Read the FDA Report
Fibrodysplasia Ossificans Progressiva (FOP)
Session Date: May 29, 2019
Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare disorder affecting approximately 900 people worldwide. On May 29, 2019, the International FOP Association (IFOPA), a global patient association, along with members from the FOP community, participated in a one-hour listening session with representatives from the U.S. Food and Drug Administration (FDA). The goal of the listening session was to provide FDA officials with the experiences, perspectives, needs and treatment priorities of people living with FOP.
The focus of the meeting was on people with FOP and caregivers who shared:
- Their journey of reaching a diagnosis for FOP
- Symptoms and experiences related to living with FOP
- The impact of FOP on daily functioning, quality of life and economic expenditures
- Preferences for treatments and outcomes
This dialogue about the patient experience was supplemented with a discussion from the IFOPA about the FOP Registry, which is an observational study collecting longitudinal medical data about FOP.
FOP community participants at the FDA Listening Session included:
- Joshua Scoble, person with FOP
- Stacy Scoble, mother of Joshua
- Chrissy Flexer, Joshua’s aunt
- AJ Gonzales, person with FOP
- Kristi Gonzales, mother of AJ
- Alexis Gonzales, sister of AJ
- Natalie McGuire, person with FOP
- Keegan McGuire, Natalie’s brother
- Danie Coyne, person with FOP
- Samantha Coyne, Danie’s sister-in-law
- Brian Harwell, person with FOP
- Barbara Harwell, mother of Brian
- Adam Sherman, Research Director, IFOPA
- Michelle Davis, Executive Director, IFOPA
FDA Divisions Represented
Center for Drug Evaluation and Research (CDER):
Office of New Drugs (OND):
- Office of Drug Evaluation II (ODE II), Division of Metabolism and Endocrinology Products (DMEP)
- Office of Drug Evaluation III (ODE III), Division of Bone, Reproductive and Urologic Products (DBRUP)
- Office of Drug Evaluation IV (ODE IV), Division of Pediatric and Maternal Health (DPMH)
- Office of Translational Sciences (OTS)
- Office of Biostatistics (OB)
- Division of Biometrics III (DBIII)
- Rare Diseases Program
- Professional Affairs and Stakeholder Engagement
Center for Biologics Evaluation and Research (CBER):
- Office of the Center Director
- Office of Tissues and Advanced Therapies, (OTAT)
- Division of Clinical Evaluation and Pharmacology/Toxicology (DCEPT)
Center for Devices and Radiological Health (CDRH):
- Office of the Center Director
Office of the Commissioner (OC):
- Office of Clinical Policy and Programs (OCPP)
- OCPP, Patient Affairs Staff (PAS)
- OCPP, Office of Orphan Products Development (OOPD)
Summary of Topics Discussed
Members from the FOP community shared their stories about living with FOP and illuminated some of the differences in symptoms and disease progression. Select highlights from people living with the disease and their family members are provided below.
The path to a correct diagnosis can be lengthy, as FOP is a very rare disease and many healthcare providers are unaware of FOP’s hallmark signs and symptoms. A mother of a boy with FOP retold the long process of obtaining a correct diagnosis, “[My son] saw numerous specialists. He was diagnosed with mental retardation, autism, and more. None of these diagnoses were true. It wasn’t until [my son] saw a neuro-geneticist that he was correctly diagnosed. By this time, he had already had 3 surgeries. Surgeries he never should have had.” Another person with FOP described his difficult journey to receiving a diagnosis, “I first showed signs of FOP when I was 5 years old. I had a swelling on my left shoulder, which the doctors thought was cancer. During the operation to remove what they thought was a tumor, they believed the cancer had spread to my lymph nodes and they wanted to remove my entire left arm. Luckily for me during one of the consultations a doctor who was familiar with FOP asked to see an x-ray of my toes and upon seeing my malformed big toes he correctly diagnosed me with FOP.”
- Once diagnosed, personal life choices are often altered to accommodate the physical limitations of FOP. Many with FOP hold back on their personal life ambitions for fear of further disease progression. As one person with FOP described this concern, “I want to make goals and achieve my dreams, but I’ll admit that the fear of awakening the FOP bear again does make me cautious. I don’t want to lose any more movement. I don’t want to go through those crushing feelings again.” Another individual commented on how FOP impacted her future dreams, “The physical pain during this time was hard, but I almost think the emotional pain was worse. To see the plan for my life crumble and to be forced to give up my independence, give up some dreams, leave the amazing friends I made, and leave the family that I had was a huge struggle.” People with FOP often refrain from certain activities due to either fear of eliciting more heterotopic bone growth or due to their own physical limitation. “In addition to the big changes that FOP has brought upon my life, it ultimately impacts my every action and thought. I try not to pay attention to what it does all the time, but at the end of the day it is right there in the driver’s seat making my life decisions.”
Many living with FOP experience persistent, uncontrolled pain. A mother described unrelenting episodic pain for her son, “He also has had episodes of extreme pain when lying down at night for about 2 years. He will typically scream out in pain every hour during these episodes. There is nothing worse than hearing your son crying out in excruciating pain and asking you to make the pain go away.” Another mother described the severe pain and swelling her son experiences, “[He] has severe migraines from the pressure in his neck from the bone growth that is causing swelling in his brain which is then pressing on his optical nerves causing blurry vision. This along with pain, swellings and flare-ups.”
