4DMT Planning Phase 3 Clinical Trial for Wet AMD Gene Therapy
Research News
Known as 4D-150, the wet AMD gene therapy performed well in a Phase 2b clinical trial.
4D Molecular Therapeutics (4DMT), a company developing gene therapies for retinal diseases and other conditions, has announced plans to launch 4FRONT, a 500-patient Phase 3 clinical trial for 4D-150, its emerging gene therapy for the wet form of age-related macular degeneration (AMD). The company plans to begin dosing patients in the first quarter of 2025. The decision to advance 4D-150 into a Phase 3 trial is based in part on favorable 52-week results for safety and efficacy from a Phase 2b trial which enrolled 30 patients.
The goal of 4D-150 is to reduce the treatment burden for wet AMD, a condition characterized by the growth of damaging leaky blood vessels underneath the retina. Several therapies approved by the US Food & Drug Administration (FDA) and the European Medicines Agency are effective in blocking blood vessel growth but require regular administration (every one to six months) into the eye. The 4D-150 gene therapy is designed to be a one-time injection into the vitreous, the soft gel in the middle of the eye. Gene therapies are designed to work for many years, perhaps the life of the patient.
Intravitreal injections are typically administered in a doctor’s office.
4D-150 uses a proprietary adeno-associated virus (AAV), which works like a vast shipping container system, to deliver copies of two genes into retinal cells. The two therapeutic genes continually express four proteins in the cells to block four types of vascular endothelial growth factors (VEGFs) — factors which drive the growth of the harmful blood vessels.
In the Phase 2b clinical trial for 4D-150, 70 percent of patients didn’t need a rescue injection of an existing wet AMD therapy over a 52-week period.
AMD is the leading cause of blindness in people 55 and older in developed countries. It affects approximately 200 million people globally. AMD always begins as the dry form with the accumulation of lipid deposits called drusen underneath the retina. Many people with drusen will never have vision loss. In some people with dry AMD, the build-up of drusen can lead to retinal cell death and central vision loss, an advanced from of dry AMD known as geographic atrophy. People with dry AMD can also develop wet AMD which also leads to central vision loss.
