Highlights from ASH 2017: Research Update

AL amyloidosis takes center stage as ARC board member Dr. Giampaolo Merlini gives the Ham-Wasserman Lecture.

AL amyloidosis was placed in the spotlight at the American Society of Hematology (ASH) annual meeting in Atlanta, Georgia when ARC Board member Dr. Giampaolo Merlini, from the University of Pavia, Italy, gave the prestigious keynote Ham-Wasserman lecture on the first day.

Speaking to an audience of several thousand hematologists, Dr. Merlini provided an overview of the recent advances in several key areas in AL amyloidosis. These included; a better understanding of the molecular mechanisms that give rise to AL amyloidosis; the importance of early diagnosis; the need to tailor treatment to individuals; and the role of cardiac biomarkers at critical stages of the disease particularly at diagnosis, when risk stratifying patients and measuring response to treatment.

Dr. Merlini also discussed the exciting developments in the drug pipeline. He explained how different approaches were being used to target not only the cause of AL amyloidosis but also its consequences, noting how new drugs aimed at accelerating the breakdown and removal of amyloid deposits were showing promising results in clinical trials.

Isablelle Lousada, CEO of the Amyloidosis Research Consortium, said, “We’re very proud that Dr. Merlini was recognized by his peers for his work in amyloidosis and are extremely grateful that he was given such a platform to raise awareness among fellow clinicians."

AL amyloidosis was featured in other scientific sessions where the latest data from a number of clinical trials were shared. In one session, results from two separate Phase II trials of daratumumab for relapsed AL amyloidosis patients were presented back to back. Daratumumab is a monoclonal antibody which targets and destroys the abnormal plasma cells that are responsible for producing the amyloid light chains.

Dr. Vaishali Sanchorawala, from the Boston Medical Center, presented the results from the first trial noting that patients achieved rapid reduction in free light chain levels after the first dose of daratumumab and further reductions with subsequent doses. Patients also showed improved kidney and heart function with continued treatment up to six months. Side-effects associated with daratumumab were mild and easily managed.

Results from the second trial presented by Dr. Murielle Roussel, from the University Cancer Institute of Toulouse, Oncopole, also demonstrated that patients achieved rapid responses with daratumumab. Further analysis showed that those who responded well after the first dose were more likely to achieve a complete or near complete response and have better outcomes.

In other talks, data from a Phase I trial of the novel drug CAEL-101 also showed promise. CAEL-101 is one of a new generation of drugs which works by breaking down the amyloid deposits. When given to AL amyloidosis patients who had already received plasma cell-directed treatment but had persistent organ dysfunction, rapid, early and sustained improvements in organ function were observed. Plans are underway to further investigate CAEL-101 in more patients.

Kristen Hsu, Director of Clinical Research at the Amyloidosis Research Consortium, said, “Step changes are being made in the treatment landscape for AL amyloidosis. The results we have seen here at ASH this year highlight the fact that we are very close to having specific treatments for AL amyloidosis."

Read part one of ARC's ASH recap here.
 

ARC at ASH: Part 1

The Amyloidosis Research Constortium attends the American Society of Hematology meeting in Atlanta

 

(L to R): Isabelle Lousada, Dr. Robert Kyle and Eric Low at ARC's booth at the ASH meeting.

(L to R): Isabelle Lousada, Dr. Robert Kyle and Eric Low at ARC's booth at the ASH meeting.

Every December thousands of physicians, researchers and healthcare professionals gather for the biggest hematology event of the year: the American Society of Hematology (ASH) meeting. ASH is the world’s largest professional society serving clinicians and scientists around the world working in blood diseases. While at the conference, ARC's objectives were to (1) promote amyloidosis awareness and the work of ARC, (2) learn about the latest advances in AL amyloidosis treatment and (3) to collaborate with key stakeholders in the field.

Interest in amyloidosis has significantly grown over the past few years. For the first time, ASH championed amyloidosis, inviting Dr. Giampaolo Merlini, co-chair of ARC's Board, to give the Ham-Wasserman Plenary lecture on AL amyloidosis to a large number of the 26,000 delegates—a hugely significant and exciting moment for everyone in the amyloidosis community. Over the course of the three-day exhibition there was great engagement with doctors, nurses and researchers at the ARC booth. ARC shared updates on our current programs, highlighted our educational and awareness resources, and discussed work going on in amyloidosis research across the world. There was also considerable interest in the latest results from clinical trials of monoclonal antibody therapy in amyloidosis, which you can read about in our scientific round up here.

Dr. Giampaolo Merlini's lecture on AL amyloidosis at ASH meeting.

Dr. Giampaolo Merlini's lecture on AL amyloidosis at ASH meeting.

