Cambridge, MA, April 21, 2010 – FoldRx Pharmaceuticals, Inc. (FoldRx) today announced that researchers presented results from the successful pivotal trial of tafamidis meglumine (tafamidis) at the XII International Symposium on Amyloidosis in Rome, Italy. Tafamidis, the company’s lead compound, is being investigated as a disease modifying therapy for TTR amyloid polyneuropathy (ATTR-PN), a progressive and life-threatening neurodegenerative disease that affects an estimated 10,000 patients worldwide.
In addition to the clinical results, researchers also presented new findings on studies designed to better understand and clinically assess the natural history of TTR amyloidosis (ATTR) with cardiomyopathy (ATTR-CM) or polyneuropathy (ATTR-PN).
FoldRx announced top-line results from the tafamidis study in July 2009. Full study results, presented in an oral presentation at the XII International Symposium on Amyloidosis, demonstrate that tafamidis treatment significantly halts or slows disease progression in ATTR-PN, reduces the burden of disease after 18 months compared to placebo, and appears to be safe and well tolerated.
“Tafamidis holds the promise of being the first disease-modifying pharmacological therapy for ATTR-PN by altering the neurological deterioration characteristic of this disease,” said Teresa Coelho, M.D., Hospital Santo Antonio in Porto, Portugal, a principal investigator in the study and one of the worldwide experts on the disease.“Tafamidis was well tolerated in trials, and physicians and patients eagerly anticipate this once-daily, oral treatment as an alternative to liver transplantation.”
“The consistency of the results across the various endpoints and analyses provide important evidence for the therapeutic value of tafamidis in the treatment of ATTR patients,” said Richard Labaudinière, Ph.D., President and CEO of FoldRx.“We are very excited and encouraged by the results of the trial and look forward to bringing this innovative therapy to patients worldwide. We anticipate filing marketing applications in the second half of 2010.”
In addition to the interventional study results, data describing the appropriate outcome measures and disease progression in patients with ATTR was also presented.Baseline patient data was described from the Transthyretin Amyloidosis Outcomes Survey (THAOS), a global, ongoing observational patient survey launched by FoldRx in 2008 and designed to characterize disease history, regional differences, and genotypic-phenotypic relationships of ATTR. More than 300 patients from 14 countries have been enrolled in this survey. Information on the registry can be found at www.thaos.net. Results were also presented from longitudinal and cross-sectional natural history studies in ATTR-CM and ATTR-PN that are helping to better understand and evaluate disease progression in these patient populations.
Presentations
Tuesday, April 20 14:30 – 16:25 CEST (8:30 – 10:25 am EDT)
· Oral Presentation #54: Initial findings from the Transthyretin Amyloidosis Outcomes Survey. (THAOS) – A global web-based registry
Tuesday, April 20, 16:30 – 17:30 CEST (10:30 – 11:30 am EDT)
· Poster Presentation # 89: A prospective evaluation of the morbidity and mortality of transthyretin amyloid cardiomyopathy (ATTR-CM): The Transthyretin Amyloidosis Cardiac Study (TRACS)
· Poster Presentation # 98: Relationship between objective measures of neuropathy and quality of life in stages of severity of transthyretin familial amyloid Polyneuropathy
Wednesday, April 21, Plenary Session 8:00 – 9:45 CEST (2:00 – 3:45 am EDT)
· Oral Presentation # 66: Tafamidis (Fx-1006A): a first-in-class disease-modifying therapy for transthyretin familial amyloid polyneuropathy
About tafamidis
Tafamidis is an oral, small molecule, first in class pharmacological chaperone and disease modifying agent for the treatment of ATTR-PN.The drug stabilizes wild-type and variant TTR, prevents misfolding of the protein by preventing tetramer dissociation and inhibits the formation of TTR amyloid fibrils. In the pivotal clinical trial, inhibition of TTR tetramer dissociation was demonstrated in patients receiving tafamidis.This inhibition was correlated with the clinical effects of halting/slowing disease progression as evidenced by the clinical and neurophysiological endpoints. Tafamidis also appeared to be well tolerated over 18 months of treatment. A majority of the patients completing this study are participating in an open label 12 month study evaluating the long term safety and efficacy of tafamidis.
