Abstract 15528: Tafamidis Free Acid 61 Mg in Patients With Transthyretin Amyloid Cardiomyopathy

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Jose Nativi-Nicolau ◽  
peter van der meer ◽  
Balarama Gundapaneni ◽  
Marla B Sultan ◽  
Pablo Garcia-Pavia
Keyword(s):  
Free Acid ◽  
Early Stage ◽  
System Organ Class ◽  
Transthyretin Amyloidosis ◽  
Cardiac Disorders ◽  
Amyloid Cardiomyopathy ◽  
New Formulation ◽  
System Organ

Introduction: Tafamidis meglumine, available as 20 mg capsules, is approved around the world for the treatment of transthyretin amyloidosis in early stage polyneuropathy (20 mg) and more recently in cardiomyopathy (80 mg). A new formulation, tafamidis free acid 61 mg (a single capsule bioequivalent to tafamidis meglumine 80 mg), was subsequently developed as a more convenient option for patients with transthyretin amyloid cardiomyopathy (ATTR-CM) and further characterization of its safety profile would be of value. Methods: Patients who completed the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) were eligible to enroll in a long-term, extension study (LTE). The LTE was subsequently expanded to include ATTR-CM patients not previously enrolled in ATTR-ACT, with all patients receiving tafamidis free acid 61 mg (tafamidis 61 mg). As of 20 July, 2018, patients in the LTE were transitioned to tafamidis free acid 61 mg (data assessed for patients treated with tafamidis 80 mg in the LTE who transitioned to tafamidis free acid 61 mg [tafamidis 80/61 mg]). Adverse events (AEs) during the LTE are described (as of 1 Aug, 2019) and compared with AEs with tafamidis 80 mg in ATTR-ACT. Results: There were 164 patients treated with tafamidis 80/61 mg and 715 newly enrolled patients treated with tafamidis 61 mg; with 157 (95.7%) AEs with tafamidis 80/61 mg and 458 (64.1%) with tafamidis 61 mg. The most common AEs by system organ class were cardiac disorders ( Table ). AEs with tafamidis 80/61 mg were broadly similar to those with tafamidis 80 mg in ATTR-ACT (previously shown to be similar to placebo). While there were fewer AEs with tafamidis 61 mg, the notably shorter exposure time in this group limits direct comparisons. Nevertheless, no new safety concerns emerged in patients who transitioned to, or started, tafamidis 61 mg. Conclusions: For patients with ATTR-CM, tafamidis free acid 61 mg is a safe treatment which also offers improved patient convenience.

Abstract 12896: Safety of Transition From Tafamidis Meglumine 20 Mg to Tafamidis Free Acid 61 Mg in Patients With Transthyretin Amyloid Cardiomyopathy

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Thibaud Damy ◽  
Nowell Fine ◽  
Balarama Gundapaneni ◽  
Marla B Sultan ◽  
Martha Grogan
Keyword(s):  
Free Acid ◽  
Early Stage ◽  
System Organ Class ◽  
Transthyretin Amyloidosis ◽  
Safety Concerns ◽  
Daily Dose ◽  
Amyloid Cardiomyopathy ◽  
System Organ ◽  
Similar Incidence

Introduction: Tafamidis meglumine, available as 20 mg capsules, is approved in >40 countries for use in early stage, symptomatic transthyretin amyloidosis with polyneuropathy. It is also approved in a growing number of countries as an 80 mg daily dose (4 x 20 mg capsules) and as tafamidis free acid 61 mg (a single dose bioequivalent to tafamidis meglumine 80 mg) for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM). As some patients receiving tafamidis meglumine 20 mg may benefit from transition to tafamidis free acid 61 mg, we assessed the hypothesis that this transition is not associated with any new safety concerns. Methods: In the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) patients with ATTR-CM were treated with tafamidis meglumine 20 mg, 80 mg, or placebo for up to 30 months. Patients completing the trial could enroll in a long-term extension study (LTE) with placebo-treated patients randomized to tafamidis meglumine 20 mg or 80 mg. All patients in the LTE were later transitioned to tafamidis free acid 61 mg. Adverse events (AEs) emerging during the LTE were assessed in patients treated with tafamidis meglumine 20 mg in the LTE who transitioned to tafamidis free acid 61 mg (median exposure 19.8 months). AEs were compared with those emerging during ATTR-ACT in patients treated with tafamidis meglumine 20 mg (median exposure 29.7 months). Results: The 87 patients treated with tafamidis meglumine 20 mg in the LTE who transitioned to tafamidis free acid 61 mg had a similar incidence of the most common AEs by system organ class, and of specific AEs, as those treated with tafamidis meglumine 20 mg in ATTR-ACT (see Table ). The safety profile of tafamidis meglumine 20 mg was previously shown to be similar to placebo. Conclusions: While the duration of exposure to tafamidis free acid 61 mg was shorter than for tafamidis meglumine 20 mg, these data demonstrate that the transition to tafamidis free acid 61 mg is not associated with any new safety concerns.