As well as exhibiting at ASH, the ARC team arrived in Atlanta a day early to hold a series of meetings with key opinion leaders in amyloidosis. Such meetings are the cornerstone of ARC's collaborative model and crucial in developing the infrastructure needed to accelerate progress in amyloidosis treatment and help patients access and benefit from future treatments as quickly as possible.

The team returned from Atlanta and the excitement of the ASH meeting with new connections made, renewed enthusiasm and invigorated for the growth of ARC programs in 2018! 

You can find more information and pictures from the ASH meeting on ARC’s Twitter @Amyloidosis_ARC and with hashtag #ASH2017.

The Amyloidosis Research Consortium Launches V.2 of Clinical Trial Tool

My Amyloidosis Pathfinder (MAP) is Changing the Way Patients Navigate Their Diagnosis

My amyloidosis pathfinder

The Amyloidosis Research Consortium (ARC) is excited to launch the latest version of the My Amyloidosis Pathfinder (MAP) tool. This groundbreaking tool was created to help connect amyloidosis patients to appropriate treatment centers and clinical trials for their disease. The latest updates will help ARC more effectively manage user data, keep the data secure and share it anonymously with researchers to help drive amyloidosis research forward.

Since the inaugural launch of MAP in March of this year, more than 300 patients and caregivers have signed up for the tool. MAP has successfully matched patients to newly opened clinical trials. Finding the right treatment center is a critical step in getting treatment. MAP also identifies amyloidosis treatment centers with the capability to provide excellent care for their specific type of amyloidosis. ARC provides extensive information on each center, allowing patients to make informed decisions that are right for them.

79% of patients said with better information and access they would consider participating in a clinical trial -- ARC Patient Journey Study, 2015

In addition to matching patients to treatment centers, MAP also matches patients to clinical trials for which they may be eligible. Clinical trials are a critical step in the development of much needed drugs for amyloidosis patients, however, these important trials are often significantly delayed due to lack of participants. This can significantly slow down the rate at which new drugs are discovered, tested and made available to patients. In amyloidosis, clinical trials can be a great way to access promising new treatments.

"The inability to complete trials in a timely manner delays the approval of potentially effective treatments, it represents a huge barrier to the development of much needed treatments for rare diseases such as amyloidosis where no there are no FDA approved therapies." -- Isabelle Lousada, CEO, Amyloidosis Research Consortium

 By providing easy access and trusted support, MAP educates patients about the value of participation. MAP increases enrollment and reduces time for accrual to clinical trials, thereby accelerating the amyloidosis drug development process. Data collected through the online tool also provides valuable information and allows ARC to identify underserved cohorts of patients. This in turn will help inform the design of clinical trials and ensure that research can be conducted efficiently, quickly, and responsibly. MAP is a novel tool in amyloidosis research and ARC is committed to enhancing its capabilites it to help patients find and access the best treatments.

To learn more about MAP, please visit the website: www.myamyloidosispathfinder.org

 

               

Save the Orphan Drug Tax Credit!

We need your help! Contact your senators and representatives today!

Earlier this month, House Republicans proposed eliminating the orphan drug tax credit, which was originally passed as part of the Orphan Drug Act in 1983 as an incentive for drug makers to spur the creation of medicines for rare diseases. Now, the House's proposal eliminates the credit completely and the Senate’s version proposes to cut the credit’s value from 50 percent of qualified clinical testing expenses to 27.5 percent.

With nearly 30 million Americans suffering from rare diseases, we need to do better than the current 4 percent of rare diseases that have an approved treatment. Rare disease drug development is already a monumental task and without this life-saving credit, there is little incentive for drug developers to invest in new drugs for these rare diseases.

Here at ARC, we rely heavily on this credit to be able to work alongside drug companies in developing novel treatments for amyloidosis and, in turn, be able to continue making a significant and material contribution to the curability of systemic amyloidosis diseases.  

"Rare disease drug development is extremely challenging - reducing the orphan drug tax credit is a backward step." --  Isabelle Lousada, CEO, Amyloidosis Research Consortium

We applaud the National Organization for Rare Disorders (NORD) for their advocacy efforts and urge you to visit their website to see the ways  you can take action. Please join us and the hundreds of other organizations in this fight to keep the Orphan Drug Tax Credit in its entirety. 

 

See the Drug Tax Credit coalition letter NORD sent to the Tax Reform Conference Committee here.

Contribute to a Cure. Join our Campaign #10x10x10

 
 
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Each day we are adding another critical reason for you
to ask 10 friends to donate 10 dollars
to the Amyloidosis Research Consortium


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Day 10: Your Partnership

The ARC is heavily reliant on donations and the fundraising efforts of the amyloidosis community, without which, it could not do the important work it does.