In addition to the pivotal Phase II/III study in V30M ATTR-PN patients, an open-label Phase II study in patients with non-V30M TTR amyloidosis is ongoing. Data are expected in Q2 2010.FoldRx is also conducting a Phase II trial with tafamidis in patients with TTR amyloid cardiomyopathy, with the results anticipated in Q2 2010.
Tafamidis has orphan drug designation in both the U.S. and European Union (EU) and Fast Track designation in the U.S. for the treatment of TTR amyloid polyneuropathy, as well as an orphan drug grant from the FDA.
Tafamidis was developed based on the pioneering work of Dr. Jeffery Kelly, a scientific co-founder of FoldRx, from Scripps Research Institute, La Jolla, CA.
About Transthyretin Amyloidosis
TTR amyloidosis is a slowly progressive, multifaceted disease that primarily affects the peripheral and autonomic nervous systems and the heart.ATTR-PN is a relatively late onset autosomal dominant disease characterized by inexorable neurodegeneration associated with sensory loss, motor weakness and autonomic dysfunction, including dizziness, gastrointestinal disorders, sexual dysfunction and urinary incontinence. Epidemiology studies estimate the patient population at 10,000 worldwide.
The cardiomyopathy associated with this disease is due to infiltration of amyloid in the myocardium interstitium, leading to diastolic dysfunction progressing to restrictive cardiomyopathy and heart failure. The predominant mutation, V122I, is present in approximately four percent of the U.S. African American population.Wild-type (normal) TTR can also form amyloid, particularly in the elderly in whom approximately 15-25% of individuals over 80 have demonstrable cardiac deposition. TTR amyloidosis is ultimately fatal, with liver and/or heart transplantation the only currently available treatments.
TTR, a transport protein for thyroxine and retinol binding protein, is produced primarily in the liver and circulates in the plasma as a tetramer.It is believed that the disease is caused by TTR tetramer dissociation into monomers that misfold resulting in amyloid deposits in various tissues.Inhibition of tetrameric dissociation, the rate limiting step in amyloid formation, should inhibit further amyloid deposition and stop progression of disease.
About the pivotal study
The international, randomized, double-blind, placebo controlled pivotal study enrolled 128 patients in eight sites suffering from TTR amyloid polyneuropathy, with confirmed V30M TTR mutation, the most prevalent disease variant.Participants underwent an 18-month treatment regimen with once a day dosing of tafamidis or placebo. The co-primary endpoints measured response to treatment at 18 months via the Neuropathy Impairment Score - Lower Limb (NIS-LL), and quality of life, as measured by the Norfolk QOL-DN.These two endpoints correlate with disease severity and are sensitive and relevant endpoints in demonstrating neuropathy disease progression.
About FoldRx Pharmaceuticals, Inc.
FoldRx Pharmaceuticals is a development and discovery company focusing on first-in-class, disease-modifying, small molecule therapeutics to treat diseases of protein misfolding and aggregation (amyloidosis). Protein misfolding is increasingly being recognized as an underlying cause of many chronic degenerative diseases. By applying FoldRx’s proprietary expertise in protein folding and its platform for drug and target discovery, the company is building a pipeline, initially for neurodegenerative and cardiovascular conditions. FoldRx’s pipeline includes a program in advanced clinical development to treat genetic neurologic and cardiovascular disorders, Transthyretin (TTR) Amyloid Polyneuropathy (ATTR-PN) and TTR Amyloid Cardiomyopathy (ATTR-CM), and a discovery program in Parkinson’s disease and cystic fibrosis, based on its broad, proprietary, yeast-based drug discovery platform. For more information on FoldRx, please visit the company’s web site at www.foldrx.com.
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