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27 FEBRUARY 2019

Listening Session with the FDA on Rare Pediatric Diseases

On November 5, 2018, the American Liver Foundation (ALF) participated in a one-hour listening session on rare pediatric liver diseases with representatives from the Food and Drug Administration (FDA). The goal of the listening session was to provide FDA officials from across the Agency – including reviewers of drugs, biologics, and medical devices – with the experiences, perspectives, needs and priorities of patients living with rare pediatric liver diseases and their caregivers.

The meeting primarily focused on patients and caregivers (names listed below) who shared:

  • Symptoms and experiences related to living with a rare pediatric liver disease
  • The impact of the condition on daily functioning and quality of life
  • Experiences with treatments
  • Preferences for treatments and outcomes

This dialogue about the patient experience was supplemented with a discussion that included representatives of the broader liver disease patient advocacy community (ALF’s Chief Executive Officer and National Director of Programs) and a clinician. Approximately 20 staff members from the FDA attended in person and another 35 participated via teleconference.


  • Tom Nealon, Esq., Chief Executive Officer, ALF
  • Jonathan Martin, National Director of Programs, ALF
  • Sanjiv Harpavat, MD PhD, Texas Children’s Hospital; Board Chair, ALF Texas Division; member, ALF Medical Advisory Committee
  • Zac Rue, biliary atresia patient, age 16
  • Heather Cline, Zac Rue’s mother
  • Alexandra Busby, progressive familial intrahepatic cholestasis (PFIC ) patient, age 8
  • Kristen Busby, Alexandra’s mother
  • Michael Busby, Alexandra’s father
  • Erica Stein, Wilson’s Disease patient and advocate (by teleconference)
  • James Valentine, JD, MHS, regulatory advisor to ALF

Patient Statements: Highlights

There are many rare pediatric liver diseases. Due to the duration and format of this listening session, select patient and caregiver representatives were chosen from a limited number of these conditions. The meeting highlighted the shared burden and struggles of living with these diseases and illuminated some of the differences in symptoms and disease progression amongst them.

  • Zac Rue (Biliary Atresia)

Zac was born four weeks early, jaundiced and with a black and blue face. Immediately, the doctors put him under bili lights, but his color did not improve so he was transferred to a different hospital where more specialists were able to examine him. Because his liver tests continued to remain abnormal, ultrasounds showed no detectable gallbladder and HIDA (hepatobiliary iminodiacetic acid) scans showed that his bile ducts were not working properly, he underwent an observatory surgery within the first days of his life.

During the 7-hour procedure, Zac was diagnosed with Biliary Atresia, a disease with no known cause or treatment. When he was one-month-old, he had a Kasai procedure to reconstruct his bile ducts. Although he was in-and-out of the hospital for an extended period as an infant, he is now an active and thriving sixteen-year-old. Unfortunately, his doctors still believe that he will most likely need a liver transplant by the time he is eighteen.

Zac first became involved with ALF in 2003, when he became the “patient match” for Tom Nealon, who was running the Boston Marathon as part of an ALF charity team. Since then, Zac has not only promoted increased liver research funding, access to care, and organ donation on Capitol Hill and beyond, he has been the inspiration for Tom to remain committed to ALF and become National Board Chair and, ultimately, CEO.

  • Alexandra Busby (PFIC)

Alexandra was quiet at birth, scratched everything she could touch, and could not sleep for even one or two hours at a time. When she was two-months-old, her parents began seeking medical help to no avail. By the time she was three-years-old, the mystery became clear: Alexandra had PFIC. She became one of approximately 10 children in a clinical trial for patients with cholestasis. Since taking the trial drug daily, she has been mostly asymptomatic and able to live a generally normal, healthy life.

Unfortunately, her younger brother was also born with PFIC and is not eligible for the trial drug. Kristen and Michael worry about how much damage is being done to his liver because he cannot go on this medication. They fear that he – and possibly his sister – will need a liver transplant. When the FDA’s pediatric hepatologist prompted the Busbys to talk more about their experience, they focused on two points: 1) The importance of keeping a patient diary that tracks drug effectiveness and side effects, and 2) Their desperation and attempts to secure treatment for their son.

