A new approach to DME treatment

For those struggling with vision loss due to diabetic macular edema (DME), new research brings more hope. The Food & Drug Administration (FDA) has granted regenerative medicine advanced therapy (RMAT) designation to a gene therapy called 4D-150 for the treatment of DME, according to a press release from 4D Molecular Therapeutics, a leading late-stage biotechnology company advancing durable and disease-targeted therapeutics.

DME is a serious complication of diabetes where fluid builds up in the macula (the central part of the retina responsible for sharp, detailed vision). Untreated, the condition can lead to loss of sight .

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But the current DME treatment is both time-consuming and invasive, involving shots to the eye every six weeks to several months. “People with DME usually have other health issues and are less likely to continue to show up for ongoing, time-consuming treatment as they are also younger and of working age,” says Robert Kim, M.D., the chief medical officer at 4D Molecular Therapeutics and an associate clinical professor of ophthalmology at University of California in San Francisco. “The RMAT designation for 4D-150 provides a fast track for a potential treatment that can reduce the treatment burden for those with DME, while preserving their vision.”

RMT is a designation the FDA gives to certain drug candidates intended to treat serious or life-threatening conditions, per the 21st Century Cures Act. “It’s applied to cutting-edge treatments, like gene therapy, that the FDA deems as an innovative treatment for a serious health problem,” explains Dr. Kim. “It helps speed up the review and approval process for the treatment by providing more guidance and communication with the FDA throughout the clinical trial and regulatory process.” In a nutshell, it means patients could have access to the therapy much earlier than expected.

So how exactly does the 4D-150 therapy work for DME? “It targets retina cells where DME occurs and transforms the cells to produce their own therapy aflibercept —the active ingredient in the current standard of care anti-VEGF (anti-vascular endothelial growth factor)—treatment for years, if not the rest of a patient’s life,” says Dr. Kim. “As it’s given as a one-time routine eye injection in the ophthalmologist’s office, it aims to dramatically reduce the frequency of anti-VEGF treatments required to manage the disease.”

The RMAT designation for 4D-150 is based on the results of the ongoing SPECTRA study in DME, says Dr. Kim. “Through 32 weeks of study, 4D-150 continues to be well tolerated with no inflammation in the eye observed,” he says. “It demonstrated a reduction in the fluid build-up in the retina that impacts vision, leading to vision gains. Plus, patients at the dose chosen for Phase 3 needed 86% less injections to control their disease compared to the current standard of care.”

John W. Kitchens, M.D. , an ophthalmologist at Retina Associates of Kentucky, part of the EyeCare Partners Network, in Lexington, KY, who was not involved in the study, agrees that the downside of the first-line anti-VEGF therapy is the number of injections that may be needed to control the disease, because patients with DME have chronic underlying damage to the retinal vasculature (the network of blood vessels in the retina).

That doesn’t mean anti-VEGF therapy isn’t an effective treatment for DME . “In the majority of patients, it can improve visual acuity (a measurement of how clearly a person can see objects, typically at a distance) and in 30% to 40% of cases, restore it significantly,” says Dr. Kitchens. “Anti-VEGF therapy can also improve the severity scores of diabetic retinopathy , a diabetes complication that can cause blindness if left untreated.”

However, while anti-VEGF therapy can improve swelling and restore vision, edema can recur and visual gains can be lost as the medication wears off, requiring frequent injections. “By offering the possibility of a single intravitreal injection that could help patients with DME for multiple years, the 4D-150 gene therapy is something to get excited about,” Dr. Kitchens says. Less frequent treatments also reduces the burden on clinics, he adds.

The RMAT designation in DME follows the RMAT designation granted for 4D-150 in wet age-related macular degeneration ( wet AMD ), a serious form of macular degeneration where abnormal blood vessels grow into the macula. 4D-150 is the first investigational medicine to be granted the designation in both indications, according to a news release from 4D Molecular Therapeutics.

“If any indication from the Phase 2 wet macular degeneration studies is an indication of how this treatment might work, gene therapy holds a lot of promise,” says Dr. Kitchens. “The Phase 2 studies for wet macular degeneration showed 80% of patients had a significant decrease in treatment burden after the application of the 4D-150 gene therapy.”

Millions of people around the world are living with wet AMD or DME. With the development of 4D-150, they could reap the benefits: reducing the burden of frequent injections while preserving their vision.

FDA Grants RMAT to New Gene Therapy: 4DMT. (2025.) “4DMT Announces RMAT Designation Granted by FDA for 4D-150 for DME.” ir.4dmoleculartherapeutics.com/news-releases/news-release-details/4dmt-announces-rmat-designation-granted-fda-4d-150-dme

Regenerative Medicine Advanced Therapy Designation: Food & Drug Administration. (2023.) “Regenerative Medicine Advanced Therapy Designation.” fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/regenerative-medicine-advanced-therapy-designation

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