First Patient Dosed With KH631 Gene Therapy in Phase 1 Trial of Wet AMD


The phase 1 VAN-2201 clinical trial (NCT05657301) is assessing the AAV-delivered gene therapy from Chengdu Origen Biotechnology and Vanotech in 5 dose cohorts of 25 total patients.

Jeffrey S. Heier, MD, a principal investigator in the VAN-2201 trial and the director of the Vitreoretinal Service and of Retina Research at Ophthalmic Consultants of Boston

Jeffrey S. Heier, MD

The first patient with wet age-related macular degeneration (wet AMD, or nAMD) has been dosed in the ongoing phase 1 VAN-2201 clinical trial (NCT05657301) of the investigational treatment KH631, according to an announcement from the codevelopers of the single administration gene therapy, Chengdu Origen Biotechnology and Vanotech.1

KH631 is designed to deliver a targeted protein to block vascular endothelial growth factor (VEGF)—an approach taken by the standard of care treatments for those with neovascular AMD, which has been shown to improve vision—via an adeno-associated viral vector.2 The companies also expressed that the single placement of the VEGF inhibitor product has the potential to reduce the patient burden of regular intraocular injections.

"I am excited to participate as a principal investigator in this important study. Dosing the first patient is an important milestone in the development of the single-administration gene therapy approach, which may hold promise to our patients in need of frequent treatment for their retinal diseases," Jeffrey S. Heier, MD, a principal investigator in the VAN-2201 trial and the director of the Vitreoretinal Service and of Retina Research at Ophthalmic Consultants of Boston, said in a statement.1

The multicenter, open-label, dose-escalation clinical trial will be conducted in the United States, and aims to assess the safety, tolerability, and efficacy of KH631 as a single-administration gene therapy for an enrollment of 25 patients with previously treated wet AMD. Five dose cohorts are planned to be included in the study, with approximately 5 patients per cohort, who will be seen monthly until the primary end point at 24 weeks, and then through week 52. Those enrolled will complete regular visit follow-ups until the 104-week visit. The trial is expected to conclude in September 2027.

CLINICAL TRIALS IN PROGRESS: REGENXBIO’s ABBV-RGX-314 Trials Aim to Reduce Treatment Burden in Inherited Retinal Diseases

Patients will be excluded if they have had any prior non-intravitreal anti-VEGF ocular or systemic treatment (investigational or approved) or surgery for the treatment of neovascular AMD; retinal pigment epithelial tears or rips at screening; any history or presence of vitreous hemorrhage, or a history of intraocular or periocular surgery in the prior 3 months; any disorder preventing visual acuity improvement; any other cause of choroidal neovascularization; prior pars plana vitrectomy or scleral buckling or retinal detachment surgery; macular hole, epiretinal membrane or vitreomacular traction; full thickness macular hole; prior trabeculectomy or other filtration surgery; or use of long-acting intraocular steroids, including implants, within 6 months prior to enrollment.

Key Takeaways

  1. The phase 1 VAN-2201 trial has dosed its first patient with KH631, a single-administration gene therapy aiming to reduce the treatment burden for wet age-related macular degeneration (wet AMD).
  2. KH631 employs an adeno-associated viral vector to deliver a targeted protein that blocks VEGF, a key player in neovascular AMD. Preclinical studies demonstrate prolonged transgene retention, preventing disease progression.
  3. The multicenter trial, led by principal investigator Jeffrey S. Heier, MD, will assess KH631's safety, tolerability, and efficacy as a 1-time treatment.

In preclinical studies of wet AMD disease models, the data from which were published in November 2023 in Molecular Therapy, the administration of KH631 resulted in retention of the transgene product in the retina for prolonged periods and prevented the disease progression.3 The investigators noted that “at a low dose of 3 × 108 vg/eye, [treatment] resulted in remarkable retention of the transgene product in the retina and prevented the formation and progression of grade IV CNV lesions. Furthermore, sustained transgene expression was observed for more than 96 weeks.” All told, the data supported the continued assessment of the treatment as a potential one-time, low-dose option for wet AMD.

"Dosing our first patient in the VAN-2201 phase 1 trial is an important milestone in the advancement of KH631 by exploring the potential of single-administration gene therapy as [a] treatment for wet AMD. KH631 is designed to deliver anti-VEGF continuously to the retina, with the potential to provide sustained levels that can control the disease," Avner Ingerman, MD, the chief medical officer of Vanotech, said in a statement.1

1. Chengdu Origen and Vanotech Announce First Patient Dosed in VAN-2201 Phase 1 Trial of Gene Therapy for Wet Age-Related Macular Degeneration. News release. November 20, 2023. Accessed November 22, 2023.
2. KH631: A Gene Therapy Product. Chengdu Kanghong Pharmacetucal group. Accessed November 22, 2023.
3. Ke X, Jiang H, Li Q, et al. Preclinical evaluation of KH631, a novel rAAV8 gene therapy product for neovascular age-related macular degeneration. Mol Ther. 2023;31(11):3308-3321. doi:10.1016/j.ymthe.2023.09.019
Related Videos
Jacques Galipeau, MD, on Highlights from ISCT 2024’s Presidential Plenary
Zheng-Yi Chen, DPhil, on International Collaboration on Clinical Trials
Shankar Ramaswamy, MD, the cofounder, chairman, and CEO of Kriya Therapeutics
Zheng-Yi Chen, DPhil, on Looking Deeper Into Effects of Gene Therapy on OTOF Deafness
Arshad Khanani, MD
Alfonso Sabater, MD, PhD
Shankar Musunuri, PhD
Ula V. Jurkunas, MD
Alfonso Sabater, MD, PhD, on Bringing Gene Therapy to Ophthalmology
Shankar Musunuri, PhD
© 2024 MJH Life Sciences

All rights reserved.