A few years ago, a 50-year-old man visited a hospital when he experienced shortness of breath and edema. But he had to visit a number of hospitals for years for examination as he struggled to pin point the name of the disease.

And one day, he felt tingling sensation in his toes and examined the heart. That was the time he had to face his rare disease called hereditary transthyretin amyloid cardiomyopathy (ATTR-CM).

Typically categorized as either wild type or hereditary, ATTR-CM is an ultra rare disease that has extremely limited patient size and the prevalence rate in South Korea has not been estimated. To this date, about over 120 types of genetic mutation have been reported, and apparently some of them show qualities of endemic disease in specific regions.

But the biggest issue is that the disease is easily diagnosed as other disease.

Some of the major symptoms of ATTR-CM include congestive heart failure, shortness of breath, edema, fatigue and more. And because of these symptoms, the rare disease is often misdiagnosed as unexpected restrictive cardiomyopathy, heart failure, irregular heartbeat and heart failure with preserved ejection fraction (HFpEF).

According to the researches done by academic societies so far, ATTR-CM is identified as a critical advanced rare disease resulting in restrictive cardiomyopathy caused by extracelluar deposition of transthyretin (TTR), normally involved in the transportation of the hormone thyroxine and retinol-binding protein, in the myocardium

Moreover, these patients’ prognosis could be worsened rapidly due to accumulated amyloid, and in fact, the survival period from the point of diagnosis is only about two to 3.5 years.

Considering the dire conditions, experts reiterate “An accurate early diagnosis is crucial for adequate disease management and improved treatment in patients with ATTR-CM.”

ATTR-CM treatment manages heart failure and irregular heartbeat, and uses treatments”

Even for ATTR-CM treatment scene with an absence of adequate treatment, a new door to treatment option was opened from August.

For the South Korean market, Vyndamax (tafamidis) is now indicated to treat adult patients with ATTR-CM based on its evidence of reducing the risk of heart-related death and cardiovascular issue-related hospitalization. The drug is the first and only treatment for the disease in South Korea.

The American Heart Association (AHA) recommends three treatment types for ATTR-CM—managing heart failure and irregular heartbeat, and using treatments.

Before the new indication approval, the only treatment was to manage the organ failure symptoms and to slow down the disease progress.

But ultimately, Vyndamax became a breakthrough treatment that patients can expect to reduce risk of cardiovascular-related death or hospitalization as the health authority cleared the drug.

The U.S. Food and Drug Administration (FDA) approved the treatment for patients with wild type or hereditary ATTR-CM, and more specifically the patients categorized as New York Heart Association (NYHA) Heart Failure Class I through III. The U.S. health authority reflected the recommendation of the drug contributing in delaying the disease progress when consuming Vyndamax at early stage.

Also, the Summary of Product Characteristics on tafamidis, published by the European Medicines Agency (EMA) mentions “To seek for more accurate clinical benefit in progress of ATTR-CM, tafamidis treatment should be initiated as soon as possible.”

Rate of misdiagnosis high in South Korea and delays actual treatment

The approval on Vyndamax was based on the results of a multicenter, placebo-controlled Phase III ATTR-ACT study with 441 patients with ATTR-CM.

The 441 patients were randomly assigned to administrating 80 mg or 20 mg of tafamidis or placebo. The primary endpoint evaluated the frequency of cardiovascular related death and hospitalization.

The secondary endpoint was the change in the Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) score from 6-minute walk test taken and compared among the baseline time to 30-month point.

The study found 264 people, who were administered with two different doses of tafamidis, had 29.5 percent and 42.9 percent lower risk of death by all causes, respectively, than the 177 in the placebo group and the risk of hospitalization also improved statically.

Moreover, the KCCQ-OS score and the 6-minute walk test at the 30-month point were improved significantly with the drug.

The president of the Korean Society of Heart Failure and a cardiology professor at Seoul National University Bundang Hospital, Dr. Choi Dong-ju emphasized, “ATTR-CM has high rate of misdiagnosis, which usually delays the diagnosis process. The ATTR-CM patients tend to only survive at least two to 3.5 years after the diagnosis, so an early diagnosis and aggressive treatment are important.”

Dr. Choi elaborated, “Although the studies and investigation on the disease is insufficient in South Korea, an effective treatment Vyndamax is already approved for prescription. If the patients can quickly get diagnosed, they would be able to manage their prognosis better. But because the drug is not listed for reimbursement, the financial burden on ATTR-CM patients in Korea is unfortunately very high. I hope the treatment access improve even by a bit as the disease has to be both urgently diagnosed and treated.”

Regardless of all efforts by the government and other organization, the only treatment option Vyndamax is still not listed for reimbursement in South Korea.