FDA Approves Two Treatments for hATTR Amyloidosis in 2018

FDA Approves Two Treatments for hATTR Amyloidosis in 2018

 by Frederick L. Ruberg, MD – Boston University, BUMC, Amyloidosis Center

What a momentous Summer of 2018 it has been for transthyretin (ATTR) amyloidosis. First, in July 2018, in the same issue of the New England Journal of Medicine, two different phase 3 clinical trials were reported demonstrating the efficacy of two different pharmaceuticals as treatments for ATTR amyloidosis polyneuropathy. In randomized, double-blinded, placebo-controlled trials, each of these agents showed efficacy in slowing of progression or even improvement of peripheral neuropathy associated with hereditary ATTR (hATTR) amyloidosis.

These trials were accepted as sufficient demonstrations of efficacy to permit the US FDA to approve both patisaran or OnpattroTM (Alnylam Pharmaceuticals) and inotersen or TegsediTM (Ionis/Akcea Therapeutics) as the first treatments for ATTR amyloidosis. Both drugs were approved for hereditary ATTR amyloidosis with evidence of neuropathy. Furthermore, in August, a third phase 3 clinical trial was reported in the New England Journal of Medicine – this one describing the efficacy of yet another medication (tafamidis or VyndaqelTM, Pfizer) but tested in patients with ATTR cardiomyopathy. This trial (ATTR-ACT, Maurer MS et. al, NEJM 2018), in distinction from those above, showed that tafamidis was superior to placebo for survival among patients with congestive heart failure meaning that patients randomized to the drug lived longer than those who were not. FDA has yet to act on approval of this agent, but the community of patients and caregivers with ATTR amyloidosis with cardiomyopathy is eagerly awaiting its decision.

Each of these 3 new drugs acts through different mechanisms to achieve the same clinical objective – that is to arrest or reverse the progression of neuropathy or heart failure associated with ATTR amyloidosis. Thus, we have gone from a disease without pharmaceutical treatment (previously only treated with organ transplantation) to one where we now have 3 effective agents, albeit with different target populations, in a few short months.

Each of these new agents already approved by FDA was done so through accelerated pathways including Fast Track, Priority Review, and Breakthrough Therapy designations. In addition, the drugs have received Orphan Drug designation, which FDA defines as: “The Orphan Drug Designation Program provides orphan status to drugs and biologics which are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases/disorders that affect fewer than 200,000 people in the U.S., or that affect more than 200,000 persons but are not expected to recover the costs of developing and marketing a treatment drug.” Cost remains a key sticking point, as now that we have approved drugs, discussions/negotiations are ongoing between sponsors (ie, pharmaceutical companies) and 3rd party payors (insurers) over pricing. As a care provider for patients with ATTR amyloidosis, I am grateful that so many of our partners in industry looked to ATTR amyloidosis as a space in which to develop desperately needed treatments. Further, I think we all can agree that the sponsors which invested great resources in dollars and time should be permitted the opportunity to recover their investment. However, the cost of these new drugs, which would in theory be given for years to decades (i.e., the duration of a patient’s life), must be balanced with the cost to the patient directly, and further the cost to our healthcare system. Such decisions are even more difficult when we are speaking about individuals, with real symptoms, and real disabilities.

Determination of a drug cost naturally considers the numbers of potential patients who can be treated. If more patients can be treated, than the cost per unit can be lower for a similar return. As I noted above, FDA considers hATTR amyloidosis an Orphan disease affecting < 200,000 people at any given time, and while this appears undoubtedly true for hATTR polyneuropathy, is it also true for ATTR cardiomyopathy? A disease is rare because it truly doesn’t affect a large number of people, or it is rare because it is unrecognized. In the case of ATTR amyloidosis cardiomyopathy, which includes both hereditary and wild-type amyloidosis (ATTRwt) the answer is probably a combination of the two.

