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Amyloidosis Research Consortium Calls For Regulators To Adopt New Surrogate End Point For Pivotal Clinical Trials In Patients with AL Amyloidosis

  • Cardiac functional biomarker is a validated end point used universally by amyloidosis specialists to determine treatment outcomes and to predict survival
  •  Establishment of a surrogate end point would bring new therapies to patients sooner, preventing death and encouraging the development of new targeted therapies

BOSTON, Mass. – October 5, 2015 – A new white paper from the Amyloidosis Research Consortium concludes that NT-proBNP, a functional biomarker predictive of survival, is a clinically and analytically validated functional biomarker that should be accepted as a surrogate end point in pivotal clinical trials to accelerate the development of therapeutics for AL amyloidosis. This white paper is part of a multifaceted strategy to accelerate the drug development pathway for patients with amyloidosis, which will be highlighted by a public meeting that will include patients, expert physicians from around the world, and regulators at the US Food and Drug Administration (FDA) on November 16, 2015, in Silver Spring, Maryland.

AL amyloidosis is an ultra-rare, progressive 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.

“Patients with AL amyloidosis  have significant morbidity and mortality and desperately need new therapeutic options,” said Isabelle Lousada, president and CEO of the Amyloidosis Research Consortium. “We believe strongly that the use of NT-proBNP as a surrogate end point will encourage development of targeted therapeutics to improve patient care and survival in patients suffering from this rare and fatal disease.”

NT-proBNP has emerged as the gold standard functional biomarker for the determination of treatment outcome for patients with AL amyloidosis. A standard laboratory test measures levels of NT-proBNP with 100% sensitivity from a small blood sample.

“NT-proBNP response or progression predicts improvement or progression of cardiac dysfunction, treatment efficacy, and survival,” said Raymond L. Comenzo, MD, Attending Physician at Tufts Medical Center and Professor of Medicine and Pathology at Tufts University School of Medicine. “Importantly, as demonstrated through nine separate global clinical studies, NT-proBNP is a validated and practical biomarker that can be implemented as a primary end point in response to therapy in clinical trials of patients with AL amyloidosis independent of type of therapy or regimen.”

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. This white paper urges the FDA to adopt the use of NT-proBNP as a surrogate end point for survival in clinical trials of AL amyloidosis. 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.

“Overall survival as an end point requires a larger study population and a longer assessment period, in which the use of NT-proBNP as a surrogate end point, with survival as a follow-up, may require less than half the time,” commented Giampaolo Merlini, MD, of the Amyloidosis Research and Treatment Center at the University of Pavia and IRCCS Policlinico San Mateo in Italy. “The use of NT-proBNP as a surrogate end point is particularly important to minimize treatment-related toxicity and mortality and to conduct systematic clinical research more rapidly to save patient lives.”

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 approximately 1200 patients. Overall, seven large independent studies conducted in almost 2000 patients have consistently demonstrated that NT-proBNP response after treatment improves cardiac function and prolongs survival in patients with AL amyloidosis.

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

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