In an efficacy analysis involving four patients who received a low dose of NGN-401 (1E15 vg), each participant reported significant improvements, achieving a score of “much improved” on the Clinician Global Impression Scale of Improvement (CGI-I), with all scores reflecting an impressive rating of 2. Furthermore, this cohort exhibited notable enhancements in the caregiver-completed Rett Syndrome Behavior Questionnaire (RSBQ), showcasing improvements that varied between 28% and 52% when compared to their baseline measurements.
“Today is a pivotal milestone for Neurogene and the Rett syndrome community as we unveil encouraging interim data for NGN-401 from our low-dose cohort,” stated Rachel McMinn, PhD, founder and chief executive officer of Neurogene. “The initial four participants have demonstrated tangible gains in essential skills and developmental milestones in the key clinical areas impacted by Rett syndrome, which are typically not anticipated when aligned with the disease’s natural progression.” She emphasized the uniformity of data across various measurement scales and highlighted the consistent effects observed among patients, regardless of their diverse clinical features at the beginning of the trial.
The additional efficacy data revealed that all participants made gains in fundamental clinical domains of Rett syndrome, including hand function/fine motor skills, language/communication abilities, and ambulation/gross motor skills. These developments encompassed complex capabilities that are infrequently achieved in this demographic and are seldom reintegrated following developmental regression, as indicated by the NIH-sponsored studies on the natural history of Rett syndrome. Notably, the acquisition of new skills and milestones has not only expanded but has also intensified over time, further illustrating the positive impact of the treatment.
“Rett syndrome represents a profoundly devastating neurodevelopmental disorder that poses significant challenges for both patients and caregivers, particularly given the absence of treatment options that target the disease’s root causes,” expressed Aleksandra Jacobs, MD, PhD, a neurology professor at Albert Einstein College of Medicine and director of the Center for Rett Syndrome at Montefiore Medical Center. “The comprehensive outcomes presented today regarding NGN-401 gene therapy are unprecedented in the landscape of Rett syndrome treatment. Remarkably, these early participants achieved developmental skills after undergoing treatment—a period during which the natural history of Rett syndrome predicts that affected girls would not show progress. I eagerly anticipate the further advancements in this program and the additional data that will emerge.”
Neurogene shared several important updates regarding the clinical trial, stating that it anticipates completing enrollment for the low-dose pediatric cohort, consisting of eight participants, by the final quarter of 2024, with expectations for further interim phase 1/2 data to be unveiled in the latter half of 2025. Moreover, the company has initiated a new cohort for adolescents and adults, targeting three participants aged 16 and older, aimed at exploring the therapeutic potential of high-dose NGN-401. Additionally, Neurogene announced that it has reached alignment with the FDA regarding its potency assay strategy and manufacturing scale-up plans for NGN-401, which will support its trajectory towards a future trial and potential product launch.
How do the outcomes of NGN-401 challenge the typical progression expected in patients with Rett syndrome?
**Interview with Dr. Rachel McMinn, CEO of Neurogene**
**Interviewer**: Thank you for joining us today, Dr. McMinn. You’ve recently announced some promising interim data concerning NGN-401. Can you share more about what these initial findings reveal?
**Dr. McMinn**: Absolutely, and thank you for having me. We’re excited to share that in our low-dose cohort of NGN-401 involving four patients, each participant reported significant improvements on the Clinician Global Impression Scale of Improvement. All participants were rated as “much improved,” which is a remarkable outcome, especially considering the challenges typically associated with Rett syndrome.
**Interviewer**: That’s impressive indeed. You mentioned improvements in various clinical domains related to Rett syndrome. Can you elaborate on what specific skills or areas were enhanced?
**Dr. McMinn**: Certainly! We observed noteworthy gains in fundamental areas such as hand function and fine motor skills, language and communication abilities, and even gross motor skills like ambulation. These improvements represent not only significant strides for these patients but also reflect advancements that are seldom seen in this population, especially after developmental regression.
**Interviewer**: It’s heartening to hear that. How does the data you’ve gathered align with what is typically expected in the natural progression of Rett syndrome?
**Dr. McMinn**: Generally, we do not anticipate such improvements due to the nature of the disease. Our findings underscore the efficacy of NGN-401 in reversing certain aspects of the condition. Not only have patients made gains, but the consistency of the results across various measurement scales is something we are particularly proud of, regardless of the diverse initial clinical features among participants.
**Interviewer**: What feedback have you received from the caregivers involved in this study regarding the changes observed in their loved ones?
**Dr. McMinn**: Caregivers have reported remarkable shifts, most notably reflected in the Rett Syndrome Behavior Questionnaire. We witnessed improvements ranging from 28% to 52% compared to their initial assessments. This feedback is invaluable as it highlights the real-life impacts of these clinical improvements.
**Interviewer**: This certainly seems like a pivotal moment for Neurogene and the Rett syndrome community. What are the next steps moving forward with NGN-401?
**Dr. McMinn**: We’re committed to furthering our research and expanding our trials to include more participants. Our objective is to validate these encouraging findings and explore the full potential of NGN-401. It’s a crucial time for advancing our understanding and treatment options for Rett syndrome.
**Interviewer**: Thank you for sharing such encouraging news, Dr. McMinn. We look forward to seeing the continued developments from Neurogene.
**Dr. McMinn**: Thank you for the opportunity. We’re hopeful for what lies ahead and grateful for the support of the Rett syndrome community.
