A principal investigator of a Phase IV postmarket study of Vabysmo (faricimab) in patients who have diabetic macular edema says the study aims to determine if the drug works as well in underrepresented minorities as it did in Phase III clinical trials that led to its approval by the Food and Drug Administration earlier this year.
“With this study, our goal is to see if we can improve our scientific understanding of diabetic macular edema and to improve the standard of care for all patients, not just the patients that were in the majority in previous DME clinical trials,” Matthew A. Cunningham, MD, a principal study investigator at his practice, Florida Retina Institute in Orlando, tells
The FDA approved intravitreal Vabysmo (Genentech/Roche) for DME based on results of the
YOSEMITE and RHINE trials.1 However, Dr. Cunningham notes, the percentage of minority populations in those trials, similar to previous DME trials, “was not representative of the population at large.”
The Phase IV trial, known as Elevatum (NCT05224102), will enroll around 120 patients in the United States and globally. Eligible patients must self-identify as Black/African American, Hispanic/Latino, Native American, Native Alaskan, Native Hawaiian or Pacific Islander. They must have active DME and be treatment-naive.
A study of national databases in 2017 reported the incidence of type 2 diabetes is 9 percent in Asians, 13.2 percent in African Americans, 12.8 percent in Hispanics and 7.6 percent in non-Hispanic Whites.2 In the Native American population, incidence ranged from 6 percent in Alaskan Natives to 24.1 percent in southern Arizona Native American groups. Subgroups within those identifying as Hispanic also had wide disparities, ranging from 8.5 percent in Central/South Americans to 14.8 percent in those identifying as Puerto Rican.
“Within our underrepresented patient population, we know that this population is disproportionately affected by diabetes and, as a whole they are at a higher risk of developing diabetic macular edema,” Dr. Cunningham says. “There’s an historical lack of diversity in clinical trials in ophthalmology and Elevatum, to my best knowledge, is the first industry-sponsored trial to attempt to address this, specifically looking in the DME space.”
Elevatum is a multicenter, open-label, single-arm trial in which the first patient was recently dosed. The primary endpoint is change from baseline in best corrected visual acuity at week 56, as measured on the Early Treatment Diabetic Retinopathy Study chart.
Secondary endpoints include safety, the percentage of patients who achieve at least two- and three-step improvement from baseline in the ETDRS Diabetic Retinopathy Severity Scale at weeks 20 and 56, and the percentage with absence of intraretinal fluid over time. Other key secondary endpoints are changes in subretinal fluid and central subfield thickness, BCVA improvement and levels of anti-drug antibodies against Vabysmo. Results are expected in 2024.
Elevatum is using criteria for hemoglobin A1c that’s broader than typical studies in diabetes, Dr. Cunningham adds. “Many studies won’t include patients because their HbA1c is greater than 10 percent,” he says. “In Elevatum that’s been broadened so that in up to 20 percent of participants, A1c may be up to 12 percent. That will hopefully ease one of the known barriers for clinical trial participation in this population.”
He notes that his site is participating because it has a higher proportion of underserved patients than the typical retina practice. The study offers participants compensation, meal stipends and assistance with transportation. “We’re trying to address some of these issues to give the patient one less thing to think about when it comes to being included or enrolled in the study,” Dr. Cunningham says.
Dr. Cunningham is a paid consultant for Genentech/Roche, as well as Alimera Sciences and Allergan/
— Richard Mark Kirkner
1. Wykoff CC, Abreau F, Adamis AP, et al. Efficacy, durability, and safety of intravitreal faricimab with extended dosing up to every 16 weeks in patients with diabetic macular oedema (YOSEMITE and RHINE): Two randomised, double-masked, phase 3 trials. Lancet. 2022:399:741-755.2. Ferdinand KC, Nasser SA. Racial/ethnic disparities in prevalence and care of patients with type 2 diabetes mellitus. Curr Med Res Opin 2015;31:913–923
RPE patch shows survivability after two years
An allogeneic retinal pigment cell transplant developed to treat severe vision loss from geographic atrophy has been shown to survive after two years without signs of inflammation or immune rejection, according to a recent paper in the journal Stem Cell Reports.1
In earlier results from the Phase I/IIa trial, the transplantable patch, known as CPCB-RPE1 (Regenerative Patch Technologies), was shown to be safe and well-tolerated out to a year.2
CPCB-RPE1 is a bioengineered implant consisting of stem cell-derived, mature, polarized retinal pigment epithelial cells on a synthetic parylene membrane. It’s placed in a subretinal bleb overlying the area of GA to replace damaged RPE and Bruch’s membrane.
In the most recent study, researchers evaluated the implant in the eye of an 84-year-old patient who died from pneumonia two years after receiving the implant. Postmortem histology confirmed that the cells on the transplant patch had survived, that they hadn’t migrated and were oriented in the optimal polarized position. Mohamed Faynus, a graduate student researcher in the laboratory of stem cell biologist Dennis O. Clegg, PhD, at the University of California Santa Barbara, says that provides evidence the cells maintained functionality.
The researchers also found that after two years, the patch hadn’t triggered neovascularization or scarring that could cause a retinal detachment. They also found no clinical sign of the inflammation that would indicate an immune response to the foreign cells, even after the patient was taken off immunosuppressants two months post-implantation.
“This is the first study of its kind and it indicates that the implanted RPE cells can survive and function, even in what could be a toxic environment of a diseased eye,” Dr. Clegg says.
Dr. Clegg holds equity in and is a consultant to Regenerative Patch Technologies.
1. Kashani AH, Lebkowski JS, Hinton DR, et al. Survival of an HLA-mismatched, bioengineered RPE implant in dry age-related macular degeneration. Stem Cell Rep. 2022;17:448-458.
2. Kashani AH, Lebkowski JS, Rahhal FM, et al. A bioengineered retinal pigment epithelial monolayer for advanced, dry age-related macular degeneration. Sci Transl Med. 2018;10:eaao4097.
Prevent Blindness and Regeneron Pharmaceuticals have partnered to expand their “Diabetes and the Eyes” education program to include a video series for both English and Spanish speakers, community-level health education and support, and new materials about how the disease impacts vision.
A clinical trial of photobiomodulation to treat dry age-related macular degeneration has shown a mean increase of 5.5 letters in 91 treated eyes after 13 months. The LIGHTSITE III prospective trial is evaluating the Valeda light delivery system (LumiThera). The results were presented at the 2022 Sonoma Eye Meeting.
Apellis Pharmaceuticals reports that 18-month results from the Phase III DERBY and OAKS trials of intravitreal pegcetacoplan show continued reduction in geographic atrophy lesion growth. Apellis says it will submit a New Drug Application to the Food and Drug Administration by summer.