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Day 9: Committed Team

The ARC’s highly driven, experienced team works tirelessly every day to advance our efforts on behalf of all patients and their families.


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Day 8: Benefitting Patients

The ARC is focused on making sure that the patients get access to the best possible treatment and care no matter where they live in the world.


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Day 7: Driving Change

The ARC ensures that patients come first by educating and lobbying all those involved in the research, regulation and approval of new treatments.


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Day 6: Patient Centric

The ARC is instrumentally involved in the conception, design and management of the clinical trials in our collaborative network to ensure that they are relevant and address unmet clinical need. 


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Day 5: Strategic Investment

The ARC strategically invests its funds towards research projects most likely to make a material and significant contribution to improving patient outcomes.


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Day 4: Connecting Patients

The ARC is actively connecting amyloidosis patients to clinical trials, giving them access to potential new treatments.


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Day 3: Pioneering Advocacy


The ARC is an exemplar model for patient-led research foundations. The work we do and the progress we make with the FDA and other regulatory bodies is helping to pave the way for other diseases beyond amyloidosis.


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Day 2: Global Research

The ARC is the only patient-driven organization in the world exclusively focused on amyloidosis research.


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Day 1: Improving Diagnosis

The ARC’s awareness and education programs are improving the rate of diagnosis.  
Delayed diagnosis in amyloidosis can be fatal.


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Gene silencing holds promise for treating hereditary ATTR amyloidosis

“Latest clinical trial data strengthen the case for new gene silencing drugs, patisiran and inotersen, to become the first FDA approved treatments for hereditary ATTR amyloidosis patients”

A novel therapeutic approach which exploits the normal biological process of gene silencing, or RNA interference (RNAi), is continuing to show promise as a potential treatment for hereditary ATTR (hATTR) amyloidosis. Results presented recently at the 1st European ATTR Amyloidosis Meeting for Patients and Doctors held in Paris, France, have further demonstrated the benefits of two such RNAi drugs, patisiran and inotersen, for patients with this type of amyloidosis.

Both drugs work by “silencing” the expression of the mutant TTR gene and therefore stop the production of the misfolded transthyretin protein, the cause of the amyloid deposits in hATTR amyloidosis.

Data from the Phase 3 APOLLO trial for hATTR amyloidosis patients with polyneuropathy were presented after an 18-month follow up. Compared to those in the control group, patients receiving intravenous patisiran had significantly lower circulating transthyretin levels, reduced neurological impairment and fewer cardiac symptoms. In addition, patients reported they were more able to carry out activities of daily living, had better overall health and greatly improved quality of life.

Results from the Phase 3 Neuro-TTR also showed that patients benefited significantly from once weekly subcutaneous injections of inotersen in terms of quality of life and measures of neurological function compared to patients in the control group. These were achieved regardless of disease stage, the presence of cardiomyopathy and type of mutation.

“There is such a huge unmet need in amyloidosis treatment, but these results could pave the way for patisiran and inotersen to become the first approved treatments for hATTR amyloidosis patients” said Isabelle Lousada, CEO of the Amyloidosis Research Consortium.

Inotersen has recently been submitted for regulatory assessment in the United States and Europe while patisiran will follow suit in the coming months.

Isabelle Lousada added “These are exciting times for the amyloidosis community. If successful, inotersen and patisiran will not only be the first for amyloidosis but also the first RNAi-based therapeutic drugs to be approved for use in any disease.”

 

 

Physician Spotlight: Dr.Mazen Hanna

"Our patients are what drives us, we want to offer them a better life."

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Dr. Mazen Hanna is a cardiologist and current Co-Director of the Amyloidosis Program at the Cleveland Clinic alongside hematologist, Dr. Jason Valent. He has been a member of the heart failure and cardiac transplant unit in the department of cardiovascular medicine since 2006 as well as the Director of the Heart Failure Intensive Care Unit since 2008.

 

For the past 10 years, Dr. Hanna has taken a special interest in the field of amyloidosis. He first became interested in amyloidosis during his cardiology fellowship where his team diagnosed an elderly woman with AL amyloidosis. From here, his interest grew as he started recognizing more and more cases during his first two years as a staff member at the Cleveland Clinic. After connecting with Dr. Merrill Benson about a particular patient, Dr. Hanna was introduced to and subsequently invited amyloid specialist, Dr. Rodney Falk, to speak about cardiac amyloidosis at the Cleveland Clinic as a visiting professor. Dr. Falk went on to became Dr. Hanna’s mentor over the following years, helping him develop his interest and expertise in the field of amyloidosis.

