Rett Syndrome Clinical Trials

Status: In March 2023, Acadia Pharmaceuticals Inc. announced that their investigational drug, trofinetide, was approved by the U.S. Food and Drug Administration (FDA) for the treatment of Rett syndrome. The FDA’s approval was broad and includes all individuals with Rett syndrome – male and female – aged two and older with no upper limit. The orally administered drug, marketed under the name DAYBUE^™, is commercially available via prescription in the United States. Acadia acquired the global rights to expand access to other countries from Neuren Pharmaceuticals in July 2023. They intend to submit a New Drug Submission (NDS) for trofinetide in Canada by the end of 2024 with plans for Europe, Asia and other regions to be announced at a later date.

To learn more about Acadia Pharmaceuticals, click here.
To learn more about DAYBUE for the treatment of Rett syndrome, click here.
For additional resources, links, and information, click here.
View the Trofinetide Timeline: From Discovery to FDA Approval

Recent News & Updates:
7.13.23 – Acadia Acquires International Rights to Trofinetide
4.17.23 – DAYBUE™ (trofinetide) is Now Available for the Treatment of Rett Syndrome
3.10.23 – DAYBUE™ (trofinetide) Approved by FDA for the Treatment of Rett Syndrome
2.28.23 – LILAC-1 Study Topline Results Announced (Community Letter)
9.12.22 – FDA Grants Priority Review to Trofinetide
7.18.22 – ACADIA Submits NDA for Trofinetide
12.6.21 – Positive Phase 3 LAVENDER Trial Results

Status: In June 2023, Anavex Life Sciences Corp. announced the completion of the EXCELLENCE Phase 2/3 study in girls ages 5-17 with Rett syndrome in Australia, Canada, and the U.K., as well as the Phase 3 adult study in Australia and the U.K. Topline results from both these studies are expected in late 2023. Anavex also announced that adult patients enrolled in its long-term Phase 2 clinical study in the U.S. showed statistically significant reductions in Rett syndrome severity as well as continued improvement from the drug compared to placebo patients as measured by the Rett Syndrome Behavior Questionnaire (RSBQ) over 36 weeks of treatment. The drug has previously received Fast Track designation, Rare Pediatric Disease designation, and Orphan Drug designation from the FDA for the treatment of Rett syndrome. Anavex 2-73 (blarcamesine) is an activator of the sigma-1 receptor and is taken as a liquid once a day.

To learn more about Anavex Life Science, click here.

Recent News & Updates:
6.28.23 – Long-term Clinical Study Demonstrates Disease-Modifying Effects of ANAVEX®2-73 for Rett Syndrome
6.6.23 – Completion of ANAVEX®2-73 (blarcamesine) EXCELLENCE Phase 2/3 Rett Syndrome Clinical Trial
2.1.22 – ANAVEX®2-73 (Blarcamesine) AVATAR Phase 3 Trial met Primary and Secondary Efficacy Endpoints
12.15.20 – Anavex Life Sciences Announces ANAVEX®2-73 Meets Primary and Secondary Endpoints in Clinical Trial
6.5.19 – Anavex Life Sciences Announces First Patient Dosed in Phase 2 Clinical Trial of ANAVEX®2-73

Status: In November 2023, Neurogene Inc. announced the dosing of two pediatric patients in their Phase 1/2 U.S. trial of investigational gene therapy, NGN-401, and that the treatment has been well-tolerated with no treatment-emergent procedure-related serious adverse events (SAEs) or transgene-related overexpression toxicity. This clinical trial will enroll five (5) female patients with Rett syndrome aged 4-10 at clinical trial sites Texas Children’s Hospital, Boston Children’s Hospital, and Children’s Hospital Colorado. The study will follow the patients for five years after dosing, then enroll participants in a long-term observational study for an additional 10 years. The trial is currently recruiting participants.

NGN-401 is a gene replacement therapy delivered by an injection directly into a ventricle in the brain where the AAV-9 virus carries the MECP2 gene to cells in the brain. Pending successful completion of the trial’s upcoming pre-planned independent Data and Safety Monitoring Board review, Neurogene expects to dose a third patient in the first quarter of 2024, report preliminary clinical data from the first patient cohort in Q4 2024 and report data from an expanded number of patients expected in the 2nd half of 2025.

