Clinical Trial News & Updates
The most up-to-date information on clinical research to deliver treatments and cures for Rett.
More than 20 companies are currently working on treatments that will bring us even closer to a world without Rett syndrome. Fifteen years ago, there were none. Scroll down to learn more about the companies investing in Rett syndrome studies, the promising compounds being tested, and the most up-to-date status on their progress. For questions, please email us.
rett CLINICAL programs PIPELINE
Click the image below for an overview of all companies actively investing in Rett syndrome treatments. For more detailed information about each company’s progress, scroll down.
Stages of clinical development
The therapy development path is divided into five stages. To learn more about the research and treatment development process, visit our Rett Research Ready resource.
development and clinical trial status
Learn more about the companies investing in Rett syndrome below and the status of their development.
STAGE 5: REGULATORY APPROVAL & POST-MARKET SAFETY MONITORING
The following companies have successfully completed clinical trials and received regulatory approval for a Rett syndrome treatment.
Status: In March 2023, Acadia Pharmaceuticals Inc. announced that the U.S. Food and Drug Administration (FDA) approved their investigational drug, trofinetide, 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. (en español, haga clic aquí)
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
STAGE 4: DRUG REVIEW
The following companies have applied to a regulatory agency like the FDA for permission to market a treatment after clinical trial results indicated the treatment is safe and effective. This stage may take 1-2 years once an NDA is submitted.
STAGE 3: ACTIVE CLINICAL TRIALS & RESEARCH
The following companies are actively conducting clinical trials in individuals with Rett syndrome. This stage may take 6-7 years to complete the 3 phases of clinical trials depending on factors including participant recruitment, length of patient monitoring, and the clarity of results.
Status: In January 2024, Anavex announced topline results from the EXCELLENCE Phase 2/3 study in girls ages 5-17 with Rett syndrome in Australia, Canada, and the U.K. At 12 weeks, the study showed improvement that did not reach statistical significance on the key co-primary endpoint Rett Syndrome Behaviour Questionnaire (RSBQ) between treated and placebo groups and failed to meet the co-primary endpoint on the Clinical Global Impression – Improvement scale (CGI-I). There were no new SAEs reported, and over 91% of trial participants continued into the 48-week open-label study.
Anavex Life Sciences Corp. has also completed a Phase 3 adult study in Australia and the U.K. with topline results expected soon.Previously, they’ve 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 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:
1.2.24 – Anavex Announces Topline Results from Phase 2/3 EXCELLENCE Clinical Study in Pediatric Rett Syndrome
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 March 2024, DepYmed received clearance from the U.S. FDA to initiate a Phase 1 clinical trial for DPM-1003 for the treatment of Rett syndrome. It had previously been granted Orphan Drug designation and conditionally designated under the FDA’s Rare Pediatric Disease program. DPM-1003 is an orally bioavailable small molecule inhibitor that targets the protein tyrosine phosphatase (PTP) family of enzymes that are disrupted in disease like Rett.
To learn more about DepYmed, click here.
Recent News & Updates:
3.19.24 – DepYmed Receives Clearance from U.S. Food and Drug Administration to Initiate Phase 1 Clinical Trial for DPM-1003 for the Treatment of Rett Syndrome
Status: In March 2024, Neurogene Inc. announced the dosing of the third pediatric patient in the U.S. in its Phase 1/2 trial of investigational gene therapy, NGN-401. The treatment has been well-tolerated with no treatment-emergent procedure-related serious adverse events (SAEs) or transgene-related overexpression toxicity to date. They plan to complete dosing of cohort 1 (low dose) in the second half of 2024 and will dose the remaining patients in parallel without a stagger or delay between patients. They plan to report preliminary clinical data from the first patient cohort in Q4 2024, and report data from an expanded number of patients in the 2nd half of 2025.
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. This clinical trial will enroll sixteen (16) female patients with Rett syndrome aged 4-10 split evenly in two cohorts, low dose and high dose. Clinical trial sites include 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 in the U.S. with the Medicines and Healthcare products Regulatory Agency (MHRA) approving their CTA in January 2024 to expand into the United Kingdom in the coming months.
To learn more about Neurogene Inc., click here.
To learn more about enrolling in the Phase 1/2 trial, click here.
Recent News & Updates:
3.4.24 – Neurogene expands clinical trial and removes staggered dosing protocol
1.5.24 – Updates on the U.S. pediatric trial and expansion to the U.K. from Neurogene’s Business Update and 2024 Outlook
12.19.23 – Neurogene closes merger with Neoleukin Therapeutics (Community Letter 7.18.23)
11.30.23 – 1st pediatric patients dosed in U.S. trial of NGN-401
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 (Community Letter)
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. An extension of the trial was announced in March 2024 with all trial participants enrolling in the 52-week extension phase.
To learn more about Neurotech International, click here.
Recent News & Updates:
3.13.24 – All Phase I/II Rett Syndrome Patients to Receive NTI164 Treatment for a Total of 52 Weeks
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: 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.
- Canada: In February 2024, Taysha announced the completion of dosing of the 1st cohort (low dose) in the REVEAL Phase 1/2 adolescent and adult trial. Interim data shared in March 2024 from the first two patients dosed showed that TSHA-102 was generally well-tolerated and there were no treatment-emergent serious adverse events (SAEs) reported. The patients also showed clinical improvement in key efficacy measures at 35- and 19-weeks post-treatment respectively that included autonomic function (sleep and breathing patterns), socialization/communication (social interest, vocalization, and use of eye-driven communication device), motor skills (hand function, sitting unassisted, and hand stereotypies), and seizures (stability and number). The Independent Data Monitoring Committee (IDMC) approved dose escalation of the 2nd cohort (high dose) with dosing of the first patient expected in Q2 2024. Patients in both cohorts 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.
