Treating exudative maculopathy with a single intravitreal injection is the goal that several international research groups have been working toward for years.
Currently, patients affected by exudative maculopathy must follow injection-based therapy with anti-VEGF drugs, which involves injecting a medication directly into the eye (via intravitreal injection) to block VEGF—the main factor responsible for the uncontrolled proliferation of abnormal blood vessels that cause retinal and visual damage typical of the disease.
Anti-VEGF intravitreal therapy has proven to be highly effective and safe, yet the need for frequent injections (typically every 4 to 8 weeks) places a psychological and emotional burden on patients, in addition to imposing significant costs on the healthcare system.
Ophthalmologists and patients are well aware of the emotional and financial toll of anti-VEGF therapy. Recent data show that more than 40% of patients discontinue treatment after the first three years, with serious consequences for their vision.
The search for new therapeutic strategies capable of permanently or long-term counteracting the pathological effects of exudative maculopathy has led to the exploration of gene therapy techniques. These involve delivering therapeutic DNA into the patient’s retinal cells, enabling them to produce the anti-VEGF drug directly within the eye.
This therapeutic DNA would be administered in a single intravitreal injection, allowing for continuous production of anti-VEGF in the eye—potentially eliminating the need for repeated intravitreal injections, or at least drastically reducing their frequency.
The most promising gene therapy for the potential definitive treatment of exudative maculopathy is called Ixo-vec (Ixoberogene Soroparvovec), developed by Adverum Biotechnologies. Once injected, Ixo-vec is expected to provide a long-lasting and effective therapeutic effect without significant adverse events.
A Phase I clinical trial (named OPTIC) and a Phase II trial (named LUNA, currently ongoing) have been conducted to assess the therapy.
In the OPTIC study, most patients remained free from anti-VEGF injections for over three years, an extremely encouraging result. The subsequent LUNA study is designed to evaluate whether lower drug doses combined with enhanced prophylactic regimens can achieve even better outcomes. LUNA aims to determine the optimal dose of Ixo-vec and the most effective local corticosteroid prophylaxis regimen, with or without oral prednisone, to define parameters for future Phase III trials.
At the American Society of Retinal Specialists (ASRS) Annual Meeting held last July in Stockholm, preliminary data from the LUNA study—collected 26 weeks after initiation—were presented.
The data showed that Ixo-vec has a favorable safety and efficacy profile. The drug dose used, lower than in the OPTIC study, resulted in less inflammation while maintaining therapeutic efficacy: 100% of patients experienced either no inflammation or mild inflammation, which was resolved with the study’s prophylactic protocol. Moreover, 76% of patients remained free from intravitreal anti-VEGF injections, maintaining stable visual acuity. The therapy also proved beneficial for patients previously treated with Vabysmo.
Ixo-vec currently represents the most promising therapeutic option for radically changing the treatment landscape for patients with exudative maculopathy.
Adverum Biotechnologies is expected to release 9- and 12-month follow-up data from the LUNA study soon. If these results confirm the 26-week findings, patients with exudative maculopathy may soon have a real chance at long-term vision preservation without having to depend on frequent intravitreal injections.
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