This October, in the Journal of the American College of Cardiology, a team of cardiologists and orthopedic surgeons at the Cleveland Clinic collaborated on an innovative screening study for amyloidosis. Led by Mazen Hanna, MD (Sperry BW, J Am Coll Cardiol 2018), the investigators looked at sequential patients undergoing carpal tunnel release surgery and analyzed the resected tissue under the microscope for the presence of amyloidosis. Bilateral carpal tunnel syndrome has long been associated with systemic amyloidosis, but up to this point no one has actually examined whether one could use carpal tunnel release surgery as a means to screen for the disease. The authors placed relatively few exclusions on their study population casting the broadest possible net to include all men over age 50 years, all women over age 60 years, and excluded only those with known amyloidosis, prior trauma, or rheumatoid arthritis. Of the 319 surgeries performed over the course of a year, 98 patients were included in the final analysis, and previously unrecognized amyloidosis was found in 10 total (or 10%) patients. As predicted, 100% of patients with amyloidosis had a history of bilateral carpal tunnel syndrome, but so did 83% of those without amyloidosis. What we learned from this important study is that bilateral carpal tunnel syndrome is indeed common in systemic amyloidosis, but it is also common in patients without systemic amyloidosis, so as a clinical filter it is relatively non-specific. But we also learned that unsuspected amyloidosis can be diagnosed with carpal tunnel surgery, and furthermore, amyloidosis in this population may be seen in as many as 1 in 10. Uncommon yes, but not a rare disease. So, if this rate proves accurate in larger populations, there are likely more patients with amyloidosis than currently appreciated. How many is not yet clear. Such data feed directly into the determination of cost for these promising new agents.

Another important aspect of this study is that screening afforded a means to identify patients early in their amyloidosis disease course. In fact, 3 of the 10 identified (1 case of AL amyloidosis, 1 ATTRwt, and 1 hATTR) were given amyloidosis specific therapy. Early identification is critical in any medical disease, but particularly so in the case of systemic amyloidosis where the damage done by amyloid deposits is either slow to reverse (as in the case of neuropathy) or largely irreversible (as in the case of cardiopathy) with currently available treatments. In fact, in the ATTR-ACT trial of tafamidis, those who had less severe congestive heart failure (a marker of earlier disease) did better. Unlike in cancers such as breast or prostate, we have yet to settle upon the best screening approach for amyloidosis to apply to larger populations. In addition, we know that for AL amyloidosis patients often remain undiagnosed for months to years and see many providers before the final diagnosis of amyloidosis is made correctly (Lousada I, Advances in Therapy 2015). The same is likely also true for ATTR amyloidosis. Studies showing therapeutic success in prominent medical journals, FDA approvals, and high-profile screening reports all raise awareness of amyloidosis. These advances all work synergistically to bring amyloidosis onto the clinician’s differential diagnosis when seeing potential new cases. Screening algorithms will definitively involve integration of different modalities of testing and collaboration between providers. It is now our challenge to translate these new discoveries into clinical practice.


Dr. Ruberg acknowledges consulting income from Pfizer and research support from Eidos Therapeutics.


Fall 2018 Newsletter

Fall 2018 Newsletter

Don’t miss our Fall newsletter, filled with updates and news from the Amyloidosis Foundation and the rare disease community:

  • Article by Dr. Rick Ruberg on recent FDA approvals for two hATTR amyloidosis treatments
  • Details on our fantastic 3rd Annual Pittsburgh Research Benefit
  • Introducing two AF Board Members, Daniel Lenihan, MD, FACC and Adrienne Molteni, RN
  • Our NORD Rare Summit Recap
  • 2nd Annual AF Walk/Run in Michigan a Success
  • Celebrating Kevin Sullivan and Raising Funds for Research

Read our newsletter here.

November is National Caregiver Month

November is National Caregiver Month

Did you know that more than 44 million Americans care for a family member, friend, or neighbor? Read our tips below to help caregivers take time for themselves while supporting others.

The Amyloidosis Foundation celebrates caregivers and all they do not just in November, but throughout the year.


More details from the National Alliance for Caregiving here.

Thank You Everyone for Your Support on #GivingTuesday!

Thank You Everyone for Your Support on #GivingTuesday!

The Amyloidosis Foundation is thankful for the generosity and love from our friends and donors on #GivingTuesday. You helped us surpass our goal of raising $15,000 in 24 hours (in honor of our 15th anniversary) by soaring past that with over $20,000 in online donations and Facebook fundraisers.

Over the past 15 years, the Amyloidosis Foundation has been privileged to provide over $1.97 million to medical research for the disease and to support dozens of young investigators who have presented their work at international meetings. We are so very thankful to our donors, to the patients and families and corporate sponsors who have made this effort possible and to our staff, board members and advisors who have led us in these endeavors.

If you would still like to donate, use our online link here.