FOP impacts those living with the disease as well as family members. One mother shared about the sacrifices that are often required by a family to support a child with FOP, “I had to find a job which had flexibility to allow me to take time weekly for [my son] to go to the doctors and to therapy. We are at our local children’s hospital 1-2 days a week seeing one of 10 specialists: cardiology, oncology, pulmonology, ophthalmology, neuro-ophthalmology, neurology, gastroenterology, ENT, rehabilitation therapy, FOP specialists, occupational therapy, aquatic therapy and speech therapy.” Another mother described how day to day and nightly activities become focused around the care for her son, which involved helping him with dressing, bathing, picking up items, and using the bathroom. “He needs help to sit down as well as assistance with standing. He is unable to roll himself at night; therefore, we are up every 2 hours or more to rotate him.”
FOP is an economic burden for those with FOP, as additional care is required for daily living. One FOP parent commented, “My husband and I both gave up our careers, we had to file for bankruptcy to save our home from the medical expenses. We fought for 3 years and made 9 visits fighting for Medically Needy Medicaid to help in addition to our primary insurance to get his medical coverage under control.” One person with FOP mentioned that he required a service to help him get dressed and undressed and to take him to and from work, at a cost of $100 per day. Furthermore, costly modifications to a home are often required to accommodate the assistive devices that many with FOP utilize. “My limited mobility and progressing flare ups has required home modifications such as entry ramps, a kitchen remodel, a bathroom remodel, customized furniture, and home automation.” A mother also described the inevitable changes that were required to accommodate someone growing up with FOP. “Suddenly we were trapped in our home. Moving from room to room became difficult. Doorways were not wide enough, cabinets were not accessible, and his bed was not low enough. He could not fit into the bathroom with his chair or get into the bathtub. He could no longer walk up or down a step.”
Any treatment that either halts or slows the progression of FOP would be life-altering. One person with FOP commented, “If there was a treatment that could stabilize my FOP and freeze it as it is now, I could continue to lead a fairly independent and fulfilling life.” A mother of a son with FOP is also looking for a treatment that can stop this progressive disease. “If you were to ask me 5 years ago what I would want, it would be a cure. Now, I just want a medicine to slow this aggressive beast down to give my baby a fair chance to be the awesome kid that he is.” Another individual with FOP commented on how a treatment would affect her life decisions, “Overall, the best aspect of a treatment that stabilizes FOP would be the ease of the constant pressure I put on myself to balance my present with my future. No longer will I have to worry about whether or not I should be prioritizing my short-term happiness over long-term happiness.” Finally, a person with FOP wanted a treatment to preserve her independence. “If there was a treatment that could stabilize my FOP and freeze it as it is now, I could continue to leave a fairly independent and fulfilling life. I only need assistance with washing my hair which I can hire someone to do a few times a week.”
As with any progressive disease, there is an extreme sense of urgency in the FOP community for a treatment that is both safe and effective. As one person with FOP commented, “If it [FOP] gets worse, there are certain foods that I will no longer be able to eat and my voice may change permanently.” A mother of a boy with FOP felt that “Keeping the progression of FOP in [my son] as is, is crucial. There is nothing more important to me than stopping the progression of FOP.”
- For some in the FOP community, they would like a treatment that enables surgery to free up restricted joints. “For me, and for others in a similar stage of life, I want a medication that stops FOP. I want a medication that stops FOP for one purpose, surgery. Surgery is the only way that my quality of life is going to improve. Unlocking my joints and giving me mobility will return my independence and my freedom that FOP took 20 years ago. I may not ever be able to play golf or drive a car or do any of the hundreds of other things I have wished I could do, but if I could take care of myself and do basic things that every person in this room who does not have FOP can do, then I would call that a huge success.”
The IFOPA presented an overview of the FOP Registry to members of FDA. The FOP Registry is an international, voluntary, observational study that captures demographic, healthcare resource utilization, and disease information directly from people with FOP via a secure web-based tool and from physicians who are caring for these patients.
- The FOP Registry has a governance structure, including a Medical Advisory Board to guide its conduct. The Medical Advisory Board is comprised of approximately 15 FOP experts from around the world, as well as representatives from sponsoring biopharmaceutical companies developing drugs for FOP.
- The FOP Registry, which now includes a patient and medical portal, will help advance our understanding of FOP, enhance clinical care, and facilitate clinical trial designs. The medical portal has the capacity to include radiological images from registry participants; the IFOPA is actively working to secure as much imaging data as possible.
- To encourage global participation, the FOP Registry is available in seven languages. The registry currently has approximately 40% of known people with FOP participating worldwide in the Registry.
- IFOPA believes there are too few people living with FOP to support multiple disease registries in FOP and would dilute the robustness of this dataset. The FOP Registry is adaptable to accommodate any future post marketing commitments, should the need for post approval data collection arise. Furthermore, data from the Registry is available to any researcher interested in studying FOP.
- The FOP Registry was launched in July 2015 and the longitudinal dataset is becoming more comprehensive and robust with each passing year. The data from the FOP Registry will be published in the coming year(s).
- The IFOPA offered to share case report forms from the FOP Registry as well as the captured data with FDA.
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 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 FOP, 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 FOP patient population or any specific group of individuals or entities. There may be experiences that are not mentioned in this report.