THAOS: TTR Amyloidosis Patient Registry

www.thaos.net

THAOS Summary for Physicians and Professionals:

The Transthyretin Amyloidosis Outcomes Survey (THAOS) is a longitudinal, observational survey open to all patients with transthyretin amyloidosis (ATTR). The principal aim of the outcome survey is to better understand and characterize the natural history of the disease by studying a large and heterogeneous patient population. Survey data may be used to develop new treatment guidelines and recommendations, and to inform and educate clinicians about the management of this disease.

THAOS Background

The hereditary forms of ATTR are autosomal dominantly inherited diseases with variable penetrance. There are over 80 known amyloidogenic mutations of TTR, which result in variable phenotypic expressions that commonly affect the peripheral nerves, heart, kidney or eyes. The disease is progressive and fatal with an average survival between 9-11 years. The phenotype varies between different mutations but also within the same mutation. The most prevalent neuropathic mutation (ATTR Val30Met) gives rise to a peripheral and autonomic neuropathy with an average age at onset that varies between different endemic areas from 37 to 56 years of age. Cardiomyopathy is also associated with this mutation.

The mutations with predominantly heart manifestations include the Danish ATTR Ile111Met mutation and the ATTR V122I mutation, which is present in approximately 3.5% of African-American population. In addition, wild-type (native) TTR can misfold into amyloid fibrils which are deposited in the myocardial interstitium. This condition, known in the literature as senile systemic amyloidosis, primarily affects elderly (>70) men. Regardless of whether the TTR amyloid fibrils are as a result of a mutation or the aging process, the condition is characterized by a restrictive cardiomyopathy with thickened ventricular walls, diastolic dysfunction, and congestive heart failure.

The only currently available disease modifying treatment for TTR-amyloidosis is liver transplantation.

The clinical course of many mutations is scarcely known, and for the more common mutations the clinical presentation is complex and the impact of different organ manifestations on prognosis has not been determined. Therefore, an international, longitudinal, observational survey open to all patients with TTR-amyloidosis is needed, especially to determine the effect of various treatment regimes.

THAOS Objectives

In collaboration with external experts, FoldRx has developed the Transthyretin Amyloidosis Outcomes Survey (THAOS), an international, longitudinal, observational survey open to all patients with transthyretin amyloidosis. The principal aims of the survey are to better understand and characterize the natural history of TTR amyloidosis by studying a large and heterogeneous patient population.

Specifically, the survey objectives are:

• To describe the population of patients affected with TTR amyloidosis.
• To enhance the understanding of disease natural history, including the variability and progression of the hereditary and acquired forms of the disease
• To better understand the genotype – phenotype relationship in hereditary TTR amyloidosis (ATTR)
• To compare the progression of disease and overall survival in patients with ATTR with and without liver transplant
• To foster an international community of medical experts who will develop recommendations on the clinical management of TTR amyloidosis
• To better understand, manage and treat patients with TTR amyloidosis through publication of the survey data
• To evaluate treatment modalities that may benefit patients with TTR amyloidosis

THAOS Methods

THAOS is a global, multi-center, longitudinal observational survey open to all patients with TTR-associated amyloidosis, including both inherited and wild-type disease. It is open-ended with a minimum duration of 10 years. Patients will be followed as long as they are able to participate.

It is anticipated that THAOS will enroll several thousand patients across 50 or more survey sites over the 10-year enrollment period. Scientific and clinical disease experts will analyze and interpret these data and provide guidance and oversight of the survey to ensure that its goals are met.

The frequency and type of clinical and laboratory assessments will be performed according to the physician’s standard of care. Physicians are not required to modify their standard assessments or treatment interventions for patients. Patients will continue to receive their current medications and all other standard care for their disease.

THAOS allows for data to be recorded at any time during a patient’s participation in the survey. It is recommended that assessments be recorded in the THAOS database at least annually, or more often as needed. Final data recording will occur when the survey is completed, if the patient dies, or if the patient elects to discontinue the survey.

Data will be entered into a secure, confidential interactive internet-based application that allows for remote data entry through locally secured connections. The THAOS database system is designed to be an intuitive tool for each Investigator to enter and review data for patients at any time during the survey.

THAOS Management

THAOS combines the experience and infrastructure a pharmaceutical company brings in establishing and maintaining a complicated international registry and the scientific oversight and independence a Scientific Board brings to insure credible data analysis and publication.

FoldRx will be the legal repository of the THAOS database and is responsible for all operational aspects of the registry. FoldRx will be responsible for site identification, site initiation, site support during patient enrollment, database maintenance and statistical and logistical support to the Scientific Board. The THAOS Scientific Board is comprised of international amyloid experts and will be responsible for the analysis and timely public dissemination of the THAOS data on an on-going basis.

If you are a physician interested in becoming a THAOS investigator, please email THAOS@foldrx.com or call 617-252-5500 and ask to speak with a THAOS project manager. You may also go directly to the THAOS website.