3rd Annual Pittsburgh Amyloidosis Research Benefit a Smashing Success

3rd Annual Pittsburgh Amyloidosis Research Benefit a Smashing Success

Montour Heights Country Club was over-flowing with amyloidosis awareness on Friday, October 26, 2018 for our 3rd Annual Pittsburgh Amyloidosis Research Benefit. Over 100 friends and family came to support this special night, honoring the Chairwoman who started this event, Dr. Darcy Tannehill, who passed away in April. Her daughter, Courtney A. Sullivan, and son-in-law, Dr. Adam Sullivan, were the Co-Chairs this year and did an amazing job gathering silent auction gifts and over 90 bottles of wine for the annual “wine pull”.

Guests enjoyed a live jazz band, delicious hot appetizers and a gourmet meal plus the opportunity to bid on all the unique silent auction gifts. Over $53,000 was raised thanks to our generous donors and attendees, plus our event sponsors: University of Pittsburgh Medical Center, Eidos, Alnylam, Allegheny Health Network, Akcea and Takeda.

A great night was had by all and we thank the Pittsburgh community for making this annual event a success. See you next year!


Great Day for the 2nd Annual Amyloidosis Foundation Run/Walk

Great Day for the 2nd Annual Amyloidosis Foundation Run/Walk

It was a chilly start, but the sun was shining for our 2nd annual “Run for Your Life” 5k/10k event on Saturday, October 13, 2018. We had over 70 particpants plus many friends and family cheering everyone on at the beautiful Independence Oaks County Park in Clarkston, MI.

Thank you to all of our volunteers, sponsors and donors for making this such a special day. Join us next year!

Run results here.

Photographs by bib number here.





Amyloidosis Foundation Welcomes New Board Members

Amyloidosis Foundation Welcomes New Board Members

Daniel Lenihan, M.D., FACC joined the Washington University in St. Louis Department of Medicine in 2017 as a Professor in the Cardiovascular Division and Director of the Cardio-Oncology Center of Excellence. He previously directed the Clinical Research Enterprise in Cardiology at Vanderbilt University for 8 years. He is intimately involved in the latest treatment trials for cardiac amyloidosis. Dr. Leniihan is also the Chair for the amyloidosis symposium at Washington University in St. Louis on November 17, 2018 – details here.

Dr. Lenihan has been active in cardio-oncology and heart failure for nearly 20 years. The main focus of these efforts have included hemodynamic assessments, angiogenic growth factor response, novel cardiac biomarkers as well as optimal methods to prevent or detect heart failure at the earliest stage possible in patients undergoing treatment for cancer. Dr. Lenihan is at the forefront of concerted efforts to develop a viable Cardio-Oncology fellowship training program and continues to foster collaboration among a host of colleagues regionally, nationally, and throughout the world. He is the current president of the International Cardio-Oncology Society (ICOS), a professional association whose primary goal is to eliminate cardiac disease as a barrier to effective cancer therapy.

Adrienne Molteni, RN is currently at Vanderbilt University Medical Center located in Nashville, TN and works in the Infusion Center. She has been an RN for 25 years, primarily in Medical Oncology and has a personal business as a Certified Legal Nurse Consultant.

Her hobbies include horseback riding, traveling, scuba diving, hiking, playing tennis and golf. Adrienne is a Team Lead for an animal rescue/disaster response team in TN, the Wilson County Disaster Animal Response Team. She has three sons and two grandchildren.

We welcome them both to our board and look forward to their support.


Amyloidosis Symposium at Washington University in St. Louis

Amyloidosis Symposium at Washington University in St. Louis

The Amyloidosis Foundation is proud to be a partner at this event, “Contemporary Diagnosis and New Advances in the Treatment of Amyloidosis” on Saturday, November 17, 2018 at Washington University in St. Louis, MO, chaired by our Board of Director, Daniel Lenihan, MD.  This is a symposium for providers, patients and their families. Continuing Medical Education (CME) credits will be available.

Patients touched by amyloidosis and their families are invited to attend the lunch and afternoon session. The breakout sessions will allow attendees the opportunity to ask questions of various medical providers and network.

Guest faculty includes:

Morie Gertz, MD, Professor of Medicine
Mayo Clinic, Rochester, Minnesota

Jose Nativi Nicolau, MD, Assistant Professor of Medicine
University of Utah, Salt Lake City, Utah

This course is planned and designed inter-professionally by and for physicians and nurses. It is intended for physicians in cardiology, neurology, gastroenterology, oncology, hematology, nephrology, hospitialists, internists, family and general medicine as well as physician assistants, nurse practitioners and nurses.

