Transthyretin-Mediated Amyloidosis (ATTR-CM); After Nine Years Pfizer Wins FDA Breakthrough Designation

It has been nine years since Pfizer acquired the drugs vyndagel and vyndamax. According to a report in Biospace, based on the FDA’s recent approval of the two drugs to treat transthyretin-mediated amyloidosis (ATTR-CM), analysts predict a huge success that could amount to almost two billion dollars in sales.

VYNDAQEL®  (tafamidis meglumine) and VYNDAMAX™(tafamidis) are the only drugs FDA approved to treat ATTR-CM. Transthyretin transports cerebrospinal fluid carrying thyroxine, a thyroid hormone, and a retinol-binding protein. Thyroxine is a hormone that is produced by the thyroid gland that regulates development and growth.

About Transthyretin-Mediated Amyloidosis (ATTR-CM)

ATTR-CM is a rare disease that is defined by the accumulation of damaged (misfolded) proteins called amyloid deposited in the heart.

To date, researchers have identified over 120 amyloidogenic mutations. ATTR-CM is characterized as restrictive cardiomyopathy (disease of the heart muscle) or progressive heart failure. Approximately fifty thousand people, ranging in age from thirty to seventy, are affected worldwide.

The symptoms of ATTR-CM resemble many common disorders.  Therefore it is difficult to diagnose. Patients are often seen by multiple specialists before receiving a final, accurate diagnosis. In many cases, patients are misdiagnosed and are treated for conditions unrelated to ATTR-CM. Unfortunately, ATTR-CM is too often diagnosed when the symptoms have become severe.

Prior to the FDA approval of VYNDAQEL and VYNDAMAX,  ATTR-CM patients had to rely on symptom management and in some cases heart and liver transplants.

ATTR-CM Sub-types

The first of the two ATTR-CM sub-types is hereditary or also called “variant”. This sub-type can occur in people fifty years of age or older. The known cause is a mutation in the transthyretin gene.

The second sub-type is more common. It is associated with the aging process and generally affects men sixty years of age or older. It is called the “wild-type” form.

FDA Breakthrough Designation

FDA Breakthrough therapy is not final approval. The designation expedites the development of drugs to treat a serious condition based on evidence that the drug will be a substantial improvement over existing therapy.

In the case of VYNDAQEL and VYNDAMAX, Pfizer was awarded the designation based on the outcome of its cardiovascular trial, ATTR-ACT.

In 2012, Orphan Drug Designation for ATTR-CM was awarded to VYNDAQEL in the EU, in the United States and eventually in Japan.

Orphan Drug Designation is awarded for drugs that are proven to be safe and effective in the treatment of rare diseases that affect less than 200,000 people.

VYNDAQEL was given Priority Review by the FDA in 2018 for the NDA, (new drug application). This means that the FDA will review and act on the application in six months rather than the standard ten months.

Note that the two drugs were approved in rapid succession immediately following the FDA’s recent NDA review.

Transthyretin Amyloidosis Cardiomyopathy Clinical Trial (ATTR-ACT) 

The Phase 3 double-blind (treatment was unknown to doctors and patients) randomized study was placebo-controlled. A primary endpoint provided evidence that compared to a placebo, VYNDAQEL showed significant risk reduction. The end results, reviewed over a three-year period, highlighted a reduction in mortality by thirty percent. The treatment reduced the number of hospitalizations due to cardiovascular causes by thirty-two percent versus the placebo.

Although at this time no other drugs have been approved for ATTR-CM, drugs are now on the market and in various stages of development for somewhat similar diseases.


Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia (AML) six years ago. During this period of partial remission, Rose researched investigational drugs to be prepared in the event of a relapse. Her husband died February 12, 2021 with a rare and unexplained occurrence of liver cancer possibly unrelated to AML.

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