Clinical Data from Open-Label DAFFODIL™ Study Evaluating Long-term Safety of DAYBUE® (trofinetide) in Patients with Rett Syndrome Published in Med
-- Study supported FDA and Health Canada approvals of DAYBUE for treatment of Rett syndrome in patients ages two years and older
-- Results consistent with Phase 3 LAVENDER™ and open-label LILAC™ studies
“Rett syndrome is a debilitating condition that often causes patients to lose acquired communication and motor skills starting as early as six to 18 months old which presents significant challenges for these children and their families,” said Alan Percy, M.D., Professor of Pediatrics, Neurology, Neurobiology, Genetics, and Psychology at University of
“The final DAFFODIL results provide critical insights into the safety and tolerability of DAYBUE in younger pediatric Rett syndrome patients, including effective strategies to mitigate common side effects of treatment,” said Ponni Subbiah, M.D., M.P.H., Acadia’s Senior Vice President, Global Head of Medical Affairs and Chief Medical Officer. “These findings, along with the caregiver exit interview feedback from the study, further our understanding of trofinetide’s role in managing this complex condition and the potential benefits of longer-term treatment.”
Diarrhea (
The following exploratory efficacy endpoints supported symptom improvement:
- Clinical Global Impression–Improvement (CGI-I) scale score (7-point scale where 1 is “very much improved” and 7 is “very much worse”) was 3.3 ± 0.19 (mean ± standard error) at Week 4 and continued to improve to 2.2 ± 0.22 at Week 78.
- Caregiver Global Impression–Improvement (CaGI-I) scale score (5-point scale where 1 is “much improved” and 5 is “much worse”) at Week 12 (2.3 ± 0.12) and Week 78 (2.1 ± 0.31) indicated improvement compared with baseline.
- Impact of Childhood Neurologic Disability-Quality of Life (ICND-QoL) scale (6-point scale where 1 is “poor” and 6 is “excellent”) increased from baseline to Week 78 (3.9 ± 0.24 to 4.6 ± 0.31).
Caregivers (n = 7) who participated in the study exit interviews most frequently identified inability to communicate as the most impactful symptom of Rett syndrome (
About Rett Syndrome
Rett syndrome is a rare, complex, neurodevelopmental disorder that may occur over four stages and occurs in approximately one of every 10,000 to 15,000 female births worldwide.1-3 In the
Symptoms of Rett syndrome may also include development of hand stereotypies, such as hand wringing and clapping, and gait abnormalities.8 Most Rett patients typically live into adulthood and require round-the-clock care. 1,9
About DAYBUE® (trofinetide)
Trofinetide is a synthetic analog of the N-terminal tripeptide of insulin-like growth factor 1. The mechanism by which trofinetide exerts therapeutic effects in patients with Rett syndrome is unknown. In animal studies, trofinetide has been shown to increase branching of dendrites and synaptic plasticity signals.10
Important Safety Information for DAYBUE® (trofinetide)
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Warnings and Precautions
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Diarrhea: In a 12-week study and in long-term studies,
85% of patients treated with DAYBUE experienced diarrhea. In those treated with DAYBUE,49% either had persistent diarrhea or recurrence after resolution despite dose interruptions, reductions, or concomitant antidiarrheal therapy. Diarrhea severity was mild or moderate in96% of cases. In the 12-week study, antidiarrheal medication was used in51% of patients treated with DAYBUE.
Advise patients to stop laxatives before starting DAYBUE. If diarrhea occurs, patients should notify their healthcare provider, consider starting antidiarrheal treatment, and monitor hydration status and increase oral fluids, if needed. Interrupt, reduce dose, or discontinue DAYBUE if severe diarrhea occurs or if dehydration is suspected. -
Vomiting: In a 12-week study, vomiting occurred in
29% of patients treated with DAYBUE and in12% of patients who received placebo.
