Jeffrey H. Schwartz's research while affiliated with Pfizer and other places

Publications (25)

Article
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Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive, fatal disorder resulting from mutations in the transthyretin gene (ATTRv) or the deposition of denatured wild-type transthyretin (ATTRwt). Objectives Tafamidis is an effective treatment for ATTR-CM, this study aimed to determine whether there is a differential effect betwe...
Article
Full-text available
In the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial, tafamidis significantly reduced all-cause mortality and cardiovascular-related hospitalizations in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). ATTR-CM is associated with a significant burden of disease; further analysis of patient-reported quality of life will provid...
Article
Full-text available
Aims Tafamidis is an effective treatment for transthyretin amyloid cardiomyopathy (ATTR‐CM) in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR‐ACT). While ATTR‐ACT was not designed for a dose‐specific assessment, further analysis from ATTR‐ACT and its long‐term extension study (LTE) can guide determination of the optimal dose. M...
Article
Background Transthyretin cardiomyopathy (ATTR-CM) is an underdiagnosed, fatal disease caused by the deposition of transthyretin amyloid fibrils in the heart leading to heart failure (HF). It can be hereditary due to mutations in the TTR gene (ATTRm) or acquired (wild-type [ATTRwt]). Tafamidis is a selective transthyretin stabilizer which prevents t...
Article
Introduction Tafamidis was shown to be an effective treatment for transthyretin amyloid cardiomyopathy (ATTR-CM) in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT). Hypothesis While ATTR-ACT was not designed for a definitive assessment by dose, further analysis may assist determination of the optimal dose. Methods In ATTR-...
Article
Introduction In the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT), tafamidis reduced all-cause mortality and cardiovascular-related hospitalizations in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). ATTR-CM is associated with a significant burden of disease and tafamidis reduced the decline in health-related qua...
Article
Full-text available
Background: Tafamidis is approved in over 40 countries to delay neurologic progression in patients with transthyretin amyloid polyneuropathy (ATTR-PN). A comprehensive, integrated analysis of safety data from interventional, observational and surveillance studies of tafamidis in ATTR-PN patients was conducted. Methods: Safety data from all sponsore...
Article
Full-text available
Background: Emerging evidence suggests that several factors can impact disease progression in transthyretin amyloid polyneuropathy (ATTR-PN). The present analysis used longitudinal data from Val30Met patients participating in the tafamidis (selective TTR stabilizer) clinical development program to evaluate the impact of baseline neurologic severit...
Article
Introduction Transthyretin cardiomyopathy (ATTR-CM) is an underdiagnosed, fatal disease caused by the deposition of transthyretin amyloid fibrils in the heart leading to heart failure (HF). It can be hereditary due to mutations in the TTR gene (ATTRm) or acquired (wild-type [ATTRwt]). Tafamidis is a selective transthyretin stabilizer which prevents...
Article
Background Transthyretin amyloid cardiomyopathy is caused by the deposition of transthyretin amyloid fibrils in the myocardium. The deposition occurs when wild-type or variant transthyretin becomes unstable and misfolds. Tafamidis binds to transthyretin, preventing tetramer dissociation and amyloidogenesis. Methods In a multicenter, international,...
Article
Full-text available
Background: To better characterize the effects of tafamidis in non-Val30Met patients with transthyretin familial amyloid polyneuropathy, this post-hoc analysis compared the neurologic results from a 12-month, open-label study of non-Val30Met vs. Val30Met patients at Month 12 from the 18-month, double-blind, placebo-controlled registration study. A...
Article
Full-text available
Background Transthyretin cardiomyopathy (TTR-CM) is a progressive, fatal disease caused by the accumulation of misfolded transthyretin (TTR) amyloid fibrils in the heart. Tafamidis is a kinetic stabilizer of TTR that inhibits misfolding and amyloid formation. Methods In this post hoc analysis, data from an observational study (Transthyretin Amyloi...