 

Now Dr. Hanna has built strong clinical and research practices in amyloidosis at the Cleveland Clinic. His clinic treats both AL and ATTR amyloidosis and collaborates with specialists from other fields to provide thoughtful and comprehensive care. On his colleagues, Dr. Hanna boasts, “They take fantastic care of their patients and have an excellent collaboration with our transplant teams. They have an experienced bone marrow transplant team, and in 2014 performed their first heart transplant followed by stem cell transplant for a patient with AL who is now doing very well. The clinic also has experience in liver and heart transplants for hereditary ATTR patients and offers many clinical trials in both AL and ATTR, including trials of NEOD001 and tafamidis".

 

In 2015, one of Dr. Hanna’s patients made a 2 million dollar donation dedicated to research of amyloid heart disease. These funds have allowed him to hire a research staff and pursue investigator-initiated studies. Currently, he is leading a study looking at the incidence of amyloid in tissue samples taken from elderly patients undergoing carpal tunnel surgery. Dr. Hanna is dedicated to collaborative research, working with physicians across the globe, and is focused on the future of amyloidosis, stating, “I am hopeful that we will continue to make progress to fight amyloid heart disease. It is an honor to work with such a collaborative community of scientists and physicians of different specialties who come together to further knowledge and develop treatments. Our patients are what drives us, we want to offer them a better life.”

 

Northern California Support Group Meeting and Patient’s Day Hosted by Prothena

“ Everything we do starts and ends with patients, so spending time with patients who are dealing with devastating diseases like AL or ATTR amyloidosis is central to our ability to keep these perspectives in mind. 

At Prothena, we focus on how our science can be translated into medicines for important diseases. We also love talking about our science, so hosting the ARC at Prothena for a support group meeting provided an incredibly rich learning opportunity and dialogue that we look forward to continuing.”  Sarah Noonberg, MD, PhD, Chief Medical Officer

The Northern California Amyloidosis Support Group which meets quarterly every year, held their 14th annual anniversary meeting in July in South San Francisco.  The event was hosted by the team at Prothena and was a very successful Patient’s Day event with 67 patients and caregivers in attendance. Patients traveled from as far away as Southern California and the Sierra Foothills to participate.  Our agenda included presentations from three Prothena scientists whose slide shows reinforced our growing knowledge of amyloidosis and delighted us with actual microscopic images of macrophages “consuming” the mis-folded light chains.

Patients are our motivation and addressing unmet medical needs guides the work of our scientists.  We don’t have too many opportunities to meet the people who might one day benefit from the medicines we are working on in our labs, but when we do, we always learn something incredibly valuable and leave with renewed inspiration. Working with ARC always provides a great way for us to keep the patient voice in focus.” Wagner Zago, PhD, Chief Scientific Officer

Another highlight of our meeting included tours of the research labs at the beautiful new Prothena facility where group members could see the science in action, up close and personal, and where even the most challenging questions from patients and caregivers were thoughtfully addressed.

 “Working in biotech is incredibly rewarding because there is always the potential to see your efforts translated into a product that enhances length or quality of life for patients. Getting the science right is the first step, but engaging with patients and patient advocacy groups is an incredibly important part of our work because it helps us to understand what people with devastating diseases are dealing with and what is important to them.” Enchi Liu, PhD, Program Team Leader

Rounding out our very busy event were two key amyloidosis physicians from the University of California San Francisco Medical Center – cardiologist Van Selby and hematologist Sandy Wong with 90 minutes of patient Q&A.  Always generous with their time Drs. Selby and Wong are working together at UCSF to build the multi-disciplinary amyloidosis team there and to implement amyloidosis clinical trials. 

For more information on the Northern California Support Group contact Dena Heath: dheath@arci.org

Cardiac AL Amyloidosis Patients Experience Delays in Diagnosis

Data from Recent ARC Study on Patient Journey to Diagnosis 

A survey of patients with all forms of cardiac amyloidosis and their caregivers was conducted in order to understand delays, errors, and inconsistencies in the diagnostic pathway for patients with cardiac amyloidosis and validated using caregiver responses. Data from AL amyloidosis patients was presented at the European Hematology Association (EHA) Madrid Conference in June.

The online survey was developed by the ARC and distributed to the patient mailing lists of ARC, the Amyloidosis Foundation, and Amyloidosis Support Groups in January 2017. Data collected from both patients and their caregivers, documents the initial symptoms and their journey to diagnosis of over 313 AL amyloidosis patients.

This represents the first survey compiling both caregiver and patient experiences with AL amyloidosis. Patients with AL cardiac amyloidosis frequently receive misdiagnoses and sometimes receive incorrect treatment for the misdiagnosed condition. Disease awareness among all specialists is vital, especially among those to whom patients are initially referred due to the nature of their initial symptoms. The data highlights the vital importance of education and awareness in the community to prevent the significant delays patients often experience in gaining the correct diagnosis.

 
click on image to enlarge poster

click on image to enlarge poster

 

The New FDA Commissioner

Dr. Scott Gottlieb has been appointed the commissioner of the Food and Drug Administration (FDA). He is a physician and a cancer survivor, having been successfully treated for Hodgkin’s lymphoma.

