In new research published in JAMA Ophthalmology, investigators evaluated the effect of 1 year of repeated 0.1-mL intravitreous injections of lampalizumab on intraocular pressure (IOP) outcomes.
Give me some background first.
Neurovascular (wet) age-related macular degeneration (nAMD) is a late form of AMD, an eye disease that can blur the central vision.
Frequent intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections are a first-line therapy used for nAMD.
Now on to lampalizumab.
The study authors define lampalizumab as, “an antigen-binding fragment of a humanized monoclonal antibody that inhibits complement factor D [CFD].”
It was developed by Genentech to be a potential treatment for geographic atrophy (GA) secondary to AMD.
Go on …
However: Genentech reported in 2017 that the company would not pursue approval from the FDA for lampalizumab in GA after findings from two phase 3 trials—SPECTRI (NCT02247531) and CHROMA (NCT02247479) did not meet their primary endpoints.
- Those endpoints:
- Change from baseline in GA area
- Change from baseline in GA area in CFI positive and negative participants
So why investigate lampalizumab now?
In a previous study, patients who received 0.05-mL intravitreous anti-VEGF injections of ranibizumab, bevacizumab, pegaptanib, and triamcinolone acetonide demonstrated acute increases in IOP.
This led the authors to investigate the impact of 0.1-mL intravitreous injections of lampalizumab on IOP.
Now, talk about the study.
A post-hoc analysis of two clinical trials was conducted between 2018 and 2022.
The clinical trials themselves were previously conducted between 2014 and 2018 and investigated the IOP safety of intravitreous lampalizumab on GA secondary to AMD.
These trials were:
- CHROMA (NCT02247479)
- SPECTRI (NCT02247531)
Give me a quick overview of CHROMA and SPECTRI.
These phase 3 trials in GA were:
- Identical
- Global
- Randomized
- Double-masked
- Sham injection–controlled
Now to this later study; let’s talk participants.
Participants were recruited from both of these trials, with inclusion criteria consisting of patients aged 50+ with bilateral GA—among other criteria.
And how was itconducted?
During the trials, participants were randomly assigned in a 2:1:2:1 ratio to receive:
- Lampalizumab, 10 mg/0.1 mL, intravitreous injection every 4 weeks
- Sham procedure every 4 weeks
- Lampalizumab, 10 mg/0.1 mL, every 6 weeks
- Sham procedure every 6 weeks
What about the main outcomes and measures?
These included:
- IOP changes in the 4-week-frequency study arms
- Ocular adverse events (AEs) to Week 48 in all arms
Findings?
Among the 1,851 participants, there was no change in mean pre-injection IOP values in either arm during the trial period.
Glaucoma and ocular hypertension AEs were reported in:
- 1.8% of participants treated with lampalizumab
- 1.6% of those in the sham arm
Limitations?
The method of measuring IOP was not protocol-specified. Additionally, the study did not use a placebo (instead, the investigators used sham treatment).
Ocular axial length was not measured and scleral rigidity was not evaluated, which may have impacted the clinical interpretation of IOP changes.
For a full overview of the limitations, see the study.
Expert opinion?
The authors stated, “These results may be valuable in the design of future therapeutic trials considering this volume for injections particularly as more recently approved agents use volumes of 0.07 to 0.1 mL.”
Take home.
These findings show that 0.1-mL intravitreous injections of lampalizumab may have a low risk of persistent ocular IOP alterations.