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A new era for MacTel: Clinicians react to FDA approval of revakinagene taroretcel-lwey
Insights shed light on what the approval means for providers and their patients affected by this neurodegenerative retinal disease
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The approval of revakinagene taroretcel-lwey (Encelto; Neurotech Pharmaceuticals) as the first and only FDA-approved treatment for macular telangiectasia type 2 (MacTel) marks a significant milestone for patients with the progressive retinal disease.1 The implantable device uses encapsulated cell therapy (ECT) technology to continuously deliver therapeutic doses of ciliary neurotrophic factor (CNTF) to the retina, helping to slow disease progression. The approval was based on the results from two phase 3 trials, which showed that after implantation, revakinagene taroretcel-lwey significantly slowed the loss of macular photoreceptors in patients with MacTel over a 24-month period.1
With the treatment expected to be available in the US starting in June 2025, the EyeCare Network reached out to clinicians and members of its respective editorial advisory boards for their insights on how the FDA approval for this device might change the treatment landscape for patients with MacTel.
“Approval for this treatment for this disease that is incurable right now...will be a wonderful situation for retina specialists and for the patients. First of all for the patients, and then for the retina specialists who will be able to provide treatment for this incurable disease,” said Anat Loewenstein, MD, professor and head of retina, Division of Ophthalmology, Tel Aviv Medical Center, VP Ambulatory Services; president, EURETINA; Sydney Fox Chair of Ophthalmology, Tel Aviv University; and president, Israeli Ophthalmological Society, Tel Aviv, Israel. She is also a member of the editorial advisory board for Modern Retina.
“By delivering continuous neurotrophic support to the retina, this device offers a novel approach that could slow disease progression and help preserve vision in affected individuals. This shift from passive monitoring to an active treatment strategy is a game-changer for both patients and clinicians,” said Rishi P. Singh, MD, FASRS, who is vice president/chief medical officer of Martin North and South Hospitals; professor of ophthalmology, Cleveland Clinic Lerner College of Medicine; Cleveland Clinic Martin Health in Stuart, Florida. He is also a member of the editorial advisory board for Modern Retina.
“It's a 100% game changer that we can delay [progression],” agreed Martin Friedlander, MD, PhD, who is professor, Department of Molecular Medicine, Scripps Research Institute; chief, Retina Services, Division of Ophthalmology, Scripps Clinic; and president, Lowy Medical Research Institute (LMRI), La Jolla, CA. “In many of the patients we see an absolute halting of progression of disease, which is very exciting. And so if you can preserve useful normal vision for a decade or two, that's very meaningful for these patients.”
Friedlander recently presented an update on data for this MacTel treatment at the 2025 Angiogenesis, Exudation, and Degeneration meeting, held virtually in February.
RELATED: Angiogenesis 2025: Encapsulated cell therapy for MacTel shows long-term efficacy in phase 3 trials
Neurotech’s ECT platform is a cell-based gene therapy delivery system designed to provide long-term, sustained delivery of therapeutic proteins for the treatment of chronic eye diseases, according to a company news release.1 The platform consists of a small, semi-permeable capsule containing proprietary allogeneic retinal pigment epithelium (RPE) cells genetically engineered to produce specific therapeutic proteins for targeted disease treatment. The capsule is surgically implanted. Once in place, the capsule’s semi-permeable exterior membrane allows essential nutrients to enter, while also permitting the therapeutic proteins to exit into the eye where they can travel to the retina located at the back of the eye. The exterior membrane protects the encapsulated RPE cells from the host's immune system, contributing to their survival and functionality over time.
“As with any novel surgical implantation, there is a learning curve for surgeons, particularly in terms of placement technique and patient selection,” Singh said. “However, the procedure builds on existing vitreoretinal surgical approaches, making it a feasible addition to a retina specialist’s surgical repertoire. With appropriate training, adoption should be relatively smooth for experienced surgeons.”
Increased awareness and diagnosis of MacTel
The availability of an FDA-approved treatment is likely to drive greater awareness of MacTel among eye care professionals.
“Historically, MacTel has been underdiagnosed due to its subtle clinical presentation, but the introduction of an intervention will encourage earlier detection and referral patterns among ophthalmologists and optometrists,” Singh said. This, in turn, could lead to improved patient outcomes as we diagnose and manage the disease at earlier stages, he noted.