Gottlieb has previously commented that the agency's current focus on statistics rather than good medicine is making it too difficult for drugs, especially orphan drugs, to get approved.

The National Coalition for Cancer Survivorship, for which Gottlieb served as a policy advisor, strongly endorsed his nomination to head the FDA, saying he “understands the human toll cancer takes on individuals and families, during both treatment and long-term survivorship. He is open to a wide range of perspectives, including those of the patients whose lives depend on a strong FDA.”

In a statement, Tom Price, the secretary of Health and Human Services, said Dr. Gottlieb’s “background will be crucial” for maintaining the FDA’s high standards for safe treatments “while advancing new, innovative solutions” to the nation’s public health challenges.

In rare diseases, the evaluation of new treatments is often challenging.  We are hopeful that Dr. Gottlieb will champion the need for the FDA to be efficient and patient-focused in the evaluation of vital new therapies for rare diseases like amyloidosis.

 

Coming Together to Make a Difference

ARC Industry Advisory Council Charts a Course for Collaboration

The ARC held its biannual Industry Advisory Council meeting in Boston on March 27th, 2017. The day-long meeting was attended by representatives from pharmaceutical and biotech companies developing new treatments for amyloidosis.  This provides a unique opportunity for these companies to unite and develop partnerships of mutual interest.

Part of the modus operandi of the Amyloidosis Research Consortium is to foster cross-company conversations in order to identify areas of resource-wasting replication.  Precompetitive research, educational awareness programs, and developing a streamlined strategy are primary focal points.

Joining us were the following companies that all have drugs in clinical trials for amyloidosis.

  • Alnylam
  • GSK
  • Ionis
  • Janssen
  • Pfizer
  • Prothena
  • Takeda

We were delighted to welcome two new companies to the council for the first time that have products in early stage development.

  • Caelum
  • Intellia

At the meeting the following areas were prioritized:

  • Market access  
  • Epidemiology
  • Awareness
  • Early detection/diagnosis
  • Clinical endpoints and QOL/PROs

 Participating companies will be partnering with the ARC to develop strategies and launch work streams to address them. We look forward to sharing more details on these key areas in the near future.

 

Rare Disease Week Needs You

Participate as an Amyloidosis Advocate

Rare disease day is on 28th February. The entire week provides a unique opportunity to raise awareness of key policy issues that affect amyloidosis. Patient organizations, NIH and other government entities, medical researchers, and pharmaceutical companies developing treatments for rare diseases all take part in this annual event.

The Amyloidosis Research Consortium is taking six advocates from across the country to Capitol Hill for the week, where they will learn to be effective advocates and meet with their representatives on the Hill. There they will share their personal experiences with the disease, and discuss key policy issues that impact our community.

If you are not able to join us and our advocates at Rare Disease Week in D.C., February 27th through March 2nd, you can still make your voice heard on Capitol Hill and participate in some of the programming.

Here are four ways to participate remotely:

  1. Watch the livestream of Rare Disease Day at the National Institutes of Health (NIH) on Monday, February 27th. 
  2. Watch the livestream of the Legislative Conference on Tuesday, February 28th
  3. Call your Members of Congress on Lobby Day on Wednesday, March 1st.
  4. Email your Members of Congress on Lobby Day on Wednesday, March 1st. 

All the information you need to participate including key messages to share with your members of congress, can be found here at the EveryLife Foundation Website

 

21st Century Cures Holds Promise for Amyloidosis

The Act signed into Law Brings the Patient Voice into Sharp Focus

On December 13th, President Obama signed into law the 21st Century Cures Act, a game-changing bill for medical innovation. We are very grateful to Representatives Fred Upton (R-MI) and Diana DeGette (D-CO), as well as members of their staff, for their impressive work and commitment to this bill and for incorporating the feedback from groups like ours in the rare disease community.

“Passage of the 21st Century Cures Act is the culmination of several years of hard work and advocacy by many rare disease patient advocates and patient advocacy organizations,” said Peter L. Saltonstall, President and CEO of the National Organization for Rare Disorders (NORD).  The Amyloidosis Research Consortium and our committed patient advocates are proud to have played a part in seeing this Act come into law.

