Tafamidis meglumine safely slows FAP progression: Brazil study
Real-world study tracks data from clinical trials, researchers say
Tafamidis meglumine safely and effectively slows disease progression in most people living with familial amyloid polyneuropathy (FAP), according to a real-world study from Brazil. The findings were in line with data from clinical trials.
“The efficacy and safety of tafamidis reported in clinical trials is expandable to the Brazilian real-world scenario,” the researchers wrote.
This is particularly important for patients in Brazil, where tafamidis meglumine — approved as Vyndaqel for FAP in Brazil, Europe, but not the U.S. — is the only FAP therapy covered by the country’s public health system.
The study, “Real-world tafamidis experience in hereditary transthyretin amyloidosis with peripheral neuropathy in Brazil,” was published in the journal Arquivos de Neuro-Psiquiatria.
Also known as hereditary transthyretin amyloid with polyneuropathy (ATTRv-PN), FAP is caused by genetic mutations that result in an unstable version of a protein called transthyretin (TTR). This abnormal protein is prone to misfolding and forming toxic clumps, known as amyloid deposits, mostly in peripheral nerves (those that run outside the brain and the spinal cord). The buildup causes damage and results in FAP symptoms like numbness, tingling, and weakness.
Stabilizing transthyretin
Pfizer’s tafamidis meglumine is an oral therapy that stabilizes transthyretin, preventing it from forming toxic clumps, slowing disease progression. It is approved to treat FAP in Europe, South America, and Asia, but not the U.S.
The team of researchers in Brazil set out to determine whether tafamidis meglumine is as safe and works as well in real-world settings as it did in clinical trials in which patients’ nerve function improved or didn’t worsen with the therapy.
Clinical trials are done in controlled conditions and on subsets of patients with specific criteria, so it is key to confirm a therapy’s safety and efficacy in real-world settings where patients may have varying conditions or receive different levels of care.
The researchers retrospectively reviewed the medical records of 33 patients who were started on tafamidis meglumine at a Brazilian medical center from September 2011 to March 2022. They only looked at patients who had at least one follow-up visit six months after starting treatment.
Patients had a median age of 40 at treatment start, and 18 (55%) were women. Most (61%) had early-onset FAP, meaning symptoms began to manifest before age 50, while 39% had late-onset FAP, with symptoms having first manifested when they were 50 or older. All carried Val30Met, the most common FAP-causing genetic mutation.
Three of the patients had been previously treated with Tegsedi (inotersen), another approved FAP therapy, and switched to tafamidis meglumine due to side effects.
Patients were followed for a mean of 3.4 years.
Results showed that most patients (75.8%) responded to tafamidis meglumine. The remaining eight (24.2%) were considered non-responders, meaning they experienced a yearly increase of seven or more points on the Neuropathy Impairment Score (NIS) from treatment start. In the NIS, a measure of nerve damage-related disability, a higher score indicates more severe symptoms.
While the group of responders had similar demographic and clinical features to non-responders at study’s start, the median NIS progression rate per year with tafamidis meglumine was of 0 points in responders and 11.3 points in non-responders, “which is similar to the expected rate of progression in untreated patients,” the researchers wrote.
By the last follow-up visit, most patients (69.7%) had a stable polyneuropathy disability (PND) stage, which is based mainly on how walking is affected.
Neurological impairment and disability had slightly worsened in the overall patient population. However, nerve conduction test results, which measure how well nerves function, remained stable. The findings were similar between patients with early-onset FAP and those with late-onset disease.
No patients discontinued the therapy to undergo liver transplant, and there were no deaths during the study. No adverse events were deemed related to tafamidis meglumine.
“For being safe, cheaper, and effective, tafamidis still has an important role in the treatment of ATTRv-PN, especially in very early stages,” and, as an oral treatment, “it has the benefit of being easy to manage by patients and doctors,” the researchers wrote.
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