Long-term Daybue led to continual improvements in patients: Studies
'Meaningful improvements' in physical, social functioning noted by caregivers
Long-term treatment with Daybue (trofinetide) led to continual improvements among children and young adults with Rett syndrome in extension studies, with patients experiencing notable benefits in communication and other relevant issues, according to new data.
Slightly more than a year ago, Daybue became the first treatment for Rett syndrome to be approved by the U.S. Food and Drug Administration. That approval was based mainly on positive data from a Phase 3 clinical trial called LAVENDER (NCT04181723), in which more than 180 female Rett patients ages 5 to 20 were given Daybue or a placebo for about three months.
After LAVENDER ended, 154 of the patients continued into an extension study called LILAC-1 (NCT04279314), in which all were treated with Daybue for 40 weeks (meaning about one year of total treatment for those who’d received Daybue in LAVENDER). Then, 77 of the patients continued to another extension study, LILAC-2 (NCT04776746), where all were given Daybue for another 32 months (nearly three years).
Full results from these two extension trials were recently published in Med, in a pair of papers: “Trofinetide for the treatment of Rett syndrome: Results from the open-label extension LILAC study,” and “Trofinetide for the treatment of Rett syndrome: Long-term safety and efficacy results of the 32-month, open-label LILAC-2 study.” Both studies were sponsored by Acadia Pharmaceuticals, the company that sells Daybue.
“These publications add to the growing body of research on clinical experience with Daybue and its potential ongoing impact for those living with this condition,” Alan Percy, MD, a professor at The University of Alabama at Birmingham and lead author of both papers, said in a press release from Acadia. The new data “provide deeper insight into the long-term safety and potential benefit of Daybue for patients with Rett syndrome.”
Diarrhea most common side effect of Daybue
Safety data from the LILAC studies didn’t reveal any unexpected surprises. The most common side effect of Daybue was diarrhea, followed by vomiting, both of which are well-documented side effects of the therapy. However, quite a few patients chose to discontinue treatment due to the side effects. In LILAC-1, more than 1 in 5 (21.4%) of the participants quit the study early because of diarrhea, and another 6.5% discontinued because of vomiting. Four deaths that occurred during LILAC-2 were considered not related to Daybue.
To measure the efficacy of Daybue, both LILAC trials used the same main measures that were employed during the LAVENDER study: a caregiver-rated assessment of Rett symptoms called the Rett Syndrome Behaviour Questionnaire (RSBQ), and a clinician-rated test of overall health called the Clinical Global Impression Scale-Improvement (CGI-I).
In the three-month LAVENDER study, patients given Daybue experienced a mean improvement of 5.2 points on the RSBQ. Long-term data from the LILAC studies showed these improvements continued with long-term treatment. Mean RSBQ scores improved by 7.3 points by the end of LILAC-1 in patients who’d been on Daybue in LAVENDER, compared with scores before they starting that original trial.
Patients who switched from the placebo in LAVENDER to Daybue in LILAC-1 experienced similar improvements after starting on active therapy, with mean RSBQ scores improving by 7 points at the end of the study.
The improvements continued with long-term Daybue treatment in LILAC-2. By the end of that study, mean RSBQ scores had improved by 9.8 points among patients given Daybue in LAVENDER, and by 13.8 points in those who got the placebo in the original trial. After 102 weeks (roughly two years) on Daybue, more than 4 in 5 (81.8%) patients had RSBQ improvements of at least 10%.
The extent of RSBQ score improvement was similar regardless of patient factors such as age and type of Rett-causing mutation. All subscores of the RSBQ tended to improve with Daybue.
Clinician-rated test showed same trend as caregiver assessment
The clinician-measured CGI-I showed the same trend as RSBQ scores, with average scores continuously improving with long-term Daybue treatment irrespective of factors such as patient age and mutation type. Collectively, the data suggest Daybue led to “meaningful improvements in patient communication, engagement, and ability to move independently, without new safety concerns,” the researchers wrote.
At the end of LILAC-2, 27 caregivers of children who completed the study took part in interviews to discuss their experiences. More than 40% of these caregivers said their child was having an easier time engaging with others and/or using their hands, and more than 30% reported more normative eye gaze. Inability to communicate, which was reported as the issue with the most impact on these children, was where caregivers said the most important improvements were observed.
More than half of the caregivers said their own lives were noticeably improved because their child was having an easier time of things.
“Consistent with the quantitative improvements in [Rett] symptoms observed, qualitative caregiver interviews highlighted a wide range of meaningful improvements in their child’s physical and social functioning,” the researchers wrote.
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