The intended result of this activity is increased knowledge, competence, performance and skill. At the completion of the activity registrants should be able to:

•State the etiology and epidemiology of both TTR and AL amyloidosis
•Select appropriate diagnostic approach in amyloidosis
•Differentiate AL vs TTR in diagnosis of amyloidosis
•Outline current therapeutic options
•Describe current research developments in AL and TTR

Register here.

2018 Hills & Hollers Amyloidosis Fundraisers in Tennessee

2018 Hills & Hollers Amyloidosis Fundraisers in Tennessee

Join us on November 10, 2018 for the Hills & Hollers events near Nashville, TN! Present Troubles Racing, Inc., a nonprofit organization focused on raising amyloidosis awareness and supporting patients and families dealing with this disease, host this annual day of fun. The Hills and Hollers Half Marathon and 5K serves as their main fundraiser for the year.

The race begins and ends at the Burwood Community Center in rural Williamson County, TN. The Half Marathon is a looped course that features rolling hills and hollers (some call them hollows) through the communities of Burwood and Boston. The 5K is a mostly flat out and back run, sprint, or walk from the Community Center. The Hills and Hollers also includes the Little Holler Run; a .17 mile (300 Yards) fenced off course for kids 7 and younger.

Runners and thier families can also enjoy our race day silent auction with a variety of options to bid on such as gift cards, homemade baked goods, baskets, crafts, and more. The Hills and Hollers also claims to be the “best fed race in town.” There is no shortage of food and drink awaiting you at the finsh line.

They support the Amyloidosis Foundation and our mission to provide patient support, education, research and awareness.

More details on the event here.

Register here.

Amyloidosis “Rock Star”

Amyloidosis “Rock Star”

Written by Debra Payne, Wife and Caregiver

Valentine’s Day 2013, we received a call from my husband’s nephrologist. A week earlier we had no idea what a nephrologist was. And doctors don’t typically call with biopsy results the next day. Something wasn’t right.

It began when our new family doctor ran a comprehensive series of tests on all his new patients. My husband turned out to have an extremely high protein count in his urine. We were referred to a nephrologist to discover why, not for a minute imagining anything seriously wrong with him.

The nephrologist was also at a loss to explain the dramatically climbing protein count and planned a kidney biopsy the day before Valentine’s Day. Valentine’s Day, we got the call. My husband had been diagnosed with an extremely rare blood disorder called amyloidosis, AL amyloidosis in particular. The doctor wanted to send samples to Mayo Clinic for verification and referred us for immediate treatment to a local oncologist at Rocky Mountain Cancer Center in Longmont, Colorado. 

In shock, we tried to learn everything we could about amyloidosis. One of the first things we read was that patients had a 12 to 15-month survival rate. That was devastating. We learned as much as we could about the process in as simple terms as we could understand and explain to family and friends: the body spontaneously producing a folded protein that clogs the organs reducing their ability to function. The organ most impacted in my husband were his kidneys.

The oncologist advised us not to read anything on the internet relating to amyloidosis unless it was from Mayo Clinic or another reliable cancer site. He explained treatment: low dose chemotherapy to disrupt the production of the folded proteins and an autologous stem cell transplant at Presbyterian Saint Luke’s in Denver, Colorado, to hopefully reset the body’s protein producing systems. The entire treatment seemed unimaginably frightening to us. We could only focus on baby steps.

We went through 11 weeks of low dose chemo while my husband continued to work a full-time job. I found a job with medical insurance in case my husband became permanently disabled. He went through hospital pre-testing to make sure his heart would hold up under the high dose chemo; surgical insertion of a tunneled catheter for the injection of chemo, the removal and reinsertion of stem cells, and medications; going on short term disability for 2 doses of high dose chemo, a month-long hospital stay and, because of his amazing results, only another month of recuperation at home.

The scope of concerns was unending. We worried about insurance and paychecks and prescription costs. We worried about disability and qualifying for experimental studies. We worried about doctors and their success rates with this disease and survival of the treatment and side effects. We worried about bills, medical-caused bankruptcy, and charges for required tests not covered by insurance. We worried about jobs and taking time off and driving back and forth to hospitals while maintaining a household. And overall the most pressing concern: we worried about whether he was going to survive this illness and the treatment.

The blur of hospital tests, treatments, and frantic phone calls are as raw today as five years ago. But the doctors refer to my husband as a “rock star”, saying he didn’t read how this illness was supposed to go and just made his own recovery back to good health. His protein count went from uncountable at one point to well within normal range, kidney function returned to normal range, and no sign of amyloidosis today.