What is DAYBUE™ and how was it studied?
Kate, age 9,
living with
Rett syndrome,
with her caregivers
DAYBUE is the first and only treatment approved by the FDA specifically indicated for RTT in adults and pediatric patients 2 years of age and older.1,2
Trofinetide is a synthetic analog of a naturally occurring molecule known as the tripeptide glycine-proline-glutamate (GPE), a cleavage product of insulin-like growth factor-1 (IGF-1).3
The mechanism by which trofinetide exerts therapeutic effects in patients with RTT is unknown.1
DAYBUE was evaluated in a pivotal Phase 3 trial of 187 patients with RTT 1,4
LAVENDER™ (NCT04181723)5 was a 12-week, randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy and safety of DAYBUE.1,4 Following LAVENDER, patients could enter an open-label extension (OLE) study for up to 40 weeks.4
aPatients were stratified by age (5-10, 11-15, and 16-20 years) and baseline Rett Syndrome Behaviour Questionnaire (RSBQ) severity (total score of <35 and ≥35) and randomized 1:1 to trofinetide or placebo groups.6
At baseline, participants exhibited a range of clinical characteristics, disease severity, and comorbidities6
In an open-label study in pediatric patients 2 to 4 years of age with RTT, a total of 13 patients received DAYBUE for at least 12 weeks, and 9 patients received DAYBUE for at least 6 months1
Both caregivers and clinicians evaluated the efficacy of DAYBUE1
RTT caregivers evaluated changes in a range of symptoms using the RSBQ1
The Rett Syndrome Behaviour Questionnaire (RSBQ) is a caregiver-completed measurement scale used in RTT studies.9,11,12 This validated scale is used to assess 45 common symptoms of RTT, asking caregivers to rate each item as it relates to their child.9
Items in the RSBQ include a range of symptoms, such as1,9:
Breathing
Hand movements or stereotypies
Repetitive behaviors
Nighttime behaviors
Vocalizations
Facial expressions
Eye gaze
Mood
RSBQ scoring
Using the RSBQ, caregivers assess RTT symptoms using a 0- to 2-point scale where 0 is “not true,” 1 is “somewhat or sometimes true,” and 2 is “very true or often true”1,9
The sum score of all 45 items equals the RSBQ total score. The maximum possible score is 901,9
A lower score reflects lesser severity in signs and symptoms of Rett syndrome1
As an example, the table below shows the scoring for a single item assessed in the RSBQ9:
Important Safety Information and Indication
Warnings and Precautions
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 of mild or moderate severity in 96% of cases. In the 12-week study, antidiarrheal medication was used in 51% of patients treated with DAYBUE.
Patients should stop taking 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.
Weight Loss: In the 12-week study, 12% of patients treated with DAYBUE experienced weight loss of greater than 7% from baseline, compared to 4% 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.
Adverse Reactions: The common adverse reactions (≥5% for DAYBUE-treated patients and at least 2% greater than in placebo) reported in the 12-week study were diarrhea (82% vs 20%), vomiting (29% vs 12%), fever (9% vs 4%), seizure (9% vs 6%), anxiety (8% vs 1%), decreased appetite (8% vs 2%), fatigue (8% vs 2%), and nasopharyngitis (5% vs 1%).
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.
Use in Specific Population: Renal Impairment
DAYBUE is not recommended for patients with moderate or severe renal impairment.
DAYBUE is available as an oral solution (200mg/mL).
Indication
DAYBUE is indicated for the treatment of Rett syndrome in adults and pediatric patients 2 years of age and older.
Please read the full Prescribing Information.
Important Safety Information and Indication
Warnings and Precautions
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 of mild or moderate severity in 96% of cases. In the 12-week study, antidiarrheal medication was used in 51% of patients treated with DAYBUE.
Patients should stop taking 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.
Weight Loss: In the 12-week study, 12% of patients treated with DAYBUE experienced weight loss of greater than 7% from baseline, compared to 4% 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.
Adverse Reactions: The common adverse reactions (≥5% for DAYBUE-treated patients and at least 2% greater than in placebo) reported in the 12-week study were diarrhea (82% vs 20%), vomiting (29% vs 12%), fever (9% vs 4%), seizure (9% vs 6%), anxiety (8% vs 1%), decreased appetite (8% vs 2%), fatigue (8% vs 2%), and nasopharyngitis (5% vs 1%).
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.
Use in Specific Population: Renal Impairment
DAYBUE is not recommended for patients with moderate or severe renal impairment.
DAYBUE is available as an oral solution (200mg/mL).
Indication
DAYBUE is indicated for the treatment of Rett syndrome in adults and pediatric patients 2 years of age and older.
Please read the full Prescribing Information.
