What Is ABBV-RGX-314 Dose 1?
ABBV-RGX-314 Dose 1 is an investigational gene therapy. It is delivered as a subretinal injection, meaning it is administered directly into the eye. This therapy uses an AAV8 vector (adeno-associated virus) to carry a special gene. Once delivered, this gene instructs the eye cells to produce a soluble anti-VEGF protein. This protein is designed to block the activity of vascular endothelial growth factor (VEGF), which is a key factor in the development of abnormal blood vessels in certain eye conditions.
ABBV-RGX-314 Dose 1 is currently being studied in clinical trials for the treatment of various eye conditions, primarily those involving abnormal blood vessel growth in the retina. These conditions include Neovascular Age-related Macular Degeneration (nAMD) and Wet Age-related Macular Degeneration (wAMD). The goal of this gene therapy is to provide a long-lasting treatment option by continuously producing the anti-VEGF protein, potentially reducing the need for frequent eye injections.
Uses and Conditions Under Study
ABBV-RGX-314 Dose 1 is primarily being investigated for the treatment of conditions characterized by abnormal blood vessel growth in the eye, which can lead to vision loss. The most common condition under study is Neovascular Age-related Macular Degeneration (nAMD), also known as Wet Age-related Macular Degeneration (wAMD) or Wet Macular Degeneration. This condition involves the growth of new, leaky blood vessels under the macula, the part of the retina responsible for sharp, central vision. These abnormal vessels can cause fluid leakage, bleeding, and scarring, leading to distorted vision and severe vision loss.
The drug's mechanism of action, which involves producing an anti-VEGF protein, aims to inhibit the formation and leakage of these abnormal blood vessels. By targeting VEGF, ABBV-RGX-314 Dose 1 seeks to stabilize or improve vision in affected individuals. Related conditions also being studied include Choroidal Neovascularization (CNV) and general Age-related Macular Degeneration (AMD) when it involves neovascularization.
Across all related terms, ABBV-RGX-314 Dose 1 is being studied in a total of 9 clinical trials. These trials have enrolled a total of 3,216 participants to evaluate the safety and effectiveness of this investigational gene therapy. The first trial began in February 2017, with the latest trial starting in June 2025.
Dosing
ABBV-RGX-314 Dose 1 is an investigational gene therapy administered as a subretinal injection. This means the medication is delivered directly into the space beneath the retina in the eye. The specific strength of ABBV-RGX-314 Dose 1 is one of several investigational doses being evaluated in clinical trials. Other doses, such as ABBV-RGX-314 Dose 2, Dose 3, and Dose 4, are also under study, often with different formulations (e.g., Commercial Formulation Dose 1, Clinical Formulation Dose 1) or in combination with other treatments like topical steroids.
In clinical trials, ABBV-RGX-314 Dose 1 is typically administered as a single subretinal injection. The exact frequency and long-term dosing regimen are part of the ongoing research to determine the most effective and safe approach for treating conditions like Neovascular Age-related Macular Degeneration. The trials include various treatment arms, such as RGX-314 Treatment Arm (Dose 1), to compare its effects against control groups or other standard treatments like aflibercept or ranibizumab. Currently, there is no information provided regarding specific pediatric dosing or administration frequency (e.g., daily, weekly) beyond the single injection nature of gene therapy.
Side Effects
In a clinical trial (NCT03066258) investigating ABBV-RGX-314 for neovascular age-related macular degeneration (AMD), detailed frequencies of specific individual side effects were not provided. The study reported the total number of participants who experienced any ocular (eye-related) or non-ocular (non-eye-related) adverse events (AEs) or serious adverse events (SAEs) across various treatment cohorts of ABBV-RGX-314. No placebo group was included in this data for direct comparison of side effect rates.
The number of participants who experienced any adverse event or serious adverse event in each cohort was:
- In Cohort 1, 6 participants experienced an AE or SAE.
- In Cohort 2, 6 participants experienced an AE or SAE.
- In Cohort 3, 6 participants experienced an AE or SAE.
- In Cohort 4, 12 participants experienced an AE or SAE.
- In Cohort 5, 12 participants experienced an AE or SAE.
It is important to note that this data represents the count of individuals who experienced at least one adverse event, rather than a list of specific side effects and their frequencies. The total number of participants within each cohort was not provided; therefore, percentages of patients experiencing these events cannot be calculated. Further details regarding the specific types of adverse events were not available in this summary.
Clinical Trial Results
The efficacy of ABBV-RGX-314 was evaluated in a clinical trial (NCT03066258) involving participants with neovascular age-related macular degeneration (AMD). The study assessed changes in visual acuity, central retinal thickness, choroidal neovascularization area, and the need for supplemental injections across five different treatment cohorts.
Visual Acuity (BCVA)
Best Corrected Visual Acuity (BCVA) was measured by the change from baseline in ETDRS letters. An increase in letters indicates improved vision.
- Cohort 1 experienced a mean decrease of 7.6 ETDRS letters.
- Cohort 2 experienced a mean increase of 1.2 ETDRS letters.
- Cohort 3 showed a significant mean increase of 14.0 ETDRS letters.
- Cohort 4 experienced a mean increase of 0.9 ETDRS letters.
- Cohort 5 experienced a mean decrease of 3.8 ETDRS letters.
Central Retinal Thickness (CRT)
Central Retinal Thickness (CRT) was measured by the change from baseline in micrometers (μm). A decrease in CRT generally indicates a reduction in retinal swelling, which is considered beneficial.
