation for ATTR-CM in both the EU and US in 2012 and in Japan in 2018. Tafamidis was approved in Japan under SAKIGAKE designation for the treatment of ATTR-CM in March 2019, in the United States in May 2019, and in the United Arab Emirates in November 2019.

VYNDAQEL (20 mg) was first approved in 2011 in the EU for the treatment of transthyretin amyloid polyneuropathy (ATTR-PN), in adult patients with stage 1 symptomatic polyneuropathy to delay peripheral neurologic impairment. Currently, it is approved for ATTR-PN in 45 countries, including Japan, countries in Europe, Brazil, Mexico, Argentina, Israel, Russia, and South Korea.

VYNDAQEL has not received marketing authorisation for patients with ATTR-CM in the EU.

Pfizer Rare Disease

Rare disease includes some of the most serious of all illnesses and impacts millions of patients worldwide, 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.

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.

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References

1 Rapezzi C, Lorenzini M, Longhi S, et al. Cardiac amyloidosis: the great pretender. Heart Fail Rev. 2015;20(2):117-124.

2 Ando Y, Coelho T, Berk JL, et al. Guideline of transthyretin-related hereditary amyloidosis for clinicians. Orph J of Rare Diseases. 2013;8:31.

3 Rapezzi C, Quarta CC, Riva L, et al. Transthyretin related amyloidoses and the heart: a clinical overview. Nat Rev Cardiol. 2010;7:398-408.

4 Castano A, Drachman BM, Judge J, et al. Natural history and therapy of TTR-cardiac amyloidosis: emerging disease-modifying therapies from organ transplantation to stabilizer and silencer drugs. Heart Fail Rev. 2015; 20(2): 163–178. doi:10.1007/s10741-014-9462-7.

5 Maurer MS, Schwartz JH, Gundapaneni B, et al. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med. 2018;379(11):1007-1016.

6 Data on file. Pfizer Inc. New York, NY.

7 Connors LH, Sam F, Skinner M, et al. Heart failure due to age-related cardiac amyloid disease associated with wild-type transthyretin: a prospective, observational cohort study. Circulation. 2016;133(3):282-290.

8 Swiecicki PL, Zhen DB, Mauermann ML, et al. Hereditary ATTR amyloidosis: a single-institution experience with 266 patients. Amyloid. 2015;22(2):123-131.

SOURCE: Pfizer