- United States: Taysha has opened enrollment in the U.S. for the REVEAL Phase 1/2 pediatric study of the investigational gene therapy, TSHA-102, and the FDA approved expanding the study to include adolescents and adults (age 12+) in February 2024. Taysha announced the dosing of the first of six Part A female pediatric patients ages 5-8 years old in January 2024 and the IDMC approved moving forward with dosing a 2nd patient. Taysha plans to expand the pediatric study to up to 21 additional patients ages 3-8 years old in Part B of the study. Rush University Medical Center in Chicago is currently recruiting with 7 additional U.S. sites planning to open recruitment soon.
- United Kingdom: The Medicines and Healthcare products Regulatory Agency (MHRA) has authorized the Clinical Trial Application (CTA) for TSHA-102 in pediatric patients, enabling expansion of the ongoing U.S. REVEAL pediatric trial into the U.K. with TSHA-102 received Innovative Licensing and Access Pathway (ILAP) designation. Clinical trial sites will be listed at the same link once available.
To learn more about Taysha Gene Therapies, click here.
To learn more about enrolling in the REVEAL Adult Phase 1/2 Study, click here.
To learn more about enrolling in the REVEAL Pediatric Phase 1/2 Study, click here.
Recent News & Updates:
3.19.24 – Interim Clinical Data from Cohort One Shared on FY23 Financial Results Call
2.29.24 – Study expanded to adolescents and adults in the U.S. and dosing of the 1st adult cohort is complete
1.10.24 – First Pediatric Patient Dosed in U.S. Gene Therapy Clinical Trial
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
STAGE 2: PRE-CLINICAL RESEARCH & DEVELOPMENT
The following companies have a treatment that showed promise during the discovery stage, and is now being more vigorously tested in cell cultures and animal models following regulatory agency mandated requirements. This process lasts 3-5 years and if successful, results in an IND application to begin clinical trials.
ACTX-101 is an AAV9-delivered X-reactivation gene therapy for the treatment of Rett syndrome. In May 2022, Alcyone presented preclinical data showing that 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.
Recent News & Updates:
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.
Recent News & Updates:
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 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.
Recent News & Updates:
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.
Recent News & Updates:
2.15.2023 – Unravel Biosciences announces positive feedback from FDA pre-IND Meeting on RVL001 Rett Syndrome Program
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 is a private biotech company developing therapies based on mitochondrial small-molecule treatments and biomarkers for neurological diseases.
To learn more about Lucy Therapeutics, click here.
Recent 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.
STAGE 1: DRUG DISCOVERY & DEVELOPMENT
The following companies are in the discovery and development stage spanning basic research discoveries in the lab to tests in cell culture or animal models. This stage may include 5-10 years of testing before a new treatment can be developed further.
Dewpoint Therapeutics is a biotechnology company that explores modulating condensates to target diseases across many therapeutic areas, including Rett syndrome.
To learn more about Dewpoint Therapeutics, click here.
Epeius pharma is a cell and gene therapy company developing next generation biological vehicles for delivery of therapeutic proteins into the central nervous system (CNS). They hope to use their novel CNS delivery platform to introduce MECP2 to MECP2 deficient neurons of Rett patients.
To learn more about Epeius Pharma, click here.
IAMA Therapeutics is a pharmaceutical company focused on the discovery, development, and commercialization of novel medicines for children affected by brain disorders.
To learn more about IAMA Therapeutics, click here.
Stoke Therapeutics’ mission is to address the underlying cause of severe diseases by upregulating protein expression with RNA-based medicines. In January 2022, they entered into a partnership with Acadia to discover, develop and commercialize novel RNA-based medicines for the potential treatment of Rett syndrome.
To learn more about Stoke Therapeutics, click here.
Recent News & Updates:
1.10.22 – Stoke Therapeutics and Acadia Pharmaceuticals Collaborate to Pursue RNA Treatment
Vico Therapeutics is exploring taking an RNA editing approach to target Mecp2-R255X. Their therapeutic strategy is based on antisense oligonucleotide-mediated RNA editing to repair mutant MECP2 and reverse symptoms.
To learn more about Vico Therapeutics, click here.
DISCONTINUED OR CANCELED CLINICAL PROGRAMS
The following companies have terminated their Rett syndrome treatment development program.
In October 2021, Novartis terminated its Rett syndrome gene replacement program, OAV201, after pre-clinical data did not support a path forward to human clinical trials per the company’s Q3 2021 Financial Report.
To learn more about Novartis Gene Therapies, click here.
Recent News & Updates:
2.8.21 – IND Submission Update (Community Letter)
8.20.20 – Additional Pre-Clinical Studies Complete (Community Letter)
8.22.19 – AveXis/Novartis Delay Trial and Withdraw IND Application for More Testing (Community Letter)
Due to the challenges presented by COVID-19, GW Pharma discontinued the ARCH Phase 3 global trial of its cannabidiol oral solution for Rett syndrome in November 2020.
To learn more about GW Pharmaceuticals (now Jazz Pharmaceuticals), click here.
Recent News & Updates:
11.12.20 – Trial Closure Announcement (Community Letter)
9.6.19 – Trial Criteria Announcement (Community Letter)
May 2019 – Trial Now Recruiting
In May 2020, Newron canceled its Rett syndrome program after top-line results from its phase 2 STARS clinical study of sarizotan did not demonstrate efficacy on primary and secondary endpoints.
To learn more about Newron Pharmaceuticals, click here.
Recent News & Updates:
5.4.20 – Top-Line Results from STARS Study
4.12.19 – Clinical Trial Enrollment Complete & Thank You (Community Letter)