Article
Transthyretin amyloidosis is a rare, life-threatening disease resulting from aggregation and deposition of transthyretin amyloid fibrils in various tissues. There are 2 predominate phenotypic presentations of the disease: transthyretin familial amyloid polyneuropathy, which primarily affects the peripheral nerves, and transthyretin cardiomyopathy (...
Article
Full-text available
Background: Tafamidis, a non-NSAID highly specific transthyretin stabilizer, delayed neurologic disease progression as measured by Neuropathy Impairment Score–Lower Limbs (NIS-LL) in an 18-month, double-blind, placebo-controlled randomized trial in 128 patients with early-stage transthyretin V30M familial amyloid polyneuropathy (ATTRV30M-FAP). The...
Article
Full-text available
Transthyretin hereditary amyloid polyneuropathy, also traditionally known as transthyretin familial amyloid polyneuropathy (ATTR-FAP), is a rare, relentless, fatal hereditary disorder. Tafamidis, an oral, non-NSAID, highly specific transthyretin stabilizer, demonstrated safety and efficacy in slowing neuropathy progression in early-stage ATTRV30M-F...
Article
Full-text available
Objective: The purpose of this study was to evaluate the short- and long-term efficacy and safety of ziprasidone in children and adolescents with bipolar I disorder. Methods: Subjects 10-17 years of age with a manic or mixed episode associated with bipolar I disorder participated in a 4 week, randomized, double-blind, placebo-controlled multicen...
Article
Objective: The purpose of this study was to evaluate the short- and long-term efficacy, safety, and tolerability of ziprasidone in adolescents with schizophrenia. Methods: Subjects ages 13-17 years with schizophrenia (American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. [DSM-IV]) were enrolled in a 6 w...
Article
Background Ziprasidone, adjunctive to either lithium or valproate, has previously been shown to be associated with a significantly lower risk of relapse in bipolar disorder compared with lithium or valproate treatment alone.Methods This placebo-controlled outpatient trial with ziprasidone adjunctive to lithium or valproate or lithium and valproate...
Article
To assess efficacy and safety of adjunctive ziprasidone in subjects with bipolar depression treated with lithium, lamotrigine, or valproate. 298 adult outpatients with bipolar I disorder (DSM-IV criteria) were randomized to receive ziprasidone, 20-80 mg twice a day, or placebo twice a day for 6 weeks plus their preexisting mood stabilizer. The prim...
Article
To evaluate the efficacy and safety of ziprasidone adjunctive to a mood stabilizer for the maintenance treatment of bipolar mania. Subjects with DSM-IV bipolar I disorder with a Mania Rating Scale score > or = 14 were enrolled. Subjects achieving > or = 8 consecutive weeks of stability with open-label ziprasidone (80-160 mg/d) and lithium or valpro...

Citations

... The Kansas City Cardiac Questionnaire (KCCQ) is an objective, standardized measure recognized by regulatory bodies and familiar to cardiologists. Data specifically in AL cardiac amyloidosis is not available, but in ATTR cardiac amyloidosis, tafamidis was associated with better scores on KCCQ-12 than placebo, 65 and the instrument performed well in transthyretin cardiac amyloidosis (ATTR-CA) trials. 30 A 5-point change is considered the MCID; meaningful thresholds of 5, 10, and 20 points represent small, moderate-to-large, and large-to-very large clinical changes. ...
... Although not curative in all patients it represents very important progress in modifying the natural history of a disease considered almost incurable until a few years ago. A second very promising and innovative approach uses the silencing of the expression of pathogenic protein through the deployment of oligonucleotide technology [4] or, as recently reported for the first time directly in patients, through the use of CRISPR-CAS9 gene silencing technology [5]. Knocking out the expression of the pathogenic protein has been made possible by the extraordinary progress in our capacity to safely manipulate genes in vivo over the last twenty years. ...
... The ATTR-ACT study was not designed to compare the different therapeutic doses of the drug (80 vs. 20 mg): tafamidis 80 mg reduced the relative risk of mortality by 30% compared with the 20 mg dose with a concomitant reduction in NT-proBNP and without any change on the safety outcome. 10 Follow-up data up to 58 months were recently published, not only tafamidis therapy continued to provide a survival benefit over placebo, but this was also evident in patients with more advanced disease. First, the curves of NYHA III patients who initially did not have a benefit in the ATTR-ACT also began to diverge in a statistically significant manner with a longer follow-up. ...