To learn more about Neurogene Inc., click here.
To learn more about enrolling in the Phase 1/2 trial, click here.

Recent News & Updates:
11.30.23 – 1st pediatric patients dosed in U.S. trial of NGN-401
7.18.23 – Neurogene announces merger with Neoleukin Therapeutics (Community Letter)
6.12.23 – Neurogene Announces Locations & Opens Enrollment for US Gene Therapy Clinical Trial
4.18.23 – Update for Rett Syndrome Community and Clarification Concerning Trofinetide
1.23.23 – Neurogene Announces First Rett Syndrome Gene Therapy Trial in U.S.
5.18.22 – Neurogene announces new development program for Rett syndrome, NGN-401 (Letter to Community)

Status: In September 2023, Neurotech International completed recruitment for its Phase I/II clinical trial of NTI164, the company’s medical cannabinoid product being developed as a therapeutic drug for a range of neurological disorders in children including Rett syndrome. The trial will evaluate 14 female participants with Rett syndrome ages 5-18 in Australia.

To learn more about Neurotech International, click here.

Recent News & Updates:
9.26.23 – Neurotech Completes Patient Recruitment in Phase I/II Rett Syndrome Clinical Trial
3.20.23 – Neurotech to Launch Phase II Clinical Trial in Rett Syndrome

Status: In September 2023, Taysha Gene Therapies announced the dosing of the 2nd adult patient in the REVEAL adult Phase 1/2 trial of the investigational gene therapy TSHA-102 after a review by the Independent Data Monitoring Committee (IDMC). Early, interim data from the first patient dosed showed that TSHA-102 was well-tolerated and there were no treatment-emergent serious adverse events (SAEs) reported at the six-week assessment. The first patient also showed clinical improvement in key efficacy measures including the CGI-I and RSBQ at four weeks post-treatment that included autonomic function (sleep and breathing), vocalization, and gross and fine motor skills. They expect to dose the 3rd adult patient and complete enrollment in this low-dose cohort by the end of 2023 which will be evaluated over the next 60+ months. The adult trial is currently recruiting participants in Montreal, Canada, and received approval from Health Canada in November 2023 to expand eligibility criteria adolescent females aged 12 and older. 

TSHA-102 is a gene replacement therapy intended to deliver a functioning copy of MECP2 to the cells in the brain. The injection into the spinal canal includes the AAV-9 virus, which carries the miniMECP2 gene product to the cells for the body to make more MeCP2 protein. The FDA cleared Taysha’s Investigational New Drug (IND) application in the U.S. for the REVEAL pediatric study of females aged 5-8 years old. They expect to dose the first pediatric patient in the 1st quarter of 2024, with plans to expand to ages 3-8 years old in future parts of the study. Taysha has also submitted a Clinical Trial Application (CTA) to the United Kingdom MHRA.

To learn more about Taysha Gene Therapies, click here.
To learn more about enrolling in the REVEAL Adult Phase 1/2 Study, click here.

Recent News & Updates:
11.29.23 – Health Canada authorizes expansion of eligibility to adolescents in REVEAL Phase 1/2 trial
11.14.23 – Early, interim data from the first two adult patients dosed shared in Q3 Financials
9.26.23 – 2nd Adult Patient Dosed & Timeline for U.S. Pediatric Patient Dosing
8.24.23 – U.S. FDA grants Fast Track Designation to TSHA-102
8.14.23 – Positive interim results on 1st patient, US IND cleared, UK CTA submitted, and funding update
7.31.23 – IDMC recommends dosing of 2nd patient (Community Letter)
6.28.23 – Taysha encouraged by initial clinical observations of 1st adult patient dosed
6.5.23 – First adult patient dosed with TSHA-102
2.1.23 – TSHA-102 Expansion Update
11.17.22 – Taysha updates Rett syndrome community on gene therapy clinical trial (VIDEO)
10.24.22 – Taysha and Astellas announce strategic investment (Community Letter)
3.29.22 – Taysha announces initiation of clinical development of TSHA-102 in Rett syndrome

ACTX-101 is an AAV9-delivered X-reactivation gene therapy for the treatment of Rett syndrome. In May 2022, Alcyone presented preclinical data showing ACTX-101 safely and effectively reactivates the inactive X chromosome in a Rett syndrome mouse model and is safe in a preliminary nonhuman primate study.