scholarly journals Long-Term Survival With Tafamidis in Patients With Transthyretin Amyloid Cardiomyopathy

2021 ◽  
Author(s):  
Perry Elliott ◽  
Brian M. Drachman ◽  
Stephen S. Gottlieb ◽  
James E. Hoffman ◽  
Scott L. Hummel ◽  
...  
Keyword(s):  
New York ◽  
Free Acid ◽  
Heart Association ◽  
Class Iii ◽  
Unique Identifier ◽  
Transthyretin Amyloidosis ◽  
Term Survival ◽  
New York Heart Association ◽  
Amyloid Cardiomyopathy

Background: Tafamidis is approved in many countries for the treatment of transthyretin amyloid cardiomyopathy. This study reports data on the long-term efficacy of tafamidis from an ongoing long-term extension (LTE) to the pivotal ATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial). Methods: Patients with transthyretin amyloid cardiomyopathy who completed ATTR-ACT could enroll in an LTE, continuing with the same tafamidis dose or, if previously treated with placebo, randomized (2:1) to tafamidis meglumine 80 or 20 mg. All patients in the LTE transitioned to tafamidis free acid 61 mg (bioequivalent to tafamidis meglumine 80 mg) following a protocol amendment. In this interim analysis, all-cause mortality was assessed in patients treated with tafamidis meglumine 80 mg in ATTR-ACT continuing in the LTE, compared with those receiving placebo in ATTR-ACT transitioning to tafamidis in the LTE. Results: Median follow-up was 58.5 months in the continuous tafamidis group (n=176) and 57.1 months in the placebo to tafamidis group (n=177). There were 79 (44.9%) deaths with continuous tafamidis and 111 (62.7%) with placebo to tafamidis (hazard ratio, 0.59 [95% CI, 0.44–0.79]; P <0.001). Mortality was also reduced in the continuous tafamidis (versus placebo to tafamidis) subgroups of: variant transthyretin amyloidosis (0.57 [0.33–0.99]; P =0.05) and wild-type transthyretin amyloidosis (0.61 [0.43–0.87]; P =0.006); and baseline New York Heart Association class I and II (0.56 [0.38–0.82]; P =0.003) and class III (0.65 [0.41–1.01]; P =0.06). Conclusions: In the LTE, patients initially treated with tafamidis in ATTR-ACT had substantially better survival than those first treated with placebo, highlighting the importance of early diagnosis and treatment in transthyretin amyloid cardiomyopathy. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01994889 and NCT02791230.

Abstract 13149: Survival Benefit With Higher Dose Tafamidis in Patients With Hereditary and Wild-type Transthyretin Amyloid Cardiomyopathy

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Sanjiv J Shah ◽  
Balarama Gundapaneni ◽  
Marla B Sultan ◽  
Giampaolo Merlini
Keyword(s):  
Survival Benefit ◽  
Treatment Duration ◽  
Free Acid ◽  
Optimal Dose ◽  
Wild Type ◽  
All Cause Mortality ◽  
Amyloid Cardiomyopathy ◽  
New Formulation

Introduction: Tafamidis was shown to be an effective treatment for patients with both hereditary/variant (ATTRv) and wild-type (ATTRwt) transthyretin amyloid cardiomyopathy (ATTR-CM) in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT). The higher dose of tafamidis (80 mg) was shown to be the optimal dose and is approved for the treatment of ATTR-CM. We hypothesized that longer term follow up would further characterize the benefit of higher dose tafamidis. Methods: In ATTR-ACT, patients were randomized to tafamidis meglumine (80 mg or 20 mg) or placebo for 30 months. Patients who completed ATTR-ACT were eligible to enroll in a long-term extension study (LTE) in which placebo-treated patients were randomized to tafamidis 80 mg or 20 mg. As of 20 July, 2018, all patients in the LTE were transitioned to tafamidis free acid 61 mg (a new formulation bioequivalent to tafamidis 80 mg). All-cause mortality (as of 1 Aug, 2019) was assessed in patients treated with tafamidis 80 mg in ATTR-ACT and the LTE who transitioned to tafamidis free acid 61 mg (tafamidis 80/61 mg) compared with patients treated with placebo in ATTR-ACT who transitioned to tafamidis in the LTE (placebo/tafamidis). Results: There were 85 ATTRv patients (42 tafamidis 80/61 mg [median treatment duration 53.8 months]; 43 placebo/tafamidis [48.1 months]) and 268 ATTRwt patients (134 tafamidis 80/61 mg [51.7 months]; 134 placebo/tafamidis [51.6 months]).In ATTRv patients, there were 25 (59.5%) deaths with tafamidis 80/61 mg and 30 (69.8%) deaths with placebo/tafamidis; a 39.8% reduction in risk of all-cause mortality with tafamidis 80/61 mg (hazard ratio vs placebo/tafamidis [95% CI], 0.6020 [0.3473, 1.0435]; P=0.0706). In ATTRwt patients, there were 50 (37.3%) deaths with tafamidis 80/61 mg and 78 (58.2%) deaths with placebo/tafamidis; a 40.1% reduction in risk of all-cause mortality with tafamidis 80/61 mg (0.5992 [0.4186, 0.8577]; P=0.0051). Conclusions: While there were fewer ATTRv patients in the study, longer-term follow-up demonstrated similarly improved survival with higher dose tafamidis in both ATTRv and ATTRwt patients. These data further highlight the benefit of tafamidis (80 mg meglumine or 61 mg free acid) in all patients with ATTR-CM.

