These results support data from clinical trials showing that Vyndaqel is an effective treatment for FAP.
The study, “Positive Effectiveness of Tafamidis in Delaying Disease Progression in Transthyretin Familial Amyloid Polyneuropathy up to 2 Years: An Analysis from the Transthyretin Amyloidosis Outcomes Survey (THAOS),” was published in the journal Neurology and Therapy.
FAP is a rare disorder caused by mutations in the TTR gene — a gene that provides instructions to produce a protein called transthyretin. TTR mutations lead to an unstable protein structure, and to the formation and accumulation of toxic amyloid aggregates in peripheral nerves and organs.
Among the more than 100 different TTR gene mutations associated with FAP, Val30Met is the most common. Patients with non-Val30Met mutations have been recognized as having poorer outcomes.
Vyndaqel, developed by Pfizer, is an approved therapy for FAP in the European Union and in several countries in Latin America and Asia. Vyndaqel is not currently approved in the U.S., but it is being evaluated as a treatment for TTR-associated heart disease, called familial amyloid cardiomyopathy (FAC).
Vyndaqel prevents the formation of the toxic amyloid aggregates by stabilizing the TTR protein.
Previous clinical trials have shown that Vyndaqel is a safe and effective treatment for FAP patients with the Val30Met mutation or with other mutations. However, little is known about Vyndaqel’s real-world effectiveness.
To evaluate the effectiveness of Vyndaqel for the treatment of FAP in a real-world setting, researchers conducted an observational study (NCT00628745) that analyzed data from the Transthyretin Amyloidosis Outcomes Survey (THAOS) registry — the largest international registry collecting data of patients with FAP and other TTR-associated diseases.
The study included data from 274 patients treated with Vyndaqel and 255 untreated patients in a control group. The data from each treated individual was compared with data from up to four untreated patients, who had the same type of mutation, country of birth, and probability of receiving treatment.
Most patients treated with Vyndaqel had the Val30Met mutation (92.5%), were from Portugal (80.2%), and were relatively young, with a mean age of 40.4 years. Median follow-up time was 23.6 months for treated subjects and 21.4 months for untreated subjects.
Vyndaqel treatment significantly delayed nerve cell disease progression and deterioration in quality of life compared with untreated patients. No effects on functional impairment or nutritional status were observed.
Although the survival analysis of matched patients was not able to produce estimates on the risk of death — as no treated patient died — a secondary analysis comparing all patients (unmatched) showed that untreated individuals had a greater risk of death than treated patients.
“These findings confirm previous results and provide evidence for the effectiveness of tafamidis outside conventional clinical trials,” the researchers wrote.
The team noted that due to the characteristics of the studied population, these findings may not be generalized to patients with non-Val30Met mutations or late-onset Val30Met FAP. Further studies are needed to understand Vyndaqel’s effects in those patients in a real-world setting.