Pfizer Receives Positive CHMP Opinion for VYNDAQEL® (tafamidis) for Use in Patients with Transthyretin Amyloid Cardiomyopathy, a Rare and Fatal Disease

-If approved by the European Commission (EC), tafamidis will be the first pharmacologic therapy in the EU for patients with transthyretin amyloid cardiomyopathy-

Pfizer Ltd, Walton Oaks, UK – 13 December 2019: Pfizer Ltd 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).1  

“The CHMP positive opinion for tafamidis marks an important step forward in helping people living with ATTR-CM, a rare and fatal heart disease, who to date have had no effective treatment options available to them,” said Owen Marks, Head of Rare Diseases at Pfizer UK, “Pfizer is committed to investing in and supporting people living with this rare and fatal form of heart disease.” 

ATTR-CM is a rare, life-threatening disease characterised by the buildup of abnormal deposits of misfolded protein called amyloid in the heart and is defined by restrictive cardiomyopathy and progressive heart failure.2,3,4 On average, patients live only 2 to 3.5 years following diagnosis.5  

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.6 In the primary analysis of the study, 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).6 Additionally, individual components of the primary analysis demonstrated a relative reduction in the risk of all-cause mortality and frequency of cardiovascular-related hospitalisation of 30% (p=0.026) and 32% (p<0.0001), respectively, with tafamidis versus placebo, with a relative risk ratio of 0.68 (0.48 per year vs. 0.70 per year;95% CI, 0.56 to 0.81).  6 The application is also based on findings from an evaluation of the free acid form of tafamidis 61 mg.7 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 European Commission and a final decision is expected in the coming months. 

About ATTR Amyloidosis 

ATTR amyloidosis is rare, progressive disease characterised 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 transthyretin amyloid polyneuropathy (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 60.8,9 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.5 

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)2,7

Tafamidis 61 mg and tafamidis meglumine 20 mg are oral transthyretin stabilisers that selectively bind to transthyretin, stabilising 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 20 mg capsules) and was developed for patient convenience to enable a single capsule for daily administration. Tafamidis 61 mg and tafamidis 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 ATTR-PN, in adult patients with stage 1 symptomatic polyneuropathy to delay peripheral neurologic impairment. Currently, it is approved for ATTR-PN in 40 countries, including Japan, countries in Europe, Brazil, Mexico, Argentina, Israel, Russia, and South Korea. 

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

Pfizer Rare Disease

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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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DISCLOSURE NOTICE: The information contained in this release is as of December 13, 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 in the EU for Vyndaqel for the treatment of wild-type or hereditary transthyretin amyloidosis in adult patients with 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 endpoints, commencement and/or completion dates for our clinical trials, regulatory submission dates, regulatory approval dates and/or launch dates, as well as the possibility of unfavorable new clinical data and further analyses of existing clinical data; the risk that clinical trial data are subject to differing interpretations and assessments by regulatory authorities; 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 EMA may approve the pending application for tafamidis for the Potential Indication and whether and when regulatory authorities in any such other jurisdictions where applications for tafamidis may be pending  or filed for the Potential Indication or any other potential indications for tafamidis may approve any such applications, which will depend on myriad factors, including making a determination as to whether the product’s benefits outweigh its known risks and determination of the product’s efficacy and, if approved, whether tafamidis will be commercially successful; decisions by regulatory authorities impacting labeling, manufacturing processes, safety and/or 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, 2018 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 Vyndaqel (tafamidis) Committee for Medicinal Products for Human Use (CHMP). https://www.ema.europa.eu/en/documents/smop/chmp-post-authorisation-summary-positive-opinion-vyndaqel-x-49g_en.pdf  Date accessed December 2019.   2 Rapezzi C, Lorenzini M, Longhi S, et al. Cardiac amyloidosis: the great pretender. Heart Fail Rev. 2015;20(2):117124. 3 Ando Y, Coelho T, Berk JL, et al. Guideline of transthyretin-related hereditary amyloidosis for clinicians. Orph J of Rare Diseases. 2013;8:31.   

4 Rapezzi C, Quarta CC, Riva L, et al. Transthyretin related amyloidoses and the heart: a clinical overview. Nat Rev Cardiol. 2010;7:398-408. 5 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. 6 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. 7 Tankisheva E. A phase 1, open-label, randomized, crossover, multiple dose, pivotal bioequivalence study to compare PF-06291826 4 × 20 mg tafamidis meglumine and 61 mg: tafamidis free acid soft gelatin capsules administered under fasted conditions to healthy volunteers. Full Clinical Study Report [protocol B3461056]. July 23, 2018.  8 Connors LH, Sam F, Skinner M, et al. Heart failure due to age-related cardiac amyloid disease associated with wildtype transthyretin: a prospective, observational cohort study. Circulation. 2016;133(3):282-290. 9 Swiecicki PL, Zhen DB, Mauermann ML, et al. Hereditary ATTR amyloidosis: a single-institution experience with 266 patients. Amyloid. 2015;22(2):123-131.