Individuals with Barth Syndrome Chart New Path for the Review of Drugs

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Barth Syndrome Foundation’s recent listening session with FDA sheds light on one rare disease community’s acceptance of less certainty of treatment benefits

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“Before Barth syndrome, to my knowledge, no patient community has specifically discussed the degree of uncertainty it would accept for potential new drugs.

Barth Syndrome Foundation (BSF) shares initial reactions today to a historic dialogue held in a recent listening session with the U.S. Food and Drug Administration (FDA). The March 3rd, 2021 FDA listening session was requested by members of the Barth syndrome community earlier this year following submission of a global petition. The meeting was a first-of-its-kind and a significant milestone in BSF’s multi-year strategic advocacy agenda that spotlights the patient voice as part of the drug development and regulatory approval process.

“Our community faces significant loss of life each year to consequences of this rare and devastating disease,” says Emily Milligan, MPH, BSF’s Executive Director. “In addition to other serious and life-limiting aspects of the disease, cardiac complications such as heart failure and life-threatening arrythmias are difficult to manage and significantly alter quality and length of life for those who are affected. We believe active engagement with FDA to raise awareness of the patient perspective is critical. Absolutely no one has the ability to better communicate the impact of living with a disease, or speak to risk tolerance, than the patient or the caregiver.”

The passage of the 21st Century Cures Act of 2016 made considerable advances in updating FDA’s regulatory review process to include the patient voice. To inform FDA and other stakeholders about the impacts of living with Barth syndrome and the needs for approved treatments, BSF hosted an externally-led Patient Focused Drug Development (EL-PFDD) meeting in 2018 – the first to be held outside the Washington DC area. Over 25% of the global known living population of people with Barth syndrome participated in the meeting. Since then, BSF has continued to focus on bringing patients’ voices to the forefront of drug development decision-making processes.

Kate McCurdy, BSF’s Board chair and co-founder recognizes the adversity that families with Barth syndrome face and the opportunity for BSF to have an impact. “We are tireless because we believe there are very real opportunities for us to advance research not only in Barth syndrome but also in areas that overlap with other diseases. The most important thing we can do is provide a roadmap to hope and make sure our family’s voices are heard. Without treatments, we strip the potential of every child to become a brilliant and contributing young person, of every affected adult to be able to work, to get an education, to have a decent quality of life. Uncertainty is not something that we are afraid of. We live with it every day.”

This most recent dialogue between the Barth syndrome community and members of various groups within the FDA (including those from the Division of Cardiology and Nephrology and the Division Rare Diseases and Medical Genetics in the Center for Drug Evaluation and Research - CDER, as well as representatives from the Center for Biologics Evaluation and Research - CBER) showcases ways in which BSF is pioneering new territory in rare disease drug development and approval. This FDA listening session, while focused on the cardiac aspects of Barth syndrome, helped demonstrate more broadly how people with rare diseases share unique attitudes toward acceptance of less certainty when considering benefits. Darryl, a young adult who suffers from Barth syndrome, who participated in the listening session, shares his perspective. “I understand that, even if a drug has gone through a clinical trial, it doesn’t necessarily mean that a clinical benefit is guaranteed. I understand that there may be unknowns when the drug has only been studied in a very small number of people because my condition is so rare. I even understand that a drug might help some people feel better, but it might not help me. But I still want to try. I’ll keep trying. I am steadfast in my willingness to try because I literally have no other options, and I want to live.”

The emphasis on acceptance of less certainty when considering the clinical benefit of therapies was a first in FDA listening sessions, not only for Barth syndrome but for all rare diseases. Uncertainty is something FDA has long-recognized in its regulations at 21 CFR 312.80, which calls for flexibility in applying its approval standards to drugs for life-threatening and severely debilitating diseases, especially where there is no satisfactory alternative therapy. In December 2019 guidance, FDA reaffirmed that less certainty about effectiveness may be acceptable, especially in rare disease settings. “To my knowledge, before Barth syndrome, no patient community has specifically discussed the degree of uncertainty it would accept for potential new drugs. This builds on the important input this community provided at the EL-PFDD meeting, which helped describe the seriousness of Barth and its dire unmet medical need from the patient perspective. Together, this understanding of the patient experience and patients’ expectations will help FDA apply its regulatory framework in a tailored and appropriately flexible way,” says James Valentine, food and drug lawyer at Hyman, Phelps & McNamara, P.C.

Barth Syndrome Foundation is grateful to all the listening session participants, including the affected individuals, caregivers and bereaved parents who bravely shared their stories, as well as members of FDA who posed thoughtful questions and listened in earnest in order to better understand the perspectives of patients with the rare disease Barth syndrome.

Barth Syndrome Foundation ( and our international affiliates comprise the only global network of families, healthcare providers, and researchers solely driven by the mission to save lives through education, advances in treatment and finding a cure for Barth syndrome. Considered a role model in rare disease advocacy, BSF has funded nearly $5.6M USD since 2002 and catalyzed over $26M USD in funding from other agencies to advance global scientific discoveries to end the suffering and loss of life from Barth syndrome. Additionally, BSF provides a lifeline to families and individuals living with Barth syndrome around the world, offering individualized support, educational conferences, a patient registry and collaborations with specialist healthcare providers to define standards of care, treatment and rapid diagnosis.

Barth syndrome is a rare, life-threatening, genetic mitochondrial disorder primarily affecting males. Affected individuals may suffer from heart failure and cardiac arrhythmia issues, muscle weakness, and infection (caused by neutropenia). Additional characteristics of the syndrome commonly include growth delay, extreme fatigue, feeding problems, impaired lipid metabolism, and cardiolipin deficiency. In some individuals affected by Barth syndrome, the symptoms can be very severe, resulting in heart transplantation, potentially lethal infections, and death.

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