AAVantgarde Bio Doses First Patient in Trial for Usher Syndrome Gene Therapy AAVB-081
AAVB-081 is intended to address retinitis pigmentosa that results from Usher syndrome type 1B.
AAVantgarde Bio has dosed the first patient in the first-in-human phase 1/2 LUCE-1 clinical trial (NCT06591793) evaluating AAVB-081 (also known as AAV8.MYO7A), an investigational adeno-associated virus (AAV) vector-based gene therapy, for the treatment of retinitis pigmentosa associated with Usher syndrome type 1B (USH1B).1
AAVB-081 is a dual hybrid product comprised of 2 AAV8 vectors that is intended to provide a functional copy of the disease-targeted gene, Myo7A. The vectors each transport half of the transgene, which is too large to be carried in a single AAV vector, for recombination within the cell. The gene therapy product is administered to patients subretinally.
The multicenter, open-label LUCE-1 trial takes the form of a dose escalation study. Participants will be treated at 1 of 3 planned dose levels. The trial, which is expected to enroll 15 patients in total, is open to patients with USH1B who are aged 18 to 50 years old. The study’s primary end point is the number and severity of treatment-related adverse events and the secondary end points include the changes from baseline in microperimetry and static perimetry. The timeframe for all end points is 61 months. According to the clinicaltrials.gov page, which was most recently updated on September 19, 2024, the study is currently recruiting at University of Campania Luigi Vanvitelli in Naples, Italy. Two sites in London are listed as not yet recruiting patients.
“I am delighted to be involved as principal investigator in this first-in-human phase 1/2 clinical study of AAV-081 for patients with retinitis pigmentosa related to USH1B,” Francesca Simonelli, the head of the Ophthalmology Unit at the University Hospital of Campania Luigi Vanvitelli, said in a statement.1 “Through this innovative program, we aim to revolutionize our approach to understanding and treating these underserved patients. We are poised to generate robust evidence that will not only advance scientific knowledge, but also directly impact patient care.”
AAV-081 is not the only advanced therapeutic currently in development for complications related to the different forms of Usher syndrome. According to the Usher Syndrome Coalition, findings from research related to USH1B, Usher syndrome Type 1F, and Usher syndrome type 2C, and other forms, have been announced over the past 2 years.2
Notably, Zheng-Yi Chen, DPhil, associate scientist, Eaton-Peabody Laboratories, Mass Eye and Ear, and associate professor, Otolaryngology–Head and Neck Surgery, Harvard Medical School, and his colleagues are currently conducting preclinical research focused on a gene-editing approach for the treatment of Usher syndrome type 2A (Ush2A). CGTLive® recently interviewed Chen about his lab’s research for Usher Syndrome Awareness Day, which is observed annually on September 21.
“Our work focuses on the development of gene editing to treat hearing loss and vision loss in Ush2A, the most common form of Usher syndrome,” Chen told CGTLive. “Ush2A patients suffer from congenital hearing loss and progressive vision loss. The Ush2A gene has a large size for which the conventional AAV vector-based gene therapy method, similar to the one used in our OTOF clinical trial, does not work. Instead, we used a gene-editing strategy called exon skipping, to target the DNA sequence that harbors the most frequent Ush2A mutations. By this approach, we can eliminate the mutation-carrying DNA and restore the production and function of the Ush2A protein missing in patients. We have shown that in the cultured inner ear organ and in a transgenic mouse model, this strategy leads to functional inner ear sensory cells (hair cells). We are working with our collaborator, Drs. Qin Liu and Jason Comander of Mass Eye & Ear and Harvard Medical School, to demonstrate the restoration of hearing and vision in Ush2A mouse models.”
