Long-term tafamidis meglumine slows FAP progression: Study
Real-world study in Japan shows treatment's safety, efficacy
Long-term oral treatment with tafamidis meglumine safely helped maintain nerve function, quality of life, nutritional status, and mobility in people living with familial amyloid polyneuropathy (FAP) in Japan, according to a real-world study.
“This study sheds lights on the real-world safety and efficacy of tafamidis in patients who could not have been enrolled in clinical trials because of the strict eligibility criteria,” the researchers wrote.
The study, “Real-world utilization patterns, safety, and efficacy of tafamidis in patients with hereditary transthyretin amyloidosis in Japan,” was published in Current Therapeutic Research.
In FAP, also known as hereditary transthyretin amyloid with polyneuropathy (ATTRv-PN), genetic mutations result in an unstable version of a protein called transthyretin (TTR) that’s prone to misfolding and to forming toxic clumps known as amyloid deposits.
These aggregates build up mainly in peripheral nerves, those that run outside the brain and the spinal cord, resulting in FAP symptoms like numbness, tingling, and weakness.
Study results in line with data from clinical trials
Pfizer’s tafamidis meglumine — approved under the brand name Vyndaqel to treat early-stage FAP in the European Union and in a number of other countries, but not in the U.S. — works by stabilizing TTR. This prevents the protein from misfolding and forming amyloid deposits, thereby slowing the progression of the disease.
While the therapy’s safety and efficacy were established in clinical trials, these studies have specific eligibility criteria that do not represent the whole patient population. Real-world studies, which better reflect the general patient population, are key to further understanding the effects of therapies.
Pfizer launched an observational, post-marketing surveillance study (NCT02146378) in Japan in November 2013 to assess the safety and efficacy of tafamidis meglumine for up to three years.
A total of 400 participants, 397 with a diagnosis of FAP, were included in the safety analysis. The other three patients had hereditary transthyretin amyloid with cardiomyopathy (ATTRv-CM), a FAP-related condition in which amyloid deposits build up in heart muscles and for which tafamidis meglumine is also approved. The efficacy analysis was limited to the 397 FAP patients.
Patients had a mean age of 61.5, and nearly two-thirds (65.5%) were men. More than half (57.3%) developed the disease at age 50 or older (late-onset FAP), and most were from areas not previously known for high rates of the disease (non-endemic areas).
About half of the patients (53%) took tafamidis meglumine for more than three years. Slightly more than one-third (36.3%) stopped the study early for reasons including side effects, changing hospitals, loss to follow-up, or lack of response to treatment.
Adverse events were reported in 14.5% of patients, and serious adverse events occurred in 3%. The most commonly reported adverse events included nausea, diarrhea, constipation, and signs of abnormal liver function.
“The safety profile of tafamidis was largely consistent with that obtained from previous research, and no new safety concerns were identified,” the researchers wrote.
Statistical analyses demonstrated that participants from non-endemic areas, those with moderate liver problems, and those requiring walking aids had a significantly higher risk of developing adverse events than those from endemic areas, without liver problems, and with unaffected walking skills.
“It was unclear whether the prevalence of [adverse events] was directly affected by the area (nonendemic vs. endemic), because clinical factors such as age at onset of [FAP] and genetic factors were different between the areas,” the researchers wrote.
Effectiveness was assessed through validated measures of nerve function, quality of life, nutritional status, and mobility. All these measures remained generally stable over the study period, with most participants maintaining their walking skills after treatment, and nearly half still being able to walk without walking aids.
“The findings suggest the ability of tafamidis to suppress the progression of [FAP],” the researchers wrote, adding that “the efficacy of tafamidis in this study was similar to that reported in other real-world studies.”
The data also indicated that late-onset FAP and cases arising “from nonendemic areas may be more prevalent in Japan than historically believed,” the researchers concluded.
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