  • Erica Stein (Wilson’s Disease)

Although Erica was born three-and-a-half months early and spent the first weeks of her life in intensive care, she seemed healthy until sudden abdominal pain and fainting spells at age nineteen led to an emergency liver transplant. Unbeknownst to Erica until that time, both of her parents carried the gene for Wilson’s Disease and she had suffered from it for her entire life. The disease prevents the body from filtering copper properly. Whereas a normal copper count is nine to twelve, Erica’s was over 500 at the time of her transplant. Afterwards, she underwent bile duct reconstruction surgery and had extensive physical therapy. In the eleven years that have passed since her transplant, Erika has continued to adhere to the requirements and conditions of being a transplant recipient and embarked on a career in health communications.

Erica is a former program coordinator at ALF and has continued to support the organization.

Clinician Statement: Highlights

  • Harpavat (pediatric gastroenterologist)

Treatment for pediatric liver disease is limited.

  • What will happen when the PFIC study ends? Will patients continue to have access to the trial drug? If the drug works, when will it be available for normal prescription use? These are the sorts of questions that doctors hear from patients.
  • Biliary atresia is the leading cause of liver transplant in children. Even those who are able to stave off a transplant are left wondering if they will need one down the road. As a result, new therapies are needed for those children who do not need transplant initially.
  • Wilson’s Disease therapies are expensive and difficult for most families to get. New therapies are on the horizon, but not easily available.
  • For all of these pediatric liver diseases, FDA support in developing new treatments or repurposing old medications is needed.

Rare pediatric diseases frequently are not caught early.

  • This is tragic because symptoms appear early and often get worse with age. Early diagnosis would make a huge difference.
  • There is no FDA-approved test for early diagnosis of biliary atresia or PFIC.
  • One avenue that could benefit from FDA support is development of devices/programs/tests to ensure early diagnoses.


During a follow-up discussion with the FDA representatives, the patient advocates shared the following:

  • Life with a rare pediatric liver disease is stressful because:
    • Many healthcare providers do not seem to have enough knowledge about rare pediatric liver diseases.
    • Medical professionals can be slow to recognize or identify a child’s disease.
    • The timeline for a liver transplant can be uncertain.
  • If a child has never known life without illness, he/she does not “miss” a more typical childhood.
  • ALF’s education and awareness efforts are extremely valuable.
    • Advocacy activities, like this FDA meeting, can have a big impact.
    • Families of children with pediatric liver diseases require information on diet, exercise and anything else that could optimize treatment – including suggestions on how to make injections easier – and ALF fills this need.
  • School nurses need to know what medication a child can or cannot have, e.g., ibuprofen.
  • When discussing the most pressing need (beyond better treatments):
    • Zac said he would like more education to be available on biliary atresia.
    • Zac’s mother Heather seconded this point. She worries that there is more they could be doing to help Zac, and that they just don’t have enough information.
    • Zac mentioned that he can’t do contact sports and the hepatologist said there are drugs being developed to address this issue.

On the topic of clinical trials, ALF’s patient advocates commented that:

  • When putting together a clinical trial, it is important to communicate and share information with patients/caregivers. The “unknowns” of clinical trials tend to cause apprehension.
  • It can be difficult to join clinical trials because of the challenge in finding out about active ones and various restrictions for participation.
  • It is burdensome when clinical trials require regular travel because this leads to missed work by the parent and missed school by the child.
  • Patient journey mapping is tedious, but important for documenting disease progression and treatment side effects.
  • Deciding whether to hold off on a surgical procedure to better the chances of being included in a clinical trial is a tough decision for patients and their parents to make.
    • Alexandra’s parents stated that they would hold off on a procedure if it meant that their daughter or son could be included in a clinical trial.
    • Zac’s mother Heather expressed concern about joining a clinical trial for any drug that could potentially increase the risk of liver failure.
  • When discussing whether they would enroll their children in a trial with a long-term extension and the possibility of a placebo treatment:
    • The Busby’s said they probably would.
    • Heather was not sure. She explained that she knows Zac will need a transplant at some point and she would want to know whether joining the trial would delay his need for transplant.














FDA’s Disclaimer: Discussions in FDA Rare Disease Listening Sessions are informal. All opinions, recommendations, and proposals are unofficial and nonbinding on FDA and all other participants. This report reflects the American Liver Foundation’s account of the perspectives of patients and caregivers who participated in the Rare Disease Listening Session with the FDA. To the extent possible, the terms used in this summary to describe specific manifestations of rare pediatric liver disease, health effects and impacts, and treatment experiences, reflect those of the participants. This report is not meant to be representative of the views and experiences of the entire rare pediatric liver disease patient population or any specific group of individuals or entities. There may be experiences that are not mentioned in this report.

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