... For example, in a list of Food and Drug Administration (FDA) approved drugs in 2020, there were no new drug approved for the treatment of CVD, which encompass more than half of all CVDs (U.S. Food and Drug Administraion (FDA), 2020). Only one drug was approved in 2019 for cardiomyopathy (Berk et al., 2020), and one drug approved in 2020 for hypercholesterolemia (Markham, 2020). One contributing factor to the low number of approved drugs is cardiotoxicity. ...
... For example, as noted in Table 1, mean differences between baseline and follow-up between groups, variably reported as the change within or between groups, were reported in ATRU-4 [38], MOMENTUM3 [49], REHAB-VAD [57], CLP [59], PEERLESS-HF [61], and Effects of Levosimendan [66]. Other trials have compared the mean differences in changes in scores (to reflect the degree of improvement or worsening, as has been done in DAPA-HF [43], EMPEROR-REDUCED [39], EXPLORER-HCM [40], VITALITY [41], COAPT [42], DEFINE-HF [44], PARTNER3 [45], ATTR-ACT [46,47], FNTC [48], IRONOUT-HF [54], PAL-HF [50], PARADIGM-HF [51], PARTNER 2 [52], TELE-HF [53], TOPCAT [55], PCDM [56], PREFER [58], MADIT-CRT [60], PARTNER1 [62], SHIFT [63], FAIR-HF [64], HF-ACTION [37], and TTT [65]) ( Table 1). By only reporting means, small average changes are often observed because these means reflect the averages of the patients who improved, were unchanged, and worsened. ...
... There has been remarkable progress in treatment of ATTR amyloidosis. Treatment with tafamidis (an agent that stabilizes the transthyretin molecule) shows improved survival in cardiac ATTR amyloidosis(7). ATTR lends itself to gene targeting due to the apparent lack of critical need for transthyretin in human physiologyfrom silencing RNA to the first study of gene editing agent as a single shot "curative" treatment (8). Daratumumab (a monoclonal antibody directed to CD38) in combination with chemotherapy has become the first licensed treatment for AL(9 ...
... Comparable to these results are the data obtained with non-Val30Met mutations [26][27][28][29]. An additional evaluation of efficacy and safety in ATTR patients reaffirmed the beneficial effects of TAF during long-term treatment and in the early stages of the disease [24,[34][35][36][37][38][39]. Ongoing open-label studies have found that the progression of neurological disease is more severe in patients with higher baseline neuropathy impairment score (NIS) values (more advanced stages of the disease), which justifies the need for early treatment [40]. ...
... Comparable to these results are the data obtained with non-Val30Met mutations [26][27][28][29]. An additional evaluation of efficacy and safety in ATTR patients reaffirmed the beneficial effects of TAF during long-term treatment and in the early stages of the disease [24,[34][35][36][37][38][39]. Ongoing open-label studies have found that the progression of neurological disease is more severe in patients with higher baseline neuropathy impairment score (NIS) values (more advanced stages of the disease), which justifies the need for early treatment [40]. ...
... This was the first therapy to show improved survival of these patients. 40 In many cases of dysautonomia, reports of recent viral infections are identified, especially by herpesviruses, Epstein-Barr and Coxsackie. Autoantibodies to ganglionic acetylcholine receptors (AChr) were found in 50% of patients with PAF, in 7% of patients with POTS and 0% in controls. ...
... This delay reflects the insidious onset of non-specific symptoms and underscores the need for objective biomarkers of onset and regular monitoring of asymptomatic carriers of pathogenic TTR mutations. Early identification of ATTR amyloidosis has become increasingly important with the recent approval of a number of disease-modifying therapies, including transthyretin stabilizers [27], small interfering RNA [28], and antisense oligonucleotides [29]. ...