Daybue’s approval set to make ‘positive impacts’ in Rett syndrome

Acadia Pharmaceuticals' therapy will be available for prescription by end of April

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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The recent U.S. approval of Daybue (trofinetide) as the first treatment for adults and children with Rett syndrome represents a game changer, offering hope for the care of this patient community, say researchers, advocates, and caregivers.

“The availability of a drug that helps with symptoms caused by Rett Syndrome gives us so much hope for a better quality of life for our daughter, Hannah. It also helps to clear a pathway and set the standard for other treatments,” Denay Hooks, whose daughter was diagnosed with Rett in 2013, told Rett Syndrome News

For Acadia Pharmaceuticals, Daybue’s manufacturer, the approval by the U.S. Food and Drug Administration (FDA) was a key milestone, one only made possible by the joint efforts of scientists and the Rett community.

“We share the Rett syndrome community’s excitement,” said Kathie Bishop, PhD, Acadia’s senior vice president, chief scientific officer and head of rare disease. “Over the last few years, we’ve prioritized connecting directly with families in the Rett syndrome community and with representative advocacy groups to make sure we understand the lived experience of this rare disease and the unmet needs of the patient community.

“We are humbled and grateful that our investment in research and development led to the first FDA-approved treatment in this rare condition and hope it sets a powerful example about what can be accomplished to serve the needs of this community and other rare disease communities,” Bishop said.

Daybue will be available by prescription by the end of April, according to Bishop, in line with Acadia’s initial target date.

Hooks has already contacted her daughter’s doctors and hopes to have her on Daybue once it’s available. “After speaking with other parents and reading the results of the clinical trials, we are excited about the possibility that it might improve Hannah’s life,” she said. “Any improvement in her quality of life or independence is a miracle in our book.”

The release of Daybue will be accompanied by a support program from the manufacturer. Called Acadia Connect, it will offer “personal assistance, financial resources, and prescription support to patients and caregivers starting and continuing appropriate Daybue therapy,” Bishop said, who noted the cost of the therapy may vary depending on what type of insurance coverage a family has.

“To fulfill our mission and ensure our promise to patients, we will be working with each family and [healthcare professional] practice to facilitate and/or provide financial assistance to patients regardless of their insurance status,” Bishop said.

More information is available at or by calling 1-844-737-2223, weekdays, from 8 a.m. to 8 p.m. ET.

Hooks said she plans on using it. “We anticipate that there might be difficulties getting our insurance to approve DAYBUE,” Hooks said.  “They are the experts and I am thankful that they are including a program to help families.”

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A positive impact on girls with Rett

Daybue’s active ingredient is an analogue of glypromate, a naturally occurring protein fragment believed to reduce inflammation and promote developing connections between neurons — a process that’s impaired in Rett patients. A liquid solution, the therapy is given by mouth or feeding tube at a dose based on a patient’s weight.

The FDA’s decision to approve Daybue for adults and children 2 and older was mainly supported by data from the Phase 3 LAVENDER trial (NCT04181723), which enrolled 187 girls and young women with Rett syndrome, ages 5-20.

The participants received either Daybue or a placebo for 12 weeks, or about three months. Daybue was administered twice daily, 30 to 60 mL based on body weight.

Results showed patients given Daybue saw an average reduction (improvement) of more than 5 points on the Rett Syndrome Behaviour Questionnaire, a caregiver assessment of Rett symptoms. Those taking a placebo improved by less than 2 points on average.

The best improvements were with fear, anxiety, body rocking, and blank facial expressions.

“The data from the Lavender Phase 3 trials demonstrated a statistically significant and modest improvement in both Rett-associated behaviors … as well as improvements in communication,” said Eric Marsh, MD, PhD, an investigator in the LAVENDER study. “This was important for two reasons. First, over a relatively short time window, changes in behaviors were demonstrated in a relatively large Phase 3 trial in a complex neurodevelopmental disorder, a result which had not been accomplished before. Second, these improvements in their day-to-day activities should make dealing with this devastating disorder a little bit more manageable for the families and caregivers.

The drug will hopefully make everyday activities slightly easier for families.

“Hopefully, with prolonged and persistent improvements in these behavioral domains, functional improvements that can truly impact quality of life will follow,” Marsh said.

Significant gains were also seen in the Clinical Global Impression Scale-Improvement, a clinician-measured tool of disease severity. This means “the clinicians taking care of these individuals, even without knowing if they were on drug or placebo, believed that there were mild or moderate changes in the child,” said Marsh, who’s also a pediatric neurologist at Children’s Hospital of Philadelphia and clinical director of the Orphan Disease Center at University of Pennsylvania.

Social communication skills, such as eye contact and making choices nonverbally, also improved in the Daybue group. This was assessed using the Communication and Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist-Social Composite Score, a measure of communication in infants and toddlers.

Most participants who finished Lavender joined the open-label extension study called LILAC (NCT04279314), wherein all receive Daybue for 40 weeks, or about nine months. Results to date have shown the benefits seen in the parent trial are maintained “and even improving slightly more,” Marsh said. Those who switched from a placebo to Daybue in LILAC are showing the same gains as those who took Daybue in LAVENDER.

The findings support Daybue’s “positive, modest impact on girls with Rett syndrome.”

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Daybue approval ‘offers hope’

The therapy has generally been well tolerated in clinical trials, with diarrhea and vomiting being the most common side effects.

Studies to date have been relatively short, so the long-term impact of the therapy “has the potential to even be more impactful,” Marsh said. “The drug will hopefully make everyday activities slightly easier for families. For example, if the child can stop their hand stereotypies [repetitive movements] while getting dressed or can more consistently make choices with her eyes or hands when eating or during family time, the caregivers will be able to interact more easily and without many of the frustrations that they have day to day.

“These changes, while a typical individual would think are very mild, could have real positive impacts on a family’s [life],” Marsh said.

Hooks agrees. She said she was “devastated” when Hannah was diagnosed and “fearful for her future” because there was no available treatment then. She said parents of those newly diagnosed with the disease can now know Daybue might help reduce the loss of motor, communication, and social skills that characterize Rett. “This exciting news offers hope during a challenging and dark time,” she said.

Another clinical trial, DAFFODIL (NCT04988867), is testing Daybue in 15 girls with Rett syndrome, ages 2-5, a group already eligible for the therapy. Bishop said there’s no reason to believe Daybue’s mechanism of action would work differently for patients older than 20, above the upper age limit for LAVENDER.

Also, because Daybue is believed to enhance the signaling mediated by BDNF, a neuroprotective protein known to promote connections between cells, it might be able to be used in combination with experimental therapies being developed that are targeting mutations in the MECP2 gene, Marsh said.

Bishop said Acadia will continue to invest in rare disease research, including a collaboration with Stoke Therapeutics to develop RNA-based therapies for Rett syndrome and other indications.