To learn more about Alcyone Therapeutics, click here.

More News & Updates from Alcyone Therapeutics: 
5.18.22 – Alcyone Presents Preclinical Data on Gene Therapy Programs

AMO-4 is a glutamate modulator that has shown significant promise as a potential treatment for Rett syndrome based on extensive drug discovery screen in a mouse model completed through IRSF’s Scout Program. In June 2018, the U.S. FDA granted Orphan Drug Designation to AMO-04 for the treatment of Rett syndrome.

To learn more about AMO Pharma, click here.

More News & Updates from AMP Pharma:
6.13.18 – AMO Pharma Receives FDA Orphan Drug Designation for AMO-04 in Treatment of Rett Syndrome
AMO-04 – Rettsyndrome.org Q&A

KIT-13, a synthetic derivative of plasmalogen, a type of phospholipid that is present in the membranes of cells throughout the body including the brain. It has shown strong anti-inflammatory effects by inhibiting the nuclear accumulation of p65, suppressing the expression of IL-1?, and inducing phosphorylation of ERK, suggesting promise for treating Rett syndrome. KIT-13 was granted Rare Pediatric Disease Designation and Orphan Drug Designation from the U.S. FDA in March 2023.

To learn more about NeuroCores, click here.

NLX-101 is a novel compound that activates serotonin 5-HT1A receptors. The administration of NLX-101 in Rett mice reduced the occurrence of apneas and normalized the irregular breathing patterns without interfering with other behaviors, suggesting that NLX-101 may represent a promising strategy for treating breathing disturbances in Rett syndrome.

To learn more about Neurolixis, click here.

More News & Updates from Neurolixis Inc.:
3.3.2014 – European Commission approves Orphan Medicinal Product designation for NLX-101

RVL001 is a small molecule oral therapeutic identified by Unravel’s proprietary drug prediction platform as potentially beneficial for patients with Rett Syndrome.

To learn more about Unravel Biosciences Inc., click here.

More News & Updates:
2.15.2023 – Unravel Biosciences announces positive feedback from FDA pre-IND Meeting on RVL001 Rett Syndrome Program

DepYmed is developing novel therapeutics targeting the role of protein tyrosine phosphatases in signaling pathways involved in the pathology of multiple diseases including Rett syndrome.

To learn more about DepYmed, click here.

Herophilus is a neurotherapeutics startup using robotic automation to “industrialize” the organoid and scale up use of the next-generation human in vitro models in drug discovery experiments for brain diseases. Its lead drug candidate is the first small molecule therapy for Rett Syndrome with the potential to reverse the root cause of the disease, MECP2 deficiency.

To learn more about Herophilus, click here.

Lucy Therapeutics develops therapies based on mitochondrial small-molecule treatments and biomarkers for neurological diseases.

To learn more about Lucy Therapeutics, click here.

More News & Updates:
10.11.23 – Lucy Therapeutics Expands Cutting-Edge Medical Research Program with Grant from IRSF

Prilenia is continuing preclinical evaluation of pridopidine, a sigma-1 receptor (S1R) agonist with neuroprotective properties administered orally twice daily, for the treatment of Rett syndrome. It is currently in late-stage development and clinical trials for the treatment of Huntington’s disease and ALS.

To learn more about Prilenia, click here.

Shape Therapeutics is a biopharmaceutical company using RNA technologies to correct genetic mutations.

To learn more about Shape Therapeutics, click here.

Stoke Therapeutics Pipeline
Stoke Therapeutics and Acadia Pharmaceuticals Collaborate to Pursue RNA Treatment – 1.10.22

Novartis Update 2.8.21
Novartis Update 9.02.20
Avexis Update 8.20.20
Avexis Update 8.22.19

For more information, visit Novartis Gene Therapies.

5.4.20 Newron Reports Top-Line Results from its STARS Study
4.12.19 Newron Thank You

For more information, visit Newron Pharmaceuticals.

Trial Closure Announcement 11.12.20
Trial Criteria_9.6.19
GW Research May, 2019

For more information, visit GW Pharmaceuticals.