Daybue up for review in Canada as country’s 1st Rett therapy

The prioritized application follows last year's trial-supported approval in the US

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Health Canada has agreed to review Acadia Pharmaceuticals’ application seeking approval of trofinetide — sold in the U.S. as Daybue — for the treatment of Rett syndrome.

The regulatory body granted the application priority review, which is reserved for submissions that address an unmet need or offer benefits over existing therapies for serious, life-threatening, or severely debilitating diseases.

“Rett syndrome is a profoundly debilitating and complex neurodevelopmental disorder that presents differently across patients and can lead to an array of unpredictable symptoms,” Pamela di Cenzo, vice president and general manager of Acadia in Canada, said in a company press release. “If granted marketing authorization, trofinetide will be the first option available to treat Rett syndrome in Canada.”

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Daybue is a liquid solution containing an analogue of glypromate, a protein fragment found naturally in the brain that’s believed to ease inflammation and promote the development of nerve cell connections that are impaired in Rett syndrome.

It was approved in the U.S. a little over a year ago for Rett patients ages 2 and older, making it the first therapy to be approved for the rare neurodevelopmental disease in the country.

Health Canada’s decision to now review the therapy as possibly the first treatment for Rett in that region has been met with enthusiasm from the Rett community, including the Ontario Rett Syndrome Association (ORSA).

“O.R.S.A. is pleased that Health Canada has granted Priority Review for this promising treatment which, if approved, would be a significant step forward in addressing the unmet medical needs of Canadians living with Rett syndrome,” said Sabrina Millson, ORSA’s president.

“Our community of patients, caregivers and supporters are excited at the prospect of having a treatment option for Rett syndrome,” Millson added.

The therapy’s development

Acadia licensed the North American rights to the therapy from developer Neuren Pharmaceuticals in 2018, expanding the agreement beyond that region last year. Acadia has indicated plans to seek similar approvals of trofinetide in Europe, Asia, and other regions.

Daybue’s benefits in Rett were demonstrated in the Phase 3 LAVENDER clinical trial (NCT04181723), which involved 187 girls and young women with Rett syndrome, ages 5 to 20. Participants were randomly assigned to receive Daybue — taken orally or via feeding tube — or a placebo twice daily for about three months.

Results showed the treatment was superior to the placebo for improving caregiver- and clinician-rated measures of neurobehavioral symptom severity, meeting the trial’s main goals. It also outperformed the placebo in improving measures of communication, meeting a key secondary goal.

Most participants who completed LAVENDER continued to receive Daybue in a 40-week open-label extension trial called LILAC (NCT04279314) and could then further continue long-term treatment for up to 32 months — more than 2.5 years — in the LILAC-2 extension study (NCT04776746).

Findings from LILAC-2 showed that long-term treatment was well-tolerated and led to sustained reductions in Rett-associated symptoms.

Another Acadia-sponsored Phase 2/3 open-label study, DAFFODIL (NCT04988867), tested Daybue’s safety and tolerability in 15 girls, ages 2-5, with Rett syndrome. Twelve girls completed the trial, which was stopped early once Daybue was approved in the U.S.

Final results, presented at a recent scientific conference, showed that the therapy had an acceptable safety and pharmacological profile with up to about 1.5 years of treatment in these young patients.

Exploratory efficacy measures showed that, as in LAVENDER, Daybue was associated with caregiver- and clinician-reported improvements in life quality and Rett symptoms.

In exit interviews following the open-label LILAC-2 and DAFFODIL studies, caregivers generally reported meaningful improvements with Daybue treatment, particularly in terms of hand use, engagement with others, eye gaze, focusing, acquisition of new words, and use of eye-gaze devices.

Nearly all interviewed caregivers reported being satisfied or very satisfied with the therapy.