The bill includes many provisions that will enhance and improve the discovery, development, and delivery of orphan therapies for rare disease patients, including:

    Streamlining of U.S. Food and Drug Administration (FDA) review of genetically targeted and protein variant therapies for rare diseases;

    Creation of funds in the amount of $4.8 billion over 10 years for the National Institutes of Health (NIH) to include funds for the Precision Medicine Initiative, and the Cancer Moonshot;

    Further expansion of the Patient-Focused Drug Development Initiative and requirements for the FDA to report on how patient experience data was used in regulatory review.

The ARC is the first patient-led foundation to hold a Patient-Focused Drug Development meeting in parallel with the FDA’s initiative. This new law rightly recognizes that patients should play an essential role in the development of drugs and devices to diagnose and treat diseases. Patients are in a unique position to provide essential insights about what it is like to live with and fight their disease. The 21st Century Cures Act will enhance these ongoing efforts to better incorporate the patient’s voice into the FDA’s decision-making process.

 

ARC Submits Guidance on Drug Development in AL Amyloidosis to FDA

 

The Amyloidosis Research Consortium (ARC) submitted a draft guidance for industry on developing drugs for AL amyloidosis to the Food and Drug Administration (FDA), to improve the design of clinical trials and accelerate the review of Potential therapies.

Patients with AL amyloidosis are often treated off-label with drugs that are indicated for the treatment of multiple myeloma.

“We are not seeing the improvement in outcomes for patients with AL amyloidosis that we are seeing in myeloma. Therapies developed and approved specifically for AL amyloidosis are vitally needed,” said Isabelle Lousada, CEO of the Amyloidosis Research Consortium. In September 2015, the ARC held a roundtable meeting of leading experts, industry representatives and members of the FDA to develop a pathway for drug development in amyloidosis.  As a result of this roundtable meeting, it was agreed that a draft guidance document should be produced. Crafting this guidance involved active participation from all stakeholder groups including patients, medical experts, academics and biopharmaceutical industry representatives.

“Barriers to developing new medicines for rare diseases like amyloidosis stem from challenges of small study populations and an evolving understanding of disease physiology, which can make clinical trial design complex,” commented Spencer Guthrie, Head of Medical Affairs at Prothena Biosciences. “Clear guidance from the expert community can help to optimize clinical trials to better meet the needs of patients.”

The guidance proposes clinical trial designs that account for the impaired cardiac and renal function in AL amyloidosis patients, and include broad patient populations with few eligibility restrictions. The guidance also encourages using free light chains (FLC) or N-terminal pro-brain natriuretic peptide (NT-proBNP) measurements as surrogate endpoints, rather than evaluating overall survival.

In November 2015, the ARC held a public meeting including patients, amyloidosis expert physicians from around the world, and regulators at the US Food and Drug Administration (FDA). More than 240 people attended, with patients communicating 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. This resulted in “The Voice of the Patient" document that the ARC released earlier this year, reflecting patient's perspectives. This publication, in concert with the draft guidance, provides multifaceted resources to improve and accelerate a drug development pathway for AL amyloidosis. 

Remembering Dale Schenk

A Pioneer in Developing Treatments for Amyloidoisis and Neurodegenerative Diseases

Dale was committed to improving patients lives. He is shown here surrounded by amyloidosis patients and caregivers, at Prothena's office in San Francisco, 2015

Dale was committed to improving patients lives. He is shown here surrounded by amyloidosis patients and caregivers, at Prothena's office in San Francisco, 2015

Dale Bernard Schenk devoted his life to understanding enough about neurological diseases, such as Alzheimer’s and Parkinson’s diseases, to conceive of innovative therapeutic strategies that are now being evaluated in multiple placebo-controlled clinical trials. These pioneering efforts have been recognized by several awards, including the American Academy of Neurology’s Potamkin Prize for research in Alzheimer’s disease. Dale died Sept. 30 at his home in Hillsborough, California, at the age of 59, from pancreatic cancer. He is survived by his wife, Elizabeth, and their children Max and Sam, and two children, Anais and Sara, from a previous marriage to Maria Torres, who died in 2005.

Dale Schenk was born May 10, 1957 in Glendora, California to Walter Bernard Schenk, a firefighter, and Rosemary Schenk, a family therapist. He received an undergraduate degree in biology in 1979 from the University of California at San Diego, where he stayed on to earn a Ph.D. in physiology and pharmacology in 1984. In 1987, Dale joined Athena Neurosciences Inc. in San Francisco, a company founded by his long-time collaborator Dennis Selkoe of Harvard University. Dale was director of neurosciences.

