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Amyloidosis Research Consortium Announces Publication of Seminal Manuscript in Peer-Reviewed Journal Leukemia Encouraging Use of NT-proBNP as Endpoint in Clinical Trials.

  • International AL amyloidosis expert community agrees N-terminal pro-brain natriuretic peptide (NT-proBNP) is analytically validated and clinically qualified to be used as a surrogate endpoint for survival in clinical trials of patients with AL amyloidosis
  • Use of NT-proBNP as surrogate endpoint will greatly facilitate the development of targeted therapies for AL amyloidosis
  •  ARC actively working to validate NT-proBNP through U.S. Food and Drug Administration biomarker qualification program

BOSTON, Mass. – July 20, 2016 – The Amyloidosis Research Consortium today announced the publication of a landmark paper concluding that NT-proBNP response, a clinically- and analytically-validated functional biomarker predictive of survival for patients with AL amyloidosis, should be accepted as a surrogate end point for survival in pivotal clinical trials to greatly facilitate the development of targeted therapeutics. The pivotal paper was published by leading experts in the field in the peer-reviewed journal Leukemia and can be accessed here.

AL amyloidosis is an ultra-rare, progressive and fatal disease characterized by the accumulation of abnormal, misfolded protein (amyloid) in various tissues and organs. This amyloid protein builds up in the heart, kidneys, liver, soft tissue, and nervous system, resulting in multiorgan failure and death. As many as 70% of patients with AL amyloidosis have accumulations of amyloid in their hearts that will lead to cardiomyopathy and ultimately to death. No therapies have been approved for the treatment of patients with AL amyloidosis, or any form of systemic amyloidosis, in the United States.

“NT-proBNP has emerged as an analytically validated, gold standard biomarker for the determination of cardiovascular risk and disease in patients with AL amyloidosis,” said Giampaolo Merlini, MD, of the Amyloidosis Research and Treatment Center at the University of Pavia and IRCCS Policlinico San Mateo in Italy, and senior author of the study. “In five independent studies in almost 1500 patients, NT-proBNP responses consistently reflect changes in cardiac function and predict survival in patients with AL amyloidosis after interventional treatment. Importantly, NT-proBNP predicts clinical outcome and survival independent of therapy type, treatment class or regimen.”

“A significant barrier to therapeutic development is posed by all diseases that are serious but rare, as traditional clinical trials with clinical endpoints such as survival and progression free survival are difficult, if not impossible to conduct,” said Raymond L. Comenzo, MD, a study author and Founding Director of the John Conant Davis Myeloma and Amyloid Program and Director of the Blood Bank and Stem Cell Processing Laboratory at Tufts Medical Center. “The amyloidosis expert community is in agreement that NT-proBNP should be used as a surrogate end point for survival in patients with AL amyloidosis with cardiac involvement.”

Overall survival as an endpoint requires a larger study population and a longer assessment period, where the use of NT-proBNP as a surrogate endpoint may require less than half the time. In 2012, the International Society of Amyloidosis (ISA) established and validated NT-proBNP response as an indicator of organ response and as a surrogate marker of survival in AL amyloidosis.

In November 2015, the Amyloidosis Research Consortium held a public meeting including patients, expert physicians from around the world, and regulators at the US Food and Drug Administration (FDA). More than 240 people attended, with patients voicing the huge unmet need for new medical treatment options, the urgency to cut down lengthy development timelines and the desire to make these therapies available to patients with AL amyloidosis in a timely manner. This publication adds to a multifaceted strategy to accelerate the drug development pathway for patients with amyloidosis.

The 2012 FDA Safety and Innovation Act (FDASIA) created new opportunities to use surrogate end points to bring new therapies to patients with rare diseases in an expedited manner. The consensus among AL amyloidosis experts is that NT-proBNP is the only clinically validated surrogate end point for survival after treatment. Lowering NT-proBNP and achieving NT-proBNP response is the ultimate treatment objective that should be accepted as a surrogate for survival in AL amyloidosis clinical trials for patients with cardiac involvement.

Isabelle Lousada, founder and CEO of the Amyloidosis Research Consortium and an amyloidosis patient commented, “We believe that using NT-proBNP as a surrogate endpoint for survival represents a concrete, positive movement toward the rapid assessment of new therapeutics for AL amyloidosis and we are working with the FDA to validate NT-proBNP through the biomarker qualification program, to potentially save many lives.”

About the Amyloidosis Research Consortium

The Amyloidosis Research Consortium was established to address critical needs in clinical trials and related research for the underserved group of systemic amyloid diseases. It brings together experts in the field to address the challenges that exist in developing diagnostic tools and carrying out collaborative and innovative clinical trials. The Amyloidosis Research Consortium is committed to building collaborative relationships between patients, academia, industry, foundations, federal funders, and regulators to facilitate and speed new therapies to market. The Amyloidosis Research Consortium is focused on increasing the amount of research in amyloidosis and building a prioritized portfolio of translational research and clinical research. Its aim is to address the urgent, unmet medical needs in patients with amyloidosis. For more information, visit www.arci.org.

Recently, ARC launched The Amyloidosis Clinical Resources App to serve as a mobile resource for healthcare professionals faced with the complex clinical presentations of this rare and difficult to diagnose disease. It includes definitions, etiology, pathogenesis, and clinical suspicion and diagnosis of AL, ATTR types, and AA amyloidosis as well as a collection of interactive tools, novel agents, clinical trials and additional resources. It is available for FREE and can be downloaded to a tablet or smartphone from iTunes and GooglePlay.

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