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Background Classic Galactosemia is a rare, autosomal recessive disease in which galactose is not metabolized properly due to severe deficiency/absence of the galactose-1-phosphate uridylyltransferase (GALT) enzyme, converting to an aberrant and toxic metabolite, galactitol. Living with the debilitating symptoms and long-term consequences of Classic Galactosemia creates a heavy burden on patients’ and their families’ lives. Objectives were to: (1) Evaluate the impact and burden of disease; (2) Qualitatively explore changes in patient symptoms following treatment; and (3) Document the meaningfulness of changes resulting from treatment with govorestat as assessed by the Caregiver Global Impression of Severity (CGIS) and Caregiver Global Impression of Change (CGIC) scales. Methodology The AT-007-1002 clinical trial involved a Phase 1/2 dose escalation component (Part A) followed by a Phase 3, randomized, double-blind, placebo-controlled long-term administration component (Part B) that evaluated potential clinical benefit. Exit Interviews were completed prior to unblinding of data. The in-depth, qualitative interviews were semi-structured, using a discussion guide, and conducted by either Zoom or GoToMeeting. Thirty-six caregiver interviews were conducted, capturing the experience of 37 pediatric patients (one caregiver had 2 patients enrolled in the study). Thematic analysis was undertaken to identify themes or patterns within the data. All analyses were conducted on blinded data. Following finalization of the analysis and report findings, post-hoc analysis of the unblinded data was then conducted to explore the meaningfulness of patients experience by treatment arm. Results This study confirms the substantial burden known to be associated with Classic Galactosemia in a pediatric population. The difficulties experienced were across multiple areas including cognitive function, behavior/social function, motor function, emotional function, communication, vision problems, ovarian insufficiency, sensory difficulties, and sleep problems. The interviews demonstrated that most patients (approximately two thirds) experienced an improvement in symptoms and impacts associated with classic galactosemia over the course of the trial. Nearly all caregivers reported that they perceived a 1-category change on the Caregiver Global Impression of Severity or Caregiver Global Impression of Change items, indicating severity and change respectively, was meaningful to them and the patient. Unblinded analysis of the exit interview data confirmed the patient experience reported by caregivers was different between the treatment arms, providing qualitative support for the treatment benefit of govorestat when compared to placebo. Furthermore, the qualitative data from caregivers provide in-depth insights of their unique lived experience that highlight the substantial impact that this improvement had on the caregiver’s and the patient’s quality of life. The improvements observed led to a reduction on the burden of Classic Galactosemia and may lead to a greater patient’s greater independence. Conclusions The exit interviews confirmed the burden of Classic Galactosemia disease across multiple domains. Qualitative investigation suggests that observed changes are meaningful to the patient and caregiver, and changes were more commonly reported in those receiving govorestat compared to placebo. Full clinical trial findings will be published separately.

Background Classic Galactosemia is a rare, autosomal recessive disease in which galactose is not metabolized properly due to severe deficiency/absence of the galactose-1-phosphate uridylyltransferase (GALT) enzyme, converting to an aberrant and toxic metabolite, galactitol. Newborn screening and timely galactose-restricted diet can resolve acute symptoms and decrease fatalities. However, despite this, significant chronic, progressive morbidities remain which have a real impact upon daily life. To better understand the burden of disease, 20 in-depth qualitative interviews were undertaken with adult patients (n = 12), and their caregivers (n = 8), enrolled in the ACTION-Galactosemia trial, part of a clinical program designed to investigate the safety and efficacy of AT-007 (govorestat) in reducing toxic galactitol and long-term clinical outcomes in Classic Galactosemia. Results Interviews revealed the substantial burden of Classic Galactosemia on patients and families. Most adults were not able to live independently, and all required support with day-to-day activities. Short- and long-term memory difficulties and tremors were identified as the most frequently experienced and challenging symptoms. Other difficulties such as fine motor skills and slow/slurred speech contribute to the significant impact on daily activities, affecting ability to communicate and interact with others. Symptoms were first noticed in early childhood and worsened with age. Classic Galactosemia impacted all areas of daily functioning and quality of life, leading to social isolation, anxiety, anger/frustration and depression. This demonstrates the significant burden of disease and challenges associated with Classic Galactosemia. Conclusions The impact on both patients and caregivers underscores the severity of the unmet medical need and the importance of pharmacological intervention to halt or prevent disease progression. Any treatment that could reduce symptoms or slow functional decline would ease the burden of this condition on patients and caregivers.

Background Classic Galactosemia (CG) is a rare, autosomal recessive condition. Newborn screening and a timely galactose-restricted diet can resolve acute symptoms and decrease fatalities, but significant chronic, progressive morbidities remain and significantly impact daily life. The objective of this study was to better understand the burden of disease in children and adults with CGs and describe how morbidities evolve over time. Methods A total of 49 individuals with CG from the United States (US) were included in the qualitative surveys (13 adults [9 self-reported] and 36 pediatric patients). Fifteen follow-up interviews were conducted with 5 adults and 10 caregivers, discussing 17 individuals with CG overall (2 caregivers each discussed 2 children). Results Qualitative survey and interview data demonstrated the substantial burden of CG. Difficulties in a wide range of functions were experienced, which included: speech articulation; language and communication; cognition, memory and learning; emotions; and social interactions. Most difficulties appeared in childhood and persisted or worsened with age. Most adults did not live independently. Others lived semi-independently and experienced many daily challenges and required support. Caregivers also described the burden of caring for someone with CG and spoke about the impact this has on their day-to-day life, work, and relationships. Conclusions These findings demonstrate the pronounced and persistent burden of disease encountered by individuals with CG, and that the condition has a significant impact on the quality of life of caregivers.