Neurogene shares fall on Rett syndrome gene therapy data
Rachel McMinn, Neurogene's founder and chief executive
Neurogene has reported encouraging efficacy results with its gene therapy for rare genetic disorder Rett syndrome, but investors' concerns about safety seem to be weighing on its share price.
The New York biotech's update focused on data from four patients treated with a low dose of Neurogene's NGN-401 therapy in female Rett syndrome patients, which it said showed "meaningful gains of skills and developmental milestones."
Despite the positive assessment, shares in the company fell almost 44% after the announcement, apparently because of one serious adverse event in one of two patients treated with a higher dose of NGN-401, which some investors felt could make the therapy less compelling than a rival candidate from Taysha Gene Therapies, whose stock rose 20%.
The sell-off in Neurogene could, however, also have been prompted in part by Neurogene's decision to end the development of NGN-101, a gene therapy for Batten disease, after the FDA declined to give its blessing to a streamlined regulatory pathway for the programme.
In a statement, Neurogene said the serious adverse event with NGN-401 was associated with a known risk of adeno-associated virus (AAV) gene therapies. While it did not reveal the specific side effect, AAV vectors are known to carry a risk of liver damage and inflammation.
Rett syndrome is a devastating neurological disorder caused mainly by mutations in the MECP2 gene found on the X chromosome.
The disease causes deficits in brain function that lead to behavioural problems, a rapid decline in the ability to speak and carry out manual tasks, as well as seizures, curvature of the spine, and sleep disturbances. It affects about 15,000 girls and women in the US and 350,000 worldwide.
NGN-401 is designed to deliver a working version of MECP2 to Rett patients and is administered as a one-shot intra-cerebroventricular infusion. It is worth noting that excessive production of MECP2 carries its own risk of toxicity, such as epileptic seizures.
In the phase 1/2 trial, the first four patients all achieved a "much improved" rating on the clinician-rated Clinical Global Impression Scale of Improvement (CGI-I) from baseline – a two-point improvement over baseline, where a score of three or less is considered "clinically meaningful," according to Neurogene.
They also all improved on the caregiver-completed Rett Syndrome Behaviour Questionnaire (RSBQ), with gains of 28% to 52% on baseline scores.
Neurogene also said it has started an adolescent/adult cohort enrolling three participants aged 16 and above at the high dose "to gain initial data on the potential of NGN-401 to treat a broader patient population."
It aims to complete enrolment of the full complement of eight low-dose paediatric patients before the end of the year and report additional data in the second half of 2025. Details of its registrational trial design should be available in the first half of next year.
"Today marks an important day for Neurogene and the Rett syndrome community," said Rachel McMinn, Neurogene's founder and chief executive.
The data "demonstrated meaningful gains of skills and developmental milestones in core clinical domains of Rett syndrome, which are not expected to occur when compared to and contextualised against the natural history" of the disease, she added.
