Evaluation of Mortality During Long-Term Treatment with Tafamidis for Transthyretin Amyloidosis with Polyneuropathy: Clinical Trial Results up to 8.5 Years

Abstract

Introduction: The effects of tafamidis on mortality in Val30Met and non-Val30Met patients with transthyretin amyloidosis with polyneuropathy (ATTR-PN) were evaluated. Methods: The analyses were based on cumulative data from the Val30Met patients in the 18-month double-blind registration study and its 12-month open-label extension study, the non-Val30Met patients of the 12-month openlabel study, and both patient groups in the ongoing 10-year extension study. Kaplan-Meier analyses of time to death from first treatment dose were performed. For the Val30Met group, two treatment groups were analyzed: those who received tafamidis in both the parent and extension studies (T-T) and those who received placebo in the parent study and switched to tafamidis in the extension studies (P-T). Results: Kaplan-Meier estimates (95% confidence interval [CI]) were available up to 9 years for the Val30Met group, at which time 85.9% (53.1-96.4) and 91.1% (77.9-96.6) of the patients in the T-T and P-T groups, respectively, were alive. For the non-Val30Met group, estimates were available up to 8 years from the first dose, and the percentage of patients alive was 75.9% (47.7-90.2). Conclusion: Long-term tafamidis treatment may confer survival benefit in patients with ATTR-PN.

Real-world outcomes in non-endemic hereditary transthyretin amyloidosis with polyneuropathy: a 20-year German single-referral centre experience

“…In several clinical trials, the TTR kinetic stabilising oral drug tafamidis meglumine, approved in a dosage of 20 mg qd for the treatment of stage 1 ATTRv-PN, demonstrated a significant slowdown of neurologic and cardiologic aspects of the disease course [11][12][13][14][15], which recently led to the approval of tafamidis also for ATTR-related cardiomyopathy in a higher dosage of 61 mg qd. Notwithstanding the convincing therapeutic effects of two innovative TTR gene silencing medications, the antisense oligonucleotide inotersen [16] and the small interfering RNA patisiran [17], and their subsequent approval for ATTRv-PN stages 1 and 2 [2], tafamidis has been the only approved medication to be in in-label use for almost 10 years to date for which long-term experiences outside controlled clinical trials can reliably be evaluated.…”

Advances in Treatment of ATTRv Amyloidosis: State of the Art and Future Prospects

“…Disease severity, sex, and TTR concentration at the beginning of therapy were the most relevant predictors of response [ 32 ]. However, mortality data emerged in a recent study showed that approximately 85% of V30M patients and 75% of non-V30M patients were alive after 9 and 8 years of treatment with tafamidis, respectively (11 and 14 years after disease onset, respectively) [ 33 ]. This outcome is very encouraging, considering that life expectancy in untreated patients is about 10 years [ 34 ].…”

Use of Drugs for ATTRv Amyloidosis in the Real World: How Therapy Is Changing Survival in a Non-Endemic Area

“…To date, some studies on the efficacy of new drugs in modifying the outcomes of patients over short periods have been performed, but information on survival is lacking, mainly in non-V30M patients [ 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. A recent paper showed that in non-endemic late-onset ATTRv amyloidosis, long-term treatment with tafamidis is safe and efficacious, and the severity of polyneuropathy at the start of treatment is the main predictor for disease progression on tafamidis [ 30 ].…”