Retinal diseases refer to any damage to the retina, the back part of the eye that contains millions of light-sensitive cells responsible for receiving, organizing, and sending visual information to the brain. Since the retina is the one that enables us to see, retinal diseases that are left untreated may lead to vision loss or blindness.
According to the National Eye Institute, the estimated number of people suffering from age-related macular degeneration (AMD), the most common retinal disease and the major cause of irreversible blindness in adults aged 60 and older, will more than double from 2.1 million in 2010 to 5.4 million in 2050. Together with diabetic macular edema (DME), the second most common blind-causing retinal disease, there are a total of 4 million individuals actively affected. For more information on retinal diseases, check Retinal Vascular Diseases.
By detecting early, an eye doctor can provide appropriate treatment to control retinal damage or even preserve or restore vision. Depending on the type of retinal disorder and the extent of the damage, treatment options vary from medications and vitamins to injections, laser treatments, and surgery.
AMD and DME are typically treated by injecting Vascular Endothelial Growth Factor (VEGF) inhibitors intravitreal or in the gel-like part of the eye. VEGF inhibitors are agents that impede the signaling activity of tyrosine kinase receptors VEGR and VEGFR. These receptors modulate angiogenesis or the process of making new blood vessels from existing blood vessels.
Although this treatment helps improve vision by reducing leakiness of eye blood vessels, certain drawbacks made adherence and widespread adoption of the treatment a great challenge. Injection of VEGF inhibitors is typically required every four to twelve weeks in an often indefinite period. This makes it a substantial burden to some patients, caregivers, and eye care providers, leading to under-treatment.
This problem pushed researchers to discover new molecules that might allow more prolonged treatment intervals. In January 2022, the U.S. Food and Drug Administration (FDA) recently approved intravitreal faricimab, a bispecific antibody drug, to treat both retinal diseases. The approval of faricimab brings in a promising retinal disease treatment with a triple effect—inhibition of the disease processes of AMD and DME, visual acuity improvement, and lowered patient treatment burden.
Mechanism of action
The current VEGF inhibitors like aflibercept that are used as a first-line of retinal treatment option block only the VEGF pathway. Vabysmo, the first faricimab drug manufactured by Genentech, acts through dual inhibition. This means that this new drug blocks not only the VEGF pathway but also the angiopoietin-2 (Ang-2) pathway. The Ang-2 can bind to tyrosine kinase(Tie-2) endothelial receptors to regulate blood vessel formation.
These two pathways are thought to be responsible for destabilizing blood vessels that lead to vision loss. Therefore, inhibiting them through faricimab stabilizes the blood vessels and subsequently decreases inflammation and leaking.
Clinical studies supporting the effectiveness of intravitreal faricimab
Vabysmo received FDA approval after the successful results of the four large phase III clinical trials that investigated the efficacy, safety, and durability of Vabysmo compared to aflibercept.
These four trials included TENAYA and LUCERNE studies for wet AMD and YOSEMITE and RHINE studies for DME. Randomized, multicenter, double-masked, and global, all four showed consistent positive treatment effects for AMD and DME patients.
The first four monthly doses of faricimab, administered at three to four months of intervals, had the same effects as that of aflibercept administered in a 2-month interval in terms of maintaining vision and reducing retinal fluid during the first treatment year. This means that patients will have less treatment burden while possibly improving visual acuity.
The TENAYA and LUCERNE studies included 1,329 patients with wet AMD. The results of the studies showed an increased visual acuity average of +5.8 and +6.6 letters for patients treated with 6.0-mg doses of faricimab during the one-year evaluation. Only +5.1 and +6.6 letters visual acuity average was observed for patients treated with 2.0-mg doses of aflibercept at fixed eight-week intervals.
In terms of treatment burden, the studies also showed a reduction of treatment burden where almost half of the patients—46% for TENAYA and 45% for LUCERNE—were treated at a 4-month interval during the first year. A third of the patients for both studies were also treated at a 3-month interval during the first year. These data indicated that most patients did not require frequent treatment for the first year.
Similarly, the YOSEMITE and RHINE studies, which included 1,891 patients with DME obtained visual acuity gain results non-inferior to aflibercept.
Now, extension studies of the same manufacturers are underway to evaluate the long-term safety and tolerability of faricimab in DME and wet AMD. Aside from this, they are also considering investigating the beneficial treatment effects of this medicine on other types of retinal diseases.
Administration and dosing
Faricimab is given as an intravitreal injection at a 6-mg dose from 0.05 mL of a 120 mg/mL solution. It facilitates various dosing regimens based on the patient’s visual anatomy and initial outcomes of the treatment.
In clinical practices, the dosing regimen for both AMD and DME begins with a series of four doses given every four weeks. This is followed by a personalized treatment schedule, where the same dose is administered from one to four months. For AMD patient, the subsequent treatments consist of the same dose injected every 2, 3, or 4 months depending on the results of coherence tomography and visual acuity evaluations. For DME patients, the subsequent treatments may be reduced or extended—with a range of 1 to 4 months between doses—depending also on the visual outcomes after the four initial monthly injections.
