IRSF Blog

October 29, 2024

DAYBUE in the Real World

Answers to your most frequently asked questions and resources to find out more about the first-ever FDA-approved treatment of Rett syndrome.

According to the National Organization for Rare Disorders (NORD), less than 5% of the more than 10,000 known rare diseases have an FDA-approved treatment; as of last year, Rett syndrome became one of them. In March 2023, the U.S. Food and Drug Administration (FDA) approved trofinetide for the treatment of Rett syndrome, a huge milestone for our Rett community. Now marketed under the name DAYBUE™ by Acadia Pharmaceuticals, the drug has been commercially available via prescription in the United States for over a year, giving our community more insight into real-world usage, benefits, and side effects.

With Acadia’s recent announcement that DAYBUE received approval to expand into Canada, we want to make sure you have all the facts about the treatment and the resources to learn more. Below you’ll find answers to some of the questions we receive most frequently about the treatment.

*Please Note: The information below is intended for informational purposes only and is not intended to serve as a substitute for the consultation, diagnosis, and/or medical treatment of a qualified physician or healthcare provider. Always seek the advice of your physician or healthcare provider with any questions about your specific medical condition.


DAYBUE official logo

What is DAYBUE™ (trofinetide) and how is it administered?
DAYBUE is a prescription, oral medication taken twice daily with or without food. It is a strawberry-flavored liquid that can be swallowed or given through a G-tube. The amount of DAYBUE taken is determined by the weight of the individual with Rett syndrome. (Source)

Who is DAYBUE approved for?
DAYBUE is approved for use in the United States and Canada. In the U.S., DAYBUE was approved in March 2023 and is currently commercially available. It is indicated for the treatment of Rett syndrome in adults and pediatric patients 2 years of age and older with no upper limit. (Source) In Canada, DAYBUE was approved by Health Canada in October 2024 and will be commercially available soon. It is indicated for the treatment of Rett syndrome in adults and pediatric patients 2 years of age and older and weighing at least 9 kg. (Source)

Acadia acquired global rights to expand access to trofinetide to additional countries from Neuren Pharmaceuticals in July 2023. (Source)

How many individuals with Rett are taking DAYBUE?
As of October 2024, over 1,500 individuals in the U.S. have started treatment with DAYBUE according to Acadia. This includes a diverse group of patients ranging in age from 2 to 67 years, with about 25% being over the age of 21. Approximately 70% of those who start DAYBUE have continued treatment for at least six months. (Source)

How was DAYBUE (trofinetide) studied?
DAYBUE has been studied for nearly two decades. Trofinetide was initially investigated in traumatic brain injury by Neuren Pharmaceuticals in the early 2000s. IRSF’s then-CSO, Dr. Steve Kaminsky, helped identify the potential of trofinetide for Rett patients, and IRSF funded Neuren’s phase 2 clinical trials of trofinetide in individuals with Rett. After positive results were reported, Acadia Pharmaceuticals acquired the rights to trofinetide in North America and executed the phase 3 clinical trial program. (Source)

The FDA approval for patients 5 years of age and older is informed by the results of the LAVENDER™ clinical trial, a randomized phase 3 study that evaluated the effectiveness and safety of DAYBUE in 187 female patients with Rett syndrome aged 5 to 20 across 12 weeks. Half of the patients were given DAYBUE and half a placebo. Data from DAFFODIL™, an open-label phase 2/3 study of female patients aged 2-4, informed the approval for pediatric patients.

154 of the LAVENDER patients continued into a 40-week open-label extension safety study called LILAC™ where all patients were given DAYBUE and 77 patients then enrolled in the 32-month LILAC-2™.  Additionally, there is an ongoing phase 4 study called LOTUS™ evaluating patients prescribed DAYBUE over the first 12 months on the drug.

How was the effectiveness of DAYBUE measured?
In the LAVENDER study, caregivers used the RSBQ and doctors used the CGI-I scale to evaluate patients on DAYBUE versus placebo. (Source)

Caregivers evaluated changes in 45 items using the Rett Syndrome Behaviour Questionnaire (RSBQ) which includes symptoms like breathing, hand movements, and repetitive behaviors. Caregivers score each item as not true (0), somewhat/sometimes true (1), or very/often true (2). Added together, these scores determine the RSBQ total score across symptoms, and researchers looked for statistically significant changes in the average RSBQ total score from the start of the trial.

Doctors used the Clinical Global Impression-Improvement (CGI-I) scale to evaluate the improvement or worsening of symptoms.

What did the studies find?
Over the course of the 12-week LAVENDER study, both doctors and caregivers observed significant improvements in the signs and symptoms of Rett syndrome. Doctors observed that 38% of patients had improvements in symptoms with DAYBUE versus 15% of patients on placebo.

