The standard treatment for wet age-related macular degeneration (wet AMD) is a relentless cycle. To save the sharp, central vision required to read or recognise a face, patients must endure injections directly into the eye, often every one or two months, indefinitely.

This is a continuous, draining battle.

A new approach, now advancing through clinical trials, has been engineered to solve this problem. A single-administration gene therapy, known as 4D-150, has a powerful goal: to significantly reduce this treatment burden with a single dose.

The problem: a relentless cycle of injections Wet AMD occurs when abnormal blood vessels leak fluid beneath the macula, rapidly damaging sight. While current anti-VEGF injections can stop this leakage, their effect is temporary. This ties patients to a demanding schedule that comes at a significant physical, logistical, and emotional cost. It is a management strategy, not a solution.

The scientific goal: a single, durable treatment This burden has driven the search for a better way. The objective is to engineer a treatment that controls the disease for years, not months, from a single administration. This search has led directly to one of the most advanced fields in medicine: gene therapy.

How gene therapy aims to work Instead of repeatedly adding a manufactured drug, gene therapy is designed to turn the eye into its own, self-regulating medicine factory. The process involves delivering a new set of genetic instructions to the retinal cells. The scientific hypothesis is that a single administration could then provide a steady supply of the necessary therapeutic protein for multiple years, right where it is needed most.

The engineering of 4D-150
4D-150 is a clear example of this principled, engineering-led approach. It is designed as a comprehensive attack on key vessel growth factors that drive the disease:

• A specialised delivery system: It uses a custom-engineered vector, R100, designed specifically for effective delivery to retinal cells after an injection.

• A dual-action payload: The genetic code it carries instructs the retinal cells to produce two different molecules. The first is aflibercept, a proven therapeutic protein. The second is a molecule that inhibits VEGF-C, another key factor in vessel growth.

This is a multi-pronged approach, engineered to block four different factors in the VEGF pathway.

The status: advancing through Phase 3 trials
A promising idea is not a treatment. The journey is long and requires rigorous proof. 4D-150 is now advancing through Phase 3 clinical trials, a pivotal stage of testing required before regulators can consider it for approval. The first data from these trials are not expected until early 2027.

Data from the earlier Phase 2 trial was encouraging. The key finding was a dramatic reduction in treatment burden: patients maintained their vision (with an average gain of +2.2 letters) while requiring over 80% fewer supplemental injections over one year. For newly diagnosed patients, this reduction was 94%.

The most common adverse event was mild, treatable inflammation within the eye, occurring in a small percentage of patients, with no serious vector-related events reported.

What this research could mean for future care

While this therapy is not yet available and its ultimate success and long-term durability are not yet proven, the development of treatments like 4D-150 represents a significant scientific effort to shift the paradigm of wet AMD care.

The objective of this research is a future where the treatment burden is significantly reduced, transforming the standard of care from a lifelong battle into a single administration with the goal of multi-year durability.

Sources

• 4DMT Presents Positive 52-Week Results from Phase 2b Cohort of PRISM Wet AMD Study and Long-term Durability Data Supporting 4D-150 4FRONT Global Registration Program

• 4DMT Announces First Patients Enrolled in 4FRONT-1 Phase 3 Clinical Trial Evaluating 4D-150 in Wet AMD

• 4DMT Announces Accelerated 4D-150 Phase 3 Development in Wet AMD and Streamlined Organization to Drive Late-Stage Execution

• Anti–Vascular Endothelial Growth Factor Drugs for Age-Related Macular Degeneration

• Real-World Injection Intervals in Wet AMD

• Wet AMD Treatment