Genentech, Inc., a member of the Roche Group, reported positive topline findings from the phase 4 ELEVATUM trial evaluating VABYSMO (faricimab-svoa) for treating diabetic macular edema (DME) among a specific subset of patients: underrepresented racial and ethnic groups.
The data was presented earlier this month during the American Academy of Ophthalmology (AAO) annual meeting in Chicago, Illinois.
Let’s start with Vabysmo.
The FDA-approved VABYSMO [va-bis-mo] is the first bispecific antibody indicated for neovascular (wet) age-related macular degeneration (AMD) and DME via an intravitreal (IVT) injection.
To note: The therapeutic is also approved to treat macular edema following retinal vein occlusion (RVO) as well as in a Prefilled Syringe (PFS) version for all three indications.
- See here for Vabysmo’s recommended dosage based on indication.
And didn’t the company already release new findings on it?
Yes, in July 2024. However, that was based on 4-year data from a long-term extension study evaluating its efficacy for wet AMD.
Those findings: By the end of Year 4, nearly 80% of VABYSMO-treated had extended their treatment intervals to every 3 or 4 months—and 90% achieved DME absence.
Now to this phase 4 study.
The multicenter, open-label, single-arm study (NCT05224102) is enrolling a total of 124 patients (ages 18+) diagnosed with diabetes mellitus (type 1 or type 2) at 51 sites across the United States, India, Kenya, and Puerto Rico.
Among participants:
- 45% self-identified as Hispanic or Latino
- 48% self-identified as Black or African American
Also: Included in the participant criteria was no previous anti-vascular endothelial growth factor (VEGF) treatment prior to the study as well as a hemoglobin A1c (HbA1c) level of up to 12%.
- To note: Genentech noted that while the threshold for DME trials is an HbA1 level of 10%, these levels can be higher among the aforementioned participant demographics versus Caucasians.
Meaning: “A lower HbA1 threshold can inadvertently lead to the exclusion of patients from various ethnic and racial groups,” the company stated.
Gotcha. And how is the study designed?
Patients are randomized 1:1 to receive VABYSMO (6 mg) IVT every 4 weeks (Q4W) up to Week 20, followed by treatment every 8 weeks (Q8W)up to Week 56 (safety follow-up visit).
Note: For eligible participants who opt to continue into the long-term extension (LTE) phase of the study, VABYSMO injections will be given based on a personalized treatment interval (PTI) dosing algorithm (with Q4W at a minimum and every 24 weeks at a maximum).
What’s being measured?
The primary outcome measures include:
- In the main phase:
- Best-corrected visual acuity (BCVA) from baseline to Week 56
- In the LTE phase:
- Ocular adverse events (AEs), measured from Day 1 to end of LTE (up to 100 weeks)
- Non-ocular AEs, measured from Day 1 to end of LTE (up to 100 weeks)
While secondary outcomes include:
- In the main phase:
- Participants with ≥ 2-step Early Treatment Diabetic Retinopathy Scale (ETDRS) Diabetic Retinopathy Severity Scale (DRSS) improvement from baseline to Week 20 and 56
- Participants with ≥ 3-step ETDRS DRSS improvement from baseline to Week 20 and 56
- Change from baseline in central subfield thickness (CST) over time, as measured at baseline and Weeks 4, 8, 12, 16, 20, 28, 36, 44, 48, 52, and 56
At long last: Talk about this topline data.
Genentech reported that after 1 year of VABYSMO treatment (Q8W): “Participants could read an additional 12.3 letters on average—equivalent to about 2.5 lines on an eye chart.”
The company added that findings among the study’s major racial and ethnic groups represented were “similar,” with Hispanic and Latino participants starting the study with the most severe disease (equal to 3 lines on an eye chart).
And their average vision gain?
At 1 year, their average gain was 14.1 letters from baseline, “equivalent to nearly 3 lines on an eye chart.”
How did Black and African American participants perform?
This group gained an average of 11.3 letters from baseline at 1 year.
And Vabysmo’s safety profile?
In all, the therapeutic was found to be “well tolerated, with no new safety events identified.”
Nice! So how did this data compare to previous DME findings?
The company reported the findings to be consistent with those observed in both phase 3 YOSEMITE (NCT03622580) and RHINE studies (NCT03622580).
Case in point: One of the phase 4 trial’s secondary endpoints demonstrated “robust retinal drying with VABYSMO” across the aforementioned racial and ethnic groups—who, per Genentech, “on average, achieved a decrease of 206.3 μm in (CST) from baseline.”
- Keep in mind: Reduced CST is indicative of retinal drying.
- Why this is important: Swelling from too much fluid in the retina can lead to distorted/blurred vision.
Now, I have to ask: Why focus on these patient populations?
Vabysmo has already demonstrated its efficacy as a first-line treatment for DME, Genentech stated.
However: Certain ethnic and racial groups are notably “disproportionately affected” by the retinal disease “and lag far behind in clinical trial representation,” according to Genentech’s Gregory A. Rippon, MD, MS, vice president of U.S. Medical Affairs.
- As such: This new study is the first retinal trial for historically underrepresented populations.
“We conducted the ELEVATUM study to specifically address this issue and understand how underrepresented patient populations respond to treatment with Vabysmo,” stated Dr. Rippon, to help deliver better, more equitable care, and change how clinical trials are designed in the future.”
And what does this mean for the future?
Genentech’s VP and Chief Diversity Officer Quita Highsmith noted that the company is “challenging the status quo and pioneering a new era of inclusive research” that targets long-standing health disparities.
Highsmith added: “The ELEVATUM study is a significant milestone that not only establishes a blueprint of best practices to enroll more diverse patients, but confirms our continued commitment to advancing inclusive research for all patients.”