scholarly journals Long-term survival with tafamidis in patients with transthyretin amyloid cardiomyopathy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Damy ◽  
P Elliott ◽  
B Gundapaneni ◽  
S See Tai ◽  
M.B Sultan ◽  
...  
Keyword(s):  
Median Survival ◽  
Free Acid ◽  
Funding Source ◽  
Private Company ◽  
Heart Transplants ◽  
Term Survival ◽  
Long Term Survival ◽  
All Cause Mortality ◽  
Amyloid Cardiomyopathy

Abstract Background The Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT), demonstrated that tafamidis was an effective treatment for patients with transthyretin amyloid cardiomyopathy (ATTR-CM). Tafamidis, at an 80 mg daily dose, was subsequently approved in several countries for the treatment of ATTR-CM. Patients who completed ATTR-ACT were eligible to enroll in an ongoing long-term extension study (LTE) which provides additional data on the long-term efficacy of tafamidis. Purpose To assess the long-term benefit of tafamidis in patients with ATTR-CM and to determine median survival times with treatment. Methods Patients with ATTR-CM who completed ATTR-ACT (in which they were randomized to tafamidis meglumine 80 mg, 20 mg or placebo for 30 months) could enroll in the ongoing LTE in which patients continued to be treated with the same dose of tafamidis or, if previously treated with placebo, were randomized to tafamidis meglumine 80 mg or 20 mg. Tafamidis free acid 61 mg is a new formulation (bioequivalent to tafamidis meglumine 80 mg) developed for patient convenience and all patients in the LTE transitioned to tafamidis free acid 61 mg as of 1 Aug, 2018. All-cause mortality (with heart transplant or cardiac mechanical assist device [CMAD] implantation counted as death) was assessed using a Cox proportional hazards model (as of 1 Aug, 2019). Patients treated with tafamidis meglumine 80 mg in ATTR-ACT and the LTE who transitioned to tafamidis free acid 61 mg (tafamidis 80/61 mg) were compared with patients treated with placebo in ATTR-ACT who transitioned to tafamidis in the LTE (placebo/tafamidis). Results There were a total of 176 tafamidis 80/61 mg patients and 177 placebo/tafamidis patients. Median treatment duration was 51.9 months with tafamidis 80/61 mg and 51.4 months with placebo/tafamidis. With tafamidis 80/61 mg, there were 75 (42.6%) all-cause deaths; consisting of 67 (38.1%) deaths, 6 (3.4%) heart transplants, and 2 (1.1%) CMAD implantations. With placebo/tafamidis, there were 108 (61.0%) all-cause deaths; consisting of 102 (57.6%) deaths and 6 (3.4%) heart transplants. There was a significant reduction of 41.1% in the risk of all-cause mortality with tafamidis 80/61 mg compared with placebo/tafamidis (hazard ratio [95% CI], 0.5888 [0.4370, 0.7931]; P=0.0004). Median survival time with placebo/tafamidis was 35.8 months but was not reached with tafamidis 80/61 mg. Conclusions Treatment with tafamidis significantly improves long-term survival in patients with ATTR-CM. The comparatively poorer survival in patients treated with placebo in ATTR-ACT who transitioned to tafamidis in the LTE highlights the importance of early diagnosis and treatment. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): This study was sponsored by Pfizer.

ASSESSMENT OF KIDNEY FUNCTIONAL RESERVE ON THE BACKGROUND OF ANTI-AGGREGATE THERAPY IN CHRONIC KIDNEY DISEASE II-III STAGE

2020 ◽  
Vol 6 (1) ◽  
pp. 49-54
Author(s):  
Khabib Barnoev ◽  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Comparative Study ◽  
Early Stage ◽  
Raw Material ◽  
Functional Reserve ◽  
Functional Reserves ◽  
Term Administration ◽  
Antiaggregant Therapy

The article presents the results of a study to assess the functional reserve of the kidneys against the background of a comparative study of antiaggregant therapy dipyridamole and allthrombosepin in 50 patients with a relatively early stage of chronic kidney disease. Studies have shown that long-term administration of allthrombosepin to patients has resulted in better maintenance of kidney functional reserves. Therefore, our research has once again confirmed that diphtheridamol, which is widely used as an antiaggregant drug in chronic kidney disease, does not lag behind the domestic raw material allthrombosepin

Sign in / Sign up

Export Citation Format

Share Document