Patients with Rett syndrome are at risk for aspiration and aspiration pneumonia. Aspiration and aspiration pneumonia have been reported following vomiting in patients being treated with DAYBUE. Interrupt, reduce dose, or discontinue DAYBUE if vomiting is severe or occurs despite medical management. -
Weight Loss: In the 12-week study,
12% of patients treated with DAYBUE experienced weight loss of greater than7% from baseline, compared to4% of patients who received placebo. In long-term studies,2.2% of patients discontinued treatment with DAYBUE due to weight loss. Monitor weight and interrupt, reduce dose, or discontinue DAYBUE if significant weight loss occurs.
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Diarrhea: In a 12-week study and in long-term studies,
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Adverse Reactions: The common adverse reactions (≥
5% for DAYBUE-treated patients and at least2% greater than in placebo) reported in the 12-week study were diarrhea (82% vs20% ), vomiting (29% vs12% ), fever (9% vs4% ), seizure (9% vs6% ), anxiety (8% vs1% ), decreased appetite (8% vs2% ), fatigue (8% vs2% ), and nasopharyngitis (5% vs1% ). -
Drug Interactions: Effect of DAYBUE on other Drugs
- DAYBUE is a weak CYP3A4 inhibitor; therefore, plasma concentrations of CYP3A4 substrates may be increased if given concomitantly with DAYBUE. Closely monitor when DAYBUE is used in combination with orally administered CYP3A4 sensitive substrates for which a small change in substrate plasma concentration may lead to serious toxicities.
- Plasma concentrations of OATP1B1 and OATP1B3 substrates may be increased if given concomitantly with DAYBUE. Avoid the concomitant use of DAYBUE with OATP1B1 and OATP1B3 substrates for which a small change in substrate plasma concentration may lead to serious toxicities.
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Use in Specific Population: Renal Impairment
- DAYBUE is not recommended for patients with severe renal impairment.
DAYBUE is available as an oral solution (200 mg/mL).
Please read the accompanying full Prescribing Information, also available at DAYBUE.com
About Acadia Pharmaceuticals
Acadia is advancing breakthroughs in neuroscience to elevate life. Since our founding we have been working at the forefront of healthcare to bring vital solutions to people who need them most. We developed and commercialized the first and only FDA-approved drug to treat hallucinations and delusions associated with Parkinson’s disease psychosis and the first and only approved drug in
References
1 Fu C, Armstrong D, Marsh E, et al. Consensus guidelines on managing Rett syndrome across the lifespan. BMJ Paediatrics Open. 2020; 4:1-14.
2 Kyle SM, Vashi N, Justice MJ. Rett syndrome: a neurological disorder with metabolic components. Open Biol. 2018; 8: 170216.
3 May DM, Neul JL, Satija A, et al. Real-world clinical management of individuals with Rett syndrome: a physician survey. J of Med Econ. 26(1), 1570–1580.
4 Acadia Pharmaceuticals Inc, Data on file. RTT US Prevalence. March 2022.
5 Amir RE, Van den Veyver IB, Wan M, et al. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat Genet. 1999; 23(2): 185-188.
6 Fukuda T, Itoh M, Ichikawa T, et al. Delayed maturation of neuronal architecture and synaptogenesis in cerebral cortex of Mecp2-deficient mice. J Neuropathol Exp Neurol. 2005; 64(6): 537-544.
7 Asaka Y, Jugloff DG, Zhang L, et al. Hippocampal synaptic plasticity is impaired in the Mecp2-null mouse model of Rett syndrome. Neurobiol Dis. 2006; 21(1): 217-227.
8 Neul JL, Kaufmann WE, Glaze DG, et al. Rett syndrome: revised diagnostic criteria and nomenclature. Ann Neurol. 2010; 68(6): 944-950.
9 Tarquinio DC, Hou W, JL Neul et al. The changing face of survival in Rett syndrome and MECP2-related disorders. Pediatr Neurol. 2015; 53(5): 402-411.
10 Acadia Pharmaceuticals Inc., Data on file. Study Report 2566-026. 2010.
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