References: 1. Acadia Pharmaceuticals Inc. DAYBUE [Package Insert]. San Diego, CA, 2023. 2. Acadia Pharmaceuticals announces U.S. FDA approval of DAYBUE™ (trofinetide) for the treatment of Rett syndrome in adult and pediatric patients two years of age and older. [press release]. Acadia Pharmaceuticals Inc. March 10, 2023. 3. Neul JL, Glaze DG, Percy AK, et al. Improving treatment trial outcomes for Rett syndrome: the development of Rett-specific anchors for the Clinical Global Impression Scale. J Child Neurol. 2015;30(13):1743-1748. 4. Neul JL, Percy AK, Benke TA, et al. Design and outcome measures of LAVENDER, a phase 3 study of trofinetide for Rett syndrome. Contemp Clin Trials. 2022;114:106704. 5. Study of trofinetide for the treatment of girls and women with Rett syndrome (LAVENDER™). ClinicalTrials.gov identifier: NCT04181723. Accessed June 15, 2023. https://clinicaltrials.gov/ct2/show/NCT04181723 6. Neul JL, Percy AK, Benke TA et al. Trofinetide for the treatment of Rett syndrome: a randomized phase 3 study. Nat Med (2023). 7. Open-label extension study of trofinetide for the treatment of girls and women with Rett syndrome (LILAC™). ClinicalTrials.gov identifier: NCT04279314. Accessed March 10, 2023. https://clinicaltrials.gov/ct2/show/NCT04279314. 8. Acadia Pharmaceuticals Inc. Data on file. ACP- 2566-004. September 2022. 9. Mount RH, Charman T, Hastings RP, et al. The Rett Syndrome Behaviour Questionnaire (RSBQ): refining the behavioural phenotype of Rett syndrome. J Child Psychol Psyc. 2002;43(8):1099-1110. 10. Guy W. ECDEU Assessment Manual for Psychopharmacology, Revised, 1976. US Department of Health, Education, and Welfare. DHEW Publication No. (ADM) 76-338. Accessed January 19, 2023. https://archive.org/details/ecdeuassessmentm1933 guyw/mode/1up?ref=ol&view=theater 11. O’Leary HM, Kaufmann WE, Barnes KV, et al. Placebo-controlled crossover assessment of mecasermin for the treatment of Rett syndrome. Ann Clin Transl Neurol. 2018;5(3):323-332. 12. Khwaja OS, Ho E, Barnes KV, et al. Safety, pharmacokinetics, and preliminary assessment of efficacy of mecasermin (recombinant human IGF-1) for the treatment of Rett syndrome. Proc Natl Acad Sci USA. 2014;111(12):4596-4601. 13. Glaze DG, Neul JL, Kaufmann WE, et al. Double-blind, randomized, placebo-controlled study of trofinetide in pediatric Rett syndrome. Neurology. 2019;92(16):e1912-e1925.
Welcome to the DAYBUE™ (trofinetide) website.
This information is intended for US healthcare professionals only.
Using the RSBQ, caregivers were asked to score 45 symptoms of RTT on a scale from 0 (not true) to 2 (very/often true) .1
The rating scale and items in the RSBQ are shown below.9
Hand movements are uniform and monotonous
Has difficulty in breaking/stopping hand stereotypies
There are times when breathing is deep and fast (hyperventilation)
There are times when breath is held
The amount of time spent looking at objects is longer than the time spent holding or manipulating them
Makes mouth grimaces
There are times when parts of the body are held rigid
Restricted repertoire of hand movements
Has wounds on hands as a result of repetitive hand movements
Makes grimacing expressions with face
Swallows air
Does not use hands for purposeful grasping
Tendency to bring hands together in front of chin or chest
Air or saliva is expelled from mouth with force
Seems frightened when there are sudden changes in own body position
Spells of laughter for no apparent reason during the day
Grinds teeth
Uses eye gaze to convey feelings, needs, and wishes
Shifts gaze with a slow horizontal turn of head
Spells of inconsolable crying for no apparent reason during the day
Spells of laughter for no apparent reason during the night
Spells of apparent panic
Has frequent naps during the day
Spells of screaming for no apparent reason during the day
Makes repetitive hand movements with hands apart
Screams hysterically for long periods of time and cannot be consoled
Spells of screaming for no apparent reason during the night
Vocalizes for no apparent reason
Rocks self when hands are prevented from moving
There are times when she appears miserable for no apparent reason
Abrupt changes in mood
Spells of inconsolable crying for no apparent reason during the night
Makes repetitive movements involving fingers around tongue
Rocks body repeatedly
Appears isolated
Vacant “staring” spells
Abdomen fills with air and sometimes feels hard
There are certain periods where she performs much worse than usual
There are times when she is irritable for no apparent reason
Seems to look through people into the distance
Although can stand independently tends to lean on objects or people
Expressionless face
Spells of apparent anxiety/fear in unfamiliar situations
Makes repetitive tongue movements
Walks with stiff legs
Select inclusion criteria6
Female subjects 5 to 20 years of age
Body weight ≥12 kg at screening
Could swallow the study medication provided as a liquid solution or could take it by gastrostomy tube
Had classic/typical RTT
Had a documented disease-causing mutation in the MECP2 gene
Had a stable pattern of seizures, or had no seizures within 8 weeks of screening