- Cohort 1 showed a mean reduction of 88.6 μm.
- Cohort 2 experienced a mean increase of 25.3 μm.
- Cohort 3 showed a mean increase of 2.0 μm.
- Cohort 4 showed a mean reduction of 56.7 μm.
- Cohort 5 showed a significant mean reduction of 108.2 μm.
Choroidal Neovascularization (CNV) Area
The mean change from baseline in the area of Choroidal Neovascularization (CNV) was measured in square millimeters (mm²). A decrease in CNV area indicates a reduction in abnormal blood vessel growth, which is a positive outcome in AMD.
- Cohort 1 showed a mean reduction of 0.4 mm².
- Cohort 2 showed no mean change in CNV area (0.0 mm²).
- Cohort 3 showed a mean reduction of 1.2 mm².
- Cohort 4 showed a mean reduction of 1.1 mm².
- Cohort 5 showed a mean reduction of 0.6 mm².
Supplemental Injections
The annualized rate of supplemental anti-VEGF injections indicates the frequency of additional treatments needed to manage AMD. A lower rate suggests better control of the disease by ABBV-RGX-314.
- Cohort 1 required a mean of 10.3 supplemental injections per year.
- Cohort 2 required a mean of 9.3 supplemental injections per year.
- Cohort 3 required a mean of 2.8 supplemental injections per year.
- Cohort 4 required a mean of 4.4 supplemental injections per year.
- Cohort 5 required a mean of 2.0 supplemental injections per year.
Currently Recruiting Trials
Several clinical trials are currently recruiting participants to further evaluate ABBV-RGX-314 Dose 1, also known as Surabgene Lomparvovec. These studies are designed to assess its safety and effectiveness across different eye conditions.
One such trial, NCT07007065, is a Phase 3 study sponsored by AbbVie. It focuses on Surabgene Lomparvovec in adult participants with neovascular age-related macular degeneration (nAMD), commonly known as "wet" AMD. This condition involves the abnormal growth of new blood vessels in the retina. The study aims to evaluate the drug's impact on injection burden, adverse events, changes in disease activity, and the long-term preservation of visual acuity. It plans to enroll 561 participants, comparing two doses of Surabgene Lomparvovec against a Ranibizumab control group.
Another actively recruiting study, NCT06942520, is a Phase 2 trial led by Sierra Eye Associates. This open-label, randomized, dose-ranging study is investigating RGX-314 (ABBV-RGX-314) in adults with Center Involved - Diabetic Macular Edema (CI-DME). It will compare two doses of RGX-314 against an Aflibercept treatment arm, with an enrollment target of 18 participants.
AbbVie is also sponsoring a pivotal Phase 3 study, NCT05407636, which is evaluating ABBV-RGX-314 as a potential one-time gene therapy for neovascular (wet) age-related macular degeneration (nAMD). This condition is characterized by vision loss due to new, leaky blood vessel formation in the eye. The trial aims to enroll 714 participants and will compare two doses of ABBV-RGX-314 against a control arm.
Finally, a long-term follow-up study, NCT03999801, sponsored by AbbVie, is underway to assess the long-term safety and efficacy of RGX-314 (ABBV-RGX-314) in participants with neovascular age-related macular degeneration. This Phase 2 observational study is designed for individuals who have previously received a single subretinal administration of RGX-314 in a prior clinical trial. It includes a main observational study and a fellow eye treatment substudy, with an enrollment target of 865 participants.
Where to Participate
Clinical trials for ABBV-RGX-314 Dose 1 are actively recruiting across a wide geographic area, with study sites in 33 states, covering 109 cities and a total of 155 locations. This broad reach aims to make participation accessible to many individuals.
Some of the top cities with multiple participating sites include:
- Austin, Texas (4 sites)
- Baltimore, Maryland (4 sites)
- Philadelphia, Pennsylvania (4 sites)
- San Antonio, Texas (4 sites)
- Boston, Massachusetts (3 sites)
- Phoenix, Arizona (3 sites)
- Sacramento, California (3 sites)
- Cleveland, Ohio (3 sites)
- Reno, Nevada (3 sites)
- Germantown, Tennessee (2 sites)
To be eligible for these studies, participants must be between 25 and 89 years of age. All genders are welcome, but healthy volunteers and children are not eligible to participate.
Development Timeline
The journey of ABBV-RGX-314 (also known as Surabgene Lomparvovec) began with its first clinical trial on February 28, 2017. Initially, the development focused on conditions such as IBS-C and hyperphosphatemia, indicating a broad early exploration of its potential.
Over time, the focus shifted and expanded significantly, particularly into ophthalmology. The pipeline grew to include various forms of age-related macular degeneration (AMD), such as neovascular (wet) AMD (nAMD, wAMD), and choroidal neovascularization (CNV). More recently, its scope has broadened further to address diabetic macular edema (DME) and diabetic retinopathy (DR).
AbbVie has been the primary sponsor, leading seven of the nine total trials for ABBV-RGX-314, with REGENXBIO Inc. and Sierra Eye Associates also contributing to its development. The program has progressed through various stages, including one Phase 1/Phase 2 study, five Phase 2 studies, one Phase 2/Phase 3 study, and two pivotal Phase 3 studies, reflecting its advancement towards potential approval.
Cumulatively, these studies have aimed to enroll a total of 3,216 participants, with the latest trial initiated on June 5, 2025, demonstrating ongoing commitment to understanding this investigational treatment.