On the RSBQ—where a lower score means less severe symptoms—caregivers reported that patients receiving DAYBUE saw a decrease of 4.9 in average RSBQ total score versus 1.7 for the placebo group. In those that continued to LILAC, the improvement from baseline was -7.3 for those treated with trofinetide in LAVENDER at week 40, showing that treatment continued to improve symptoms. By LILAC-2 concluding at week 104, the RSBQ improvement from baseline was -11.8. It is important to note that not all patients in the clinical trial responded to treatment and the participants were also receiving other types of therapy, like physical, occupational, or speech therapy.

What do these numbers and scales mean in terms of real-world benefits?
Because each individual with Rett syndrome is unique with unique symptoms, improvements in the studies were different for everyone. At daybue.com, you can find caregiver descriptions of the improvements observed in the LAVENDER study and stories about their experience both during the studies and in real life.

Additionally, the ongoing LOTUS phase 4 study is providing further insights into DAYBUE’s effects in real-world scenarios. In a presentation of six-month interim data from 101 participants aged 2 to 60 years, Acadia shared that the caregivers of more than two-thirds of participants reported experiencing improvements in at least one area within the first month of treatment. Over six months, the most consistently observed benefits were in nonverbal communication (reported by 58.5% of caregivers), alertness (51.2%), and social interaction (40.2%).

What are the possible side effects?
Diarrhea is a common side effect of DAYBUE that can sometimes be severe, and other notable side effects include vomiting and weight loss. In LAVENDER, 82% of patients on DAYBUE reported diarrhea versus 20% on placebo and 29% reported vomiting compared to 12% on placebo.

In the LILAC-1 and LILAC-2 studies, the 40-week and 32-month extensions, common adverse events included diarrhea (reported by 74.7% and 53.2% of participants, respectively) and vomiting (reported by 28.6% and 19.5%). Most of these adverse events were mild to moderate, but they did lead to treatment discontinuation for some participants. (Source)

Are there ways to manage these side effects?
Participants in the studies were required to closely follow study protocol including starting at the recommended weight-based dose and continuing treatment for the duration of the study. Since these studies, Acadia and healthcare providers, including directors from our Center of Excellence network, have developed strategies and published papers on managing these side effects in a real-world setting. Your doctor might recommend stopping the use of laxatives or stool softeners, adding supplemental fiber to your child’s diet, or starting with a lower dose of DAYBUE and increasing to the FDA-approved dose over time. (Source)

A bottle of DAYBUE

How does DAYBUE work?
Daybue (trofinetide) is a novel synthetic analog of the amino-terminal tripeptide of IGF-1 designed to treat the core symptoms of Rett syndrome by potentially reducing neuroinflammation and supporting synaptic function. However, the exact mechanism by which it exerts therapeutic effects in patients with Rett is unknown. (Source)

Who can prescribe DAYBUE?
Any healthcare provider can prescribe DAYBUE. Information exclusively for prescribers can be found on DAYBUE’s official HCP website.

Can I get DAYBUE at my local pharmacy?
No, DAYBUE comes from a specialty pharmacy, AnovoRx, because it has special handling, storage, and delivery requirements. AnovoRx will process and fill your prescription and ship you a refrigerated box each month. (Source)

How much does DAYBUE cost?
While there is a list price for DAYBUE, this is not the cost that patients pay. Eligible patients with commercial insurance may pay as little as $0 per month. If you don’t have insurance or DAYBUE is not covered by your insurance plan, Acadia currently offers financial assistance options. Once DAYBUE is prescribed by your doctor, Acadia Connect® helps patients navigate insurance and obtain coverage. (Source)

Will taking DAYBUE impact participation in future clinical trials?
The use of DAYBUE does not currently exclude individuals from participation in most ongoing clinical trials, including those focused on gene therapy, although some specific trials may require discontinuation of DAYBUE before enrollment. (Source)

How can I learn more about DAYBUE?
Parents and caregivers can find more information about DAYBUE at daybue.com. Acadia also offers Acadia Connect, a patient and family support program that connects families with educational support and resources throughout the DAYBUE treatment journey. They also host Discovering DAYBUE™, a series of in-person and virtual educational sessions.

Always consult your doctor or neurologist about additions or changes to your treatment plan. DAYBUE will not be right for every individual with Rett.

HCPs should visit daybuehcp.com for prescribing information, the safety profile, and documents to help patients get started.


IRSF is with you every step of the way. Email us directly at treatment@rettsyndrome.org and we will do everything we can to answer your questions or direct you to the resources you need. To learn more about DAYBUE, please visit daybue.com or reach out to one of our 21 IRSF-designated Rett syndrome Center of Excellence clinics.

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