FoldRx Pharmaceuticals Inc.

Cambridge, MA, United States

FoldRx Pharmaceuticals Inc.

Cambridge, MA, United States

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Plante-Bordeneuve V.,CHU Henri Mondor | Suhr O.B.,Umeå University | Maurer M.S.,Columbia University | White B.,FoldRx Pharmaceuticals Inc. | And 2 more authors.
Current Medical Research and Opinion | Year: 2013

Background: Transthyretin (TTR) amyloidosis-the most common type of hereditary amyloidosis-Also has an acquired form and is observed in geographically dispersed populations. TTR amyloidosis is marked by considerable clinical heterogeneity, and the main phenotypes are neurologic and cardiovascular. Methods: THAOS is an international, noninterventional, longitudinal, observational registry designed to evaluate overall survival in patients, better understand genotype-phenotype relationships and the natural history of TTR amyloidosis, and evaluate the effects of liver transplantation and other treatments on disease progression in TTR amyloidosis. All individuals with a confirmed TTR mutation with or without a diagnosis of TTR amyloidosis and patients with wild-type TTR amyloidosis are eligible to be enrolled in the registry. Purpose: To describe the design and methodology of the recently established registry. Procedures for data collection are outlined and a minimum set of assessments for the standard evaluation of all subjects with TTR amyloidosis is described. Demographic information, TTR genotype, medical history, family history of the disease, and transplant history are assessed at baseline. On return visits, signs and symptoms of the disease are evaluated, general examinations are conducted, and laboratory data, measures of neurologic and cardiovascular function, and quality of life are assessed according to the standard of care for patients. Visits on at least a biannual basis are recommended. The registry will remain open for a period of at least 10 years. Results: The initial experience suggests that the registry is characterized by a comprehensive set of data elements which can be completed by providers from the various clinical backgrounds who administer care to individuals with TTR amyloidosis. Conclusion: As of September 2011, 30 centers in 15 of the 19 countries participating in the THAOS registry have enrolled 975 patients. Such data provide a representative sample of the global TTR amyloidosis patient population, including asymptomatic TTR variant carriers, which can inform the natural history of the disease and offer the potential to evaluate novel therapeutic modalities in diverse patient subpopulations. © 2012 Informa UK Ltd All rights reserved.


Bhuiyan T.,Columbia University | Helmke S.,Columbia University | Patel A.R.,Tufts Medical Center | Ruberg F.L.,Boston University | And 4 more authors.
Circulation: Heart Failure | Year: 2011

Background-ATTR cardiac amyloidosis can result from a mutated variant of transthyretin (eg, V122I) or wild-type variant (ATTRwt). We evaluated pressure-volume (PV) indices at baseline and over time to further characterize abnormal pump function in these subjects. Methods and Results-Twenty-nine subjects (18 with ATTRwt and 11 with ATTRm (V122I) had 2-dimensional echocardiograms with complete Doppler measures at baseline and every 6 months for up to 2 years. PV indices were derived from echocardiographic measures of ventricular volume coupled with sphygmomanometer-measured pressure and Doppler estimates of filling pressure. The end-systolic and end-diastolic PV relations and the area between them as a function of end-diastolic pressure, the isovolumic PV area (PVAiso), were calculated. Clinical, demographic, and PV indices were compared between V122I and ATTRwt subjects and between survivors and nonsurvivors at baseline and over time. Cox proportional hazards model identified correlates for mortality. Stroke volume decline was associated with alterations in ventricular-vascular coupling and a decrease in ventricular capacitance with significant decrement in ejection fraction (56±12% to 48±14%, P=0.0001) over 18 months. PVAiso was lower in V122I subjects compared with wild-type at baseline and declined over time. Twelve (41%) subjects died or underwent a cardiac transplant after a mean follow-up of 478 days (range, 31 to 807). Multivariable survival analysis demonstrated that initial ejection fraction (a measure of ventricular-vascular coupling) <50% was associated with increased mortality (hazard ratio, 6.6; 95% confidence interval, 1.1 to 40.3). Conclusions-In ATTR cardiac amyloidosis secondary to a V122I mutation and wild-type transthyretin, PV analysis reveals alterations that are associated with reductions in the ability of the ventricle to perform work and, ultimately, with reduced survival in these subjects. © 2011 American Heart Association, Inc.


Merlini G.,University of Pavia | Plante-Bordeneuve V.,CHU Henri Mondor | Judge D.P.,Johns Hopkins University | Schmidt H.,Universitatsklinikum Munster | And 5 more authors.
Journal of Cardiovascular Translational Research | Year: 2013

This phase II, open-label, single-treatment arm study evaluated the pharmacodynamics, efficacy, and safety of tafamidis in patients with non-Val30Met transthyretin (TTR) amyloidosis. Twenty-one patients with eight different non-Val30Met mutations received 20 mg QD of tafamidis meglumine for 12 months. The primary outcome, TTR stabilization at Week 6, was achieved in 18 (94.7 %) of 19 patients with evaluable data. TTR was stabilized in 100 % of patients with non-missing data at Months 6 (n = 18) and 12 (n = 17). Exploratory efficacy measures demonstrated some worsening of neurological function. However, health-related quality of life, cardiac biomarker N-terminal pro-hormone brain natriuretic peptide, echocardiographic parameters, and modified body mass index did not demonstrate clinically relevant worsening during the 12 months of treatment. Tafamidis was well tolerated. In conclusion, our findings suggest that tafamidis 20 mg QD effectively stabilized TTR associated with several non-Val30Met variants. © 2013 The Author(s).


Trademark
FoldRx Pharmaceuticals Inc. | Date: 2012-02-28

Orally administered pharmaceutical preparations available by prescription only, for the treatment of a rare protein misfolding disease, namely, amyloidosis.


Trademark
FoldRx Pharmaceuticals Inc. | Date: 2010-07-26

Orally administered pharmaceutical preparations available by prescription only, for the treatment of a rare protein misfolding disease, namely, amyloidosis.


Trademark
FoldRx Pharmaceuticals Inc. | Date: 2010-07-26

Orally administered pharmaceutical preparations available by prescription only, for the treatment of a rare protein misfolding disease, namely, amyloidosis.


Trademark
FoldRx Pharmaceuticals Inc. | Date: 2010-03-20

Orally administered pharmaceutical preparations available by prescription only, for the treatment of a rare protein misfolding disease, namely, amyloidosis.


Trademark
FoldRx Pharmaceuticals Inc. | Date: 2010-03-20

Orally administered pharmaceutical preparations available by prescription only, for the treatment of a rare protein misfolding disease, namely, amyloidosis.


Compounds (I), compositions and methods are provided for stabilizing transthyretin and for treating, preventing, or ameliorating one or more symptoms of transthyretin mediated diseases.formula I:Y is COOH, COOR^(5), CONR^(7)R^(8), tetrazolyl, CONHOH, B(OH)_(2), CONHSO_(2)Ar, CONHCH(R^(6))COOH, OH, CH_(2)OH or -(CH_(2))_(n)-C(R^(6))(NH_(2))-COOH;X is O;Het is heteroaryl, optionally substituted with halo, OR, alkyl or haloalkyl;Ar, R, R^(5) - R^(8) and n are as described herein.


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