Schenk became very well known for his work at Athena Neurosciences and later at Elan Corporation, where he helped devise a vaccine strategy to ameliorate Alzheimer’s disease. The hypothesis being that vaccination of Alzheimer’s patients with Beta-amyloid intramuscularly would generate antibodies that would target beta-amyloid in the brain for removal. beta-Amyloid builds up in the brains of Alzheimer’s disease patients as amyloid fibrils, apparently causing the initial phase of neurodegeneration in this disease affecting ≈ 10 million patients worldwide. There were compelling indications that this novel, so-called active, immunization strategy might impede disease progression, although neuroinflammation in some patients led Dale and others to develop second-generation vaccines that did not induce neuroinflammation. Subsequent autopsies of some of the patients enrolled in the initial vaccine trial and later succumbing to unrelated causes revealed that they had less amyloid buildup in their brains, providing further evidence that removing the amyloid fibrils could offer an avenue to treat this form of dementia.

This creative and insightful work led Schenk and others to come up with the passive immunization strategy for Alzheimer’s disease—the concept of using periodic peripheral injections of tailored antibodies to remove beta-amyloid fibrils from the brain. Some of these trials showed clearance of amyloid without cognitive benefits, although many experts now believe that the patients enrolled were too late-stage to see cognitive benefits. Thus, numerous passive immunization trials are underway testing Dale’s strategy in early stage Alzheimer’s patients. There is reason to be optimistic that this innovative strategy will become a first-in-class disease-modifying approach to slow the progression of Alzheimer’s disease.

Owing to these contributions and many others, Schenk was promoted at Elan, rising to Chief Scientific Officer and Executive Vice President. Dale left Elan to co-found and lead Prothena as CEO in 2012. Prothena continues to grow, currently exhibiting a current market valuation of $2.06 billion. The company’s top development projects include passive immunization strategies to treat two different amyloid diseases: light chain amyloidosis and Parkinson’s disease, the latter in collaboration with Roche.

Dale’s creativity, humor, quick smile and steady hand in treating these very challenging neurodegenerative diseases will truly be missed by the patients, the scientists and the treating physicians. Just before co-founding Prothena, Dale initiated a close collaboration with Christopher Dobson and colleagues at Cambridge in the UK to discover a pharmacologic strategy for Parkinson’s disease and other neurodegenerative disorders.  The idea is to suppress at the earliest possible opportunity the aberrant processes through which protein aggregation results in the generation of highly toxic species, and hence to allow our natural defense mechanisms to maintain their efficacy for longer periods of time. This program has been extremely successful, and Dale was a constant source of inspiration and ideas. His regular visits to Cambridge were anticipated with great excitement by all those involved in these studies. I (CMD) last saw Dale in Sweden in July and he was as keen as ever to be brought up to date on the latest developments, and as full of suggestions as ever. With his passing we have lost a kind and generous colleague whose infectious enthusiasm and constant encouragement brought out the best in everyone with whom he worked.

You will be missed our friend.

Jeffery Kelly and Christopher Dobson

 

Dr. Jeffery Kelly is the Lita Annenberg Hazen Professor of Chemistry and Chairman, Department of Molecular and Experimental Medicine at Scripps Research Institute and a member of the ARC's Collaborative Network Steering Committee.
Professor Christopher Dobson is the John Humphrey Plummer Professor of Chemical and Structural Biology Master of St John's College, Cambridge.

Amyloidosis Voice at Global Genes Summit

Amyloidosis Voice at Global Genes Summit

On September 22nd and 23rd two members of the Amyloidosis Research Consortium were invited speakers at the Global Genes 5th Annual RARE Patient Advocacy Summit event in Huntington Beach, California. 

ARC Founder and CEO, Isabelle Lousada, delivered a presentation on The Patient's Role in Drug Discovery: Pre-Clinical Tools and described the work that is accomplished through the ARC’s collaborative network of leading experts to identify and validate biomarkers. This work is vital to improving and accelerating drug development in amyloidosis.

 

ARC Board of Directors member, Dena Heath, addressed Regulatory Advocacy: Patient Organization Case Studies on Working with the FDA. Dena presented the impressive portfolio of work that has been done through the ARC to engage the FDA and raise their understanding of amyloidosis, in order to create a better environment for evaluating novel treatments for these diseases.

 

It was an honor to be asked to speak at this outstanding RARE Patient Advocacy Summit and to be among an extraordinary group of rare disease patients and advocates, scientists, medical experts, regulatory experts, and the passionate and determined individuals and teams from rare disease organizations around the USA.

 

About Global Genes

Global Genes® is one of the leading rare disease patient advocacy organizations in the world. The non-profit organization promotes the needs of the rare disease community. What began as a grassroots movement in 2009, with just a few rare disease parent advocates and foundations, has since grown to over 500 global organizations. Learn more at: globalgenes.org

 

The Amyloidosis Research Consortium is a member of the Global Genes RARE Foundation Alliance, which is a coalition of over 300 rare disease organizations that understand that together we are more powerful. The alliance partners exchange best practices and share their lessons learned in order to drive better outcomes for the entire rare disease community, and creates a culture of collaboration to maximize  "The Power of the Collective Impact." 

