Rare disease market research that captures the voice of the patient is indispensable for understanding a rare disease market. Moreover, because treatment planning for rare diseases is often a process of shared decision-making between the patient and their physician, it is critical to understand the patient voice and their journey with their disease. Fortunately, rare disease patient advocacy groups, companies that form communities for rare disease patients to share their experiences, and the U.S. Food and Drug Administration (FDA) have turned up the volume on the rare disease patient’s voice.
The Food and Drug Administration (FDA) launched the Patient Listening Sessions initiative in 2018 as a multipurpose resource for patients, advocates, and the pharmaceutical industry. In the sessions, patients and caregivers speak directly with FDA staff and share their experiences living with a disease and opinions on clinically relevant topics (e.g., treatment unmet needs, clinical trials, emerging and novel therapeutic approaches). Importantly, these patient listening sessions are an invaluable channel for drug developers to gain firsthand understanding of the rare disease patient experience, their treatment priorities, and their receptivity to clinical trial participation and innovative therapies (e.g., gene therapy.).
Several Listening Sessions have been conducted on rare diseases such as Fabry disease, progressive multifocal leukoencephalopathy, and the subject of today’s summary: Glycogen Storage Disease Type 1a (GSD1a). In this article we highlight the key takeaways from the March 25, 2021, session that heard from 5 adult patients living with GSD1a, and 1 patient caregiver.
GSD Type 1a is a genetic disease that occurs in approximately 1 in 100,000 births, and an estimated 36 births in the U.S. in 2020. The incidence is notably higher among the Ashkenazi Jewish population, where it occurs in around 1 of 20,000 individuals. Individuals with GSD1a are born with mutations in their G6PC gene, leading to a deficiency in glucose-6-phosphatase (GP6ase), an integral enzyme responsible for converting glycogen to glucose (i.e., sugar). In the absence of the GP6ase enzyme, patients have pathological storage of glycogen in organs and tissues and experience low blood sugar (hypoglycemia) and ensuing dysfunction of major organs including the liver, kidneys, and small intestine. Current treatment for GSD1a is comprised of dietary changes to maintain normal glucose levels and reduce hypoglycemia; there are no pharmacologic treatments for the disease. Patients will eat many small meals and consume cornstarch several times a day to try to reduce the degree of hypoglycemia.
Drug development for GSD1a is concentrated to a handful of companies, including Ultragenyx developing the DTX401 gene therapy for the condition, and CRISPR and Moderna with pre-clinical programs underway. As current and emerging developers of therapies for GSD1a, understanding the patient experience and receptivity to innovative gene therapies will be paramount. Herein, we summarize key takeaways from the FDA’s March 2021 patient listening session for GSD1a.
- A desire for improved quality of life is a key driver for GSD1a patient participation in clinical trials.
Most patients were open to participating in a clinical trial of either kind. The main driver of this opinion was the potential for a clinical trial to improve quality of life. If the trial was accompanied by life-threatening or long-term risks, patient opinions were split; for half of the patients, the benefits of an improved quality of life offered by new therapies outweighed the risks, especially if the risks were not long-term.
- GSD1a patient receptivity to gene therapy is high.
Patients are more inclined to try the therapy than not, on the condition that gene therapy could potentially mitigate the burden of disease. Patients pointed to a reduced need for cornstarch intake, reduced hospitalizations, and an improved quality of life as factors that would sway them towards gene therapy. The main concern from patients was the potential side effects of gene therapy or an experimental drug, which factors significantly in their willingness to participate in clinical trials. Kidney issues, liver problems, and changes to reproductive health in female patients were the potential side effects of novel treatments that are top of mind.
- Patients cite key unmet needs that, if addressed, can have a transformative impact on their lives.
Living with GSD1a can dramatically impact a patient’s quality of life, including the strict dietary requirements required to maintain normal blood glucose levels, and severe complications in adults that can lead to impaired kidney and liver function and hospitalizations. The strict dietary requirements and rigidity of eating schedules and food content can be a significant drag on the patient’s social interactions which also impacts their quality of life. Given this context, it is not surprising that the top unmet need shared by patients is long-term improvements in quality of life through reducing hypoglycemia and hospitalizations.