“It is very exciting to have new developments and treatments for conditions with no prior remedies,” said Mohammad Rafieetary, OD, FAAO, Charles Retina Institute in Memphis, Tennessee.
Now eye care providers can inform patients suffering from this potentially debleating condition, there is hope for better outcomes, he added.
“Although MacTel is considered a rare disease, it is probably more common than we know. The underdiagnosis is mostly due to challenges in the detection of this neurodegenerative retinal disease,” Rafieetary noted.
In the early stages, the patient is often asymptomatic and the signs of the disease are very subtle. In the late or neovascular stage when the patient is symptomatic the condition may be misdiagnosed as macular degeneration or retinal vascular disease, he added.
“Optometrists can face challenges in the diagnosis of MacTel if they are not familiar with its clinical and diagnostic findings, including OCT biomarkers of MacTel,” Rafieetary said. “Upon diagnosis of MacTel the patient should be referred to a retina specialist and find out if their retina specialty resource is actively seeking out patients with MacTel for this newly FDA-approved treatment.”
Rafieetary encourages patients, who may be concerned about MacTel and want to know if this new therapy is right for them, to “read about the pros and cons of ECT to deliver CNTF therapy. Also search for references on MacTel diagnosis and management.”
“I think we're already seeing that [increased interest and awareness],” said Friedlander is also president of the Lowy Medical Research Institute (LMRI) in La Jolla, California. “LMRI is a private, nonprofit, privately funded research institute, which was endowed by the Lowy family, who approached us almost 20 years ago when they had one of their sons diagnosed with macular telangiectasia. At the time we knew virtually nothing about the disease other than we thought it was a retinal vascular disease.
“We have over 4000 patients enrolled in our MacTel Registry,” Friedlander added. This is a disease with a prevalence of 0.04% so it's not a common disease, an orphan disease, but we have many, many patients who are involved with our group. There's a huge effort ongoing in terms of informing the public and physicians.”
Friedlander and Singh note this approval as a significant step forward, not just for MacTel but for the broader field of retinal neuroprotection.
“By demonstrating the potential of sustained drug delivery to support retinal neurons, this device could pave the way for future treatments targeting other neurodegenerative retinal conditions, such as geographic atrophy in age-related macular degeneration or inherited retinal diseases,” Singh said.
It underscores the growing recognition of neuroprotection as a viable therapeutic strategy in ophthalmology, Singh added.
“We view the Neurotech device as a platform technology which will be useful for delivering not only neurotrophics, but perhaps other molecules, like angiostatics or other neurotrophics other than CNTF to treat other neurovascular glial degenerative diseases like glaucoma, age-related macular degeneration, retinitis pigmentosa,” Friedlander said.
“We’ve gone from thinking of MacTel as a localized retinal vascular disease to a systemic neurodegenerative disease,” he said. “About 5% of our patients have causative genetic mutations involved in serine metabolism. And we know that at least in some of these cases, serine is not utilized properly, and serine is a building block for many of the lipids that are in your body. You do not live if you don't have a proper lipid profile.”
From extensive metabolomic, genetic, and transcriptomic studies on patients with macular telangiectasia, “we know virtually all MacTel patients have decreased levels of serine and abnormalities in their lipid profiles, and we know that by modulating these various components of these pathways, we can actually normalize these patterns,” Friedlander added.
The hope is that perhaps by normalizing that clinicians can also normalize the vision loss, he said.
“We know a certain subpopulation of MacTel patients have something called HSA, hereditary sensory and autonomic neuropathy, which is a peripheral neuropathy with the identical causative genetic mutation causing HSA, and that we observe also in patients with MacTel,” Friedlander said. “We're learning a lot about the disease, and this comes through basic science, which is being done here at LMRI, as well as about a dozen laboratories that we support research wise in terms of trying to understand more about the disease itself.”
He noted the LMRI model demonstrates how private philanthropy can play a crucial role in addressing unmet medical needs. In this case, nearly all of the work has been supported by a single family.
Reference
Neurotech’s ENCELTO (revakinagene taroretcel-lwey) approved by the FDA for the treatment of macular telangiectasia type 2 (MacTel). Press release. Neurotech Pharmaceuticals. Published March 6, 2025. Accessed March 6, 2025. https://www.neurotechpharmaceuticals.com/neurotechs-enceltotm-revakinagene-taroretcel-lwey-approved-by-the-fda-for-the-treatment-of-macular-telangiectasia-type-2-mactel/
