FDA Grants Rare Pediatric Disease Designation to Trofinetide for Rett Syndrome

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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The U.S. Food and Drug Administration (FDA) granted rare pediatric disease designation to trofinetide, a potential oral therapy for people with Rett syndrome.

The designation provides priority review to investigational treatments with potential to provide clinically meaningful benefits in serious or life-threatening rare diseases mainly affecting individuals younger than 18.

If the FDA ultimately approves trofinetide, Acadia Pharmaceuticals — which holds an exclusive license from Neuren Pharmaceuticals to develop and market trofinetide in North America — may quality for a voucher redeemable for priority review of a new drug application for a different product.

The voucher program aims to boost treatment development for rare pediatric diseases that might otherwise not be profitable. Under the companies’ license agreement, Neuren will be eligible to receive one-third of the market value of any priority review voucher associated with trofinetide’s FDA approval.

“We are pleased that the FDA has recognized the unmet need currently experienced by Rett patients and their families, and our goal is to bring a treatment option forward as soon as possible,” Serge Stankovic, MD, Acadia’s president, said in a press release.

Trofinetide, previously known as NNZ-2566, is a modified version of glypromate (GPE), a product of insulin-like growth factor 1 (IGF-1) breakdown in the brain. Both proteins are important for normal functioning of the developing brain, and for responding to disease, stress, and injury in the mature brain.

Trofinetide was designed to mimic GPE’s biological functions while having better pharmacological properties: easier storage, oral administration, and longer periods in the bloodstream.

Some studies have reported the presence of abnormally low brain levels of IGF-1 in several conditions, including Rett syndrome, fragile X syndrome, and brain injury. Restoring the levels of IGF-1 and GPE may help prevent further brain damage in people with these disorders.

Results from a previous Neuren-sponsored Phase 2 trial (NCT02715115) in 82 girls ages 5 to 15 with Rett syndrome revealed that the highest dose tested (200 mg/kg) was safe and significantly eased a range of Rett’s core symptoms, compared with a placebo.

Acadia launched the Phase 3 LAVENDER clinical trial (NCT04181723) to evaluate trofinetide’s safety and effectiveness in up to 184 girls and young women ages 5 to 20 with Rett syndrome.

Participants, currently being recruited at 13 clinical sites across the U.S., will be randomly assigned to receive either an oral solution of trofinetide or a placebo for 12 weeks, after which they will be followed for 30 more days for safety measurements.

Trofinetide’s effectiveness in lessening Rett patients’ neurobehavioral symptoms will be assessed by caregivers using the Rett Syndrome Behaviour Questionnaire and by clinicians using the Clinical Global Impression Scale-Improvement. Results are expected by 2021.

All participants who complete LAVENDER will have the opportunity to enter an extension study called LILAC, in which all patients will receive trofinetide for nine months. After completing LILAC, eligible patients may continue treatment in a second extension trial, LILAC-2.

More information about the LAVENDER and LILAC studies, including eligibility criteria, can be found here.

LAVENDER and both extension trials are expected to provide clinical data on the long-term tolerability, safety, and effectiveness of trofinetide in Rett syndrome. If positive, the results are meant to be included in a new drug application seeking trofinetide’s approval in the U.S.

Stankovic said that FDA’s rare pediatric disease designation for trofinetide is “an encouraging step forward.”

Trofinetide has also received orphan drug designation from both the FDA and the European Medicines Agency, and fast track designation from the FDA as a potential treatment for Rett syndrome.

These designations are meant to speed up the therapy’s development and review, as well as to provide regulatory support, financial benefits, and marketing exclusivity for a period of time upon approval (seven years in the U.S. and 10 years in Europe).

Neuren is also exploring the therapy’s potential in fragile X syndrome, the most frequent genetic cause of autism. The FDA granted the treatment fast track status and orphan drug designation for this indication.