Daybue shows real-world benefits for Rett syndrome patients: Study
Improvements seen in nonverbal communication, alertness in children, adults
One year of daily Daybue (trofinetide) treatment led to improvements in behaviors such as nonverbal communication, alertness, and social interaction and connectedness among children and adults with Rett syndrome.
That’s according to published interim data from Acadia Pharmaceuticals‘ Phase 4 LOTUS study that assessed the safety and effectiveness of the approved oral therapy in 227 Rett patients, ages 1 to 60, in real-world clinical practice. Treatment was also tied to modest improvements in patients’ quality of life.
“These findings from LOTUS help deepen our understanding of the potential outcomes associated with long-term treatment of [Daybue] in the real-world setting,” Ponni Subbiah, MD, senior vice president, global head of medical affairs, and chief medical officer at Acadia, said in a company press release. “It’s particularly gratifying to document improvements in adult patients, knowing that they may have waited decades without knowing if a treatment would become available within their lifetime.”
Trial details are described in the study, “Real-world benefits and tolerability of trofinetide for the treatment of Rett syndrome: The LOTUS study,” published in Developmental Medicine & Child Neurology.
LOTUS investigates outcomes of broader Rett patient population
Daybue, given twice daily as a liquid, is approved in the U.S. and Canada for adults and children at least 2 years old with Rett syndrome. It’s thought to reduce inflammation and promote the connections between nerve cells that are impaired in Rett and drive its behavioral symptoms.
The therapy’s approval was supported by data from the Phase 3 LAVENDER clinical trial (NCT04181723), which showed that Daybue significantly eased neurobehavioral symptoms in Rett patients, ages 5 years to 20 years.
The Phase 2/3 DAFFODIL study (NCT04988867) showed that 1.5 years of Daybue safely improved communication, eye contact, and hand use in 15 girls, ages 2-4, with Rett syndrome. Most participants experienced diarrhea as a side effect of Daybue.
LOTUS, sponsored by Acadia, is an ongoing real-world Phase 4 observational study designed to investigate the outcomes of a broader Rett patient population taking Daybue over one year of real-world practice. A Phase 4 study, also called a post-marketing surveillance study, evaluates an already approved and marketed treatment to monitor its long-term safety and effectiveness in real-world settings.
Quality of life was also enhanced after one year of Daybue
In total, 227 Rett patients were included in this analysis, nearly all of whom were female (96.9%). At week one, the median dose was 36% of the approved weight-based dose, and by week 10 and beyond, the median dose was at least 80% of the labeled dose.
According to the interim analysis, 71% to 90% of caregivers reported improvements in at least one behavioral symptom during one to 12 months of treatment, as assessed by the behavioral improvement questionnaire (BIQ). Overall, behavioral symptoms were either maintained or improved compared with before Daybue treatment.
The most frequently improved behaviors were in nonverbal communication (48% to 71%), alertness (44% to 70%), and social interaction and connectedness (33% to 58%). Other benefits reported in fewer patients included improved muscle tone and breathing (16% each).
Quality of life was also enhanced after one year of Daybue, as indicated by a rise in the median score from 55.1 points to 64.9 points on the Quality of Life Inventory-Disability (QI-Disability) questionnaire. Similarly, the median change in QI-Disability total score ranged from 4.7 at one month to 4.6 at one year, “indicating improvement consistency across the follow-up,” the team wrote.
Similar trends were observed for individual domain scores of the QI-Disability questionnaire, including in social interaction, physical health, independence, positive and negative emotions, and leisure and the outdoors.
Of the 145 adverse events reported by 60 patients (26.4%), the most common were diarrhea (12.3%), vomiting (6.6%), and constipation (3.1%). Ten patients (4.4%) reported serious adverse events, with the most common being dehydration (1.3%) and diarrhea (1.3%).
After 12 months of trofinetide [Daybue] treatment in a real-world setting, improvements were evident across multiple domains of the BIQ, which provides further evidence that trofinetide treats the core symptoms associated with [Rett] as reported in clinical studies.
The occurrence of diarrhea, mostly contained inside the patient’s diaper, varied from weeks one to 12 (23% to 50%) and months four to 12 (26% to 38%). Diarrhea was managed by using antidiarrheal medication, avoiding constipation medications, increasing fluid intake, and consuming supplementary fiber.
Caregivers reported normal stools over the last three days immediately before completing a gastrointestinal assessment from weeks one to 12 (43% to 54%) and months four to 12 (55% to 63%).
According to Acadia, limitations of the present results include missing data and relying solely on caregiver reports. LOTUS participants who complete one year of Daybue have the option to continue treatment for an additional 12 months, per Acadia.
“After 12 months of trofinetide [Daybue] treatment in a real-world setting, improvements were evident across multiple domains of the BIQ, which provides further evidence that trofinetide treats the core symptoms associated with [Rett] as reported in clinical studies,” the researchers wrote.
The study also provides new scientific insights, Subbiah added.
“The data are supportive of what we’ve seen in [Daybue] clinical trials and offer new scientific insights to clinicians that improvements in Rett syndrome signs and symptoms are possible among a broadly inclusive sample of Rett patients,” Subbiah said.
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