New AMD therapies aim to reduce treatment burden
Age-related macular degeneration is one of the leading causes of vision loss in the elderly population. Although new treatments have been beneficial in reducing vision loss and slowing the disease, they often come with a difficult burden.
Most AMD treatments include intraocular injections of anti-vascular endothelial growth factor (VEGF) medicine, which are required monthly or bimonthly.
“The burden of coming to the clinic so frequently is very challenging for elderly patients who often rely on family members or caregivers for transportation,” Diana Do, MD, vice chair for clinical affairs and professor of ophthalmology at the Byers Eye Institute at Stanford University School of Medicine, told Healio in an email interview.
Clinical trials have shown anti-VEGF injections maintained visual acuity in more than 90% of patients; however, these results are not equaled in real-world practice, according to an article published in the American Journal of Managed Care.
“Results in clinical practice do not always measure up to those obtained in rigorous phase 3 trials,” Caroline R. Baumal, MD, professor of ophthalmology at Tufts University School of Medicine, wrote. “Undertreatment and the burden on patients and caregivers from frequent anti-VEGF injections contribute to suboptimal visual acuity results in the real world.”
Although the burden of treatment is high, it is necessary to keep up with the frequent visits to maintain the treatments’ efficacy.
“Wet AMD is a chronic condition that needs appropriate follow-up and treatment,” Do said. “Clearly, there remains an unmet need to develop novel biologics that can provide more durability of VEGF suppression within the eye.”
‘Promising’ new device
A new port Delivery System (PDS, Genentech), which is currently being studied in patients with AMD, could reduce this burden significantly.
The PDS device is implanted into the eye and is designed to release a customized formulation of ranibizumab 100 mg/mL over a period of 6 months. It then remains in the eye and is refilled through a self-sealing septum.
Data from the phase 3 ARCHWAY clinical trial showed eyes treated with the PDS implant gained an average 0.2 letters in visual acuity from baseline, according to Do. In addition, 98.4% of patients were able to go the full 6 months between treatments, with the study also showing that the PDS implant was noninferior to monthly ranibizumab injections.
“The ARCHWAY study provides evidence that the PDS is a promising new surgical device that can provide sustained VEGF inhibition,” Do said.
Despite the device’s promise, retina surgeons do need to be cognizant of certain safety issues. In early trials, there was an increased risk for post-operative hemorrhage in early trials, but surgical technique changes reduced that risk. Nevertheless, since the device stays in the eye, there are additional risks for endophthalmitis and conjunctival retraction.
“Careful attention to handling the conjunctiva and appropriately covering the implant at the conclusion of the surgery is necessary,” Do added.
It is also important to note that not every patient will be a candidate for the PDS device. Those who respond well to treat-and-extend anti-VEGF regimens, those with concomitant glaucoma who need surgical intervention and those with conjunctival disorders or conjunctival scarring would not warrant the PDS device, according to Do.
“Office-based therapies will still be a mainstay of treatment,” she said. “If a patient with wet AMD responds to intravitreal anti-VEGF medicines but requires high frequency treatment (monthly), then that patient may be a good candidate for the PDS.”
Novel therapies
Faricimab (Genentech) is another treatment option on the horizon.
A bispecific antibody, faricimab targets two pathways, angiopoietin-2 (Ang-2) and VEGF-A. Four phase 3 trials have shown positive results for faricimab in extending treatment duration for both AMD and diabetic macular edema.
Administered in 4-month intervals, the injection had noninferior vision gains compared with aflibercept (Eyelea, Regeneron) every 2 months.
The TENAYA and LUCERNE trials, which concerned faricimab in wet AMD, included 1,329 patients receiving 6 mg of the drug at 2, 3 or 4 months.
Average vision gains in the two trials were 5.8 and 6.6 letters from baseline, compared with 5.1 and 6.6 letters in the aflibercept arms, according to a Genentech press release.
“In addition, 45% of eyes treated with faricimab were able to be treated every 4 months in the first year [and] approximately 34% were able to be treated every 3 months in the first year,” Do said.
A very recent entry to the AMD treatment space is KSI-301. Another anti-VEGF agent, the investigational therapy from Kodiak Sciences is built on the company’s Antibody Biopolymer Conjugate (ABC) Platform and is designed to maintain effective drug levels in ocular tissues longer than existing treatments, according to a company press release.
“The year 1 data for KSI-301 in treatment-naive wet AMD patients demonstrated that 66% of eyes achieved a 6-month treatment-free interval,” Do said. “Furthermore, 78% of patients were on a 4-month or longer interval.”
Study data also showed 54% of patients with wet AMD required only one retreatment in the first year after receiving three loading doses of KSI-301.
“It’s very exciting to be in the field of retina and to continue developing novel medicines for our patients,” Do said. “I’m confident we will have more effective therapies for our wet AMD patients in the near future.”
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Baumal C. Am J Manag Care. 2020;doi:10.37765/ajmc.2020.43435.
Genentech press release
Kodiak press release
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