Calling all Cardiologists

 

ARC is supporting a Satellite Symposium at the Heart Failure Society of America (HFSA) Meeting, 4-6pm, September 17, 2016

Cardiologists miss the diagnosis of amyloidosis more frequently than any other discipline. Don't be one of them. Join ARC for an exciting CME Satellite Symposium at HFSA, entitled Cardiac Amyloidosis: A Multidisciplinary Approach to Understanding, Diagnosis and Treatment. The distinguished panel of speakers includes:

Mark Semigran, MD Associate Professor of Medicine, Harvard Medical School, Medical Director, Heart Failure and Cardiac Transplant Program, Massachusetts General Hospital

Martha Grogan, MD Assistant Professor of Medicine, Mayo Medical School, Department of Cardiovascular Diseases, Mayo Clinic

Frederick Ruberg, MD Associate Professor of Medicine and Radiology, Boston University School of Medicine, Director, Advanced Cardiac Imaging Program Section of Cardiovascular Medicine and Amyloidosis Center, Department of Medicine, Boston Medical Center

James Stone, MD, PhD  Associate Professor of Pathology, Harvard Medical School, Head of Cardiovascular Pathology, Department of Pathology, Massachusetts General Hospital

Angela Dispenzieri, MD Professor of Medicine, Professor of Laboratory Medicine and Pathology, Mayo Medical School Division of Hematology, Department of Internal Medicine, Mayo Clinic

 

 

Seminal ARC Manuscript Published on Use of NT-proBNP as Endpoint in Pivotal Trials

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 current issue of 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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Contact:

Isabelle Lousada

Amyloidosis Research Consortium

Ilousada@arci.org

617-899-8810

Report from International Symposium on Amyloidosis

The 2016 International Symposium on Amyloidosis was held in Uppsala, Sweden in early July. Over the years the meeting has grown in size and it was impressive to see over 400 scientists and experts come together to spend three days sharing knowledge and learning more about amyloidosis. ARC’s booth, presentations and meetings highlighted the important role and achievements of the Amyloidosis Research Consortium, as well as an opportunity to bring together all stakeholders to work on collaborative initiatives moving forward.

Inaugural Meeting of ARC's Collaborative Network

ARC held a number of key meetings, bringing together industry partners, patient representatives and experts to discuss registries and research programs that will advance our knowledge and support the development of new treatments. ARC hosted the first meeting of the Collaborative Network. The network stretches across the globe, and is made up of twenty-four amyloidosis centers, each one having met rigorous criteria. The Clinical Network is focused on expediting and optimizing clinical research through efficient clinical trial design, accelerating accrual, sharing data and addressing the barriers that slow down the delivery of promising therapies. It was a great evening and we look forward to announcing the initial studies soon.

 

ARC booth

The only nonprofit organization represented by a booth, ARC Director Dena Heath staffed the booth for the duration of the conference. She spoke with doctors and scientists from around the world, sharing the ARC mission of accelerating the development of advanced diagnostic tools and effective treatments for systemic amyloidosis through collaboration and innovation.   Ms. Heath also presented the new Amyloidosis Clinical Resources App for smart phones and tablets and the two new laminated pocket cards for health care professionals – the Cardiac Alert pocket card and the Clinical Trials pocket card. 

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ARC poster

One of the challenges faced by amyloidosis is the time that it takes to get diagnosed and the number of physicians who miss the diagnosis. Resulting from the critical study ARC conducted last year identifying which specialties are most likely to miss the diagnosis, a roundtable of cardiologists was convened to identify programs to impact early and accurate diagnosis of amyloidosis. The results were shown as a poster presentation entitled Recommendations from the Amyloidosis Research Consortium Educational Roundtable at the American Cardiology Annual Meeting, April 1, 2016, by Mat Maurer, et al.

The poster was interactive with many attendees at the meeting contributing ideas to best address these initiatives.

International Patient Support Group Leader Meeting

The European patient support group leaders participating in the conference organized a joint meeting and planning session.  Countries represented included Brazil, Sweden, Spain, Portugal, France, Germany, Italy, Netherlands, Israel, and Japan. ATTR amyloidosis patient numbers are consistently higher in the EU and South American support groups than they are in the U.S.  groups.  These group leaders are working hard to build their alliances, expand their patient access, and work as a united voice for patients in their countries and in the amyloidosis community as a whole.  The ARC was invited to attend this session and to share the amyloidosis resources here in the U.S. including the new APP, the websites and the ATTR patient meeting held every other year in Chicago.