Low risk of elevated IOP with lampalizumab for geographic atrophy over 1 year

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Repeated 0.1-ml intravireal injections of lampalizumab (RG 7417, Genentech), antigen-binding fragment of a humanized monoclonal antibody that inhibits complement factor D,^1,2 seem to be associated with a low risk of elevated intraocular pressure (IOP) in patients with geographic atrophy (GA),³ according to Neil Bressler, MD, and colleagues. He is from Johns Hopkins University School of Medicine, Baltimore.

Historically, anti-vascular endothelial growth factor (VEGF) agents have been reported to cause IOP elevations that return to normal after about 30 minutes following 0.05-ml injections.⁴ However, the IOP elevations have become chronic in a small percentage of patients.^5,6

Bressler and colleagues pointed out that the more recently approved intravitreous agents are administered in volumes that exceed 0.05 ml, that is, from 0.07 to 0.1 mL, making IOP-related complications a concern.

In light of this, they conducted a post hoc analysis of data from 2 phase 3 clinical trials, CHROMA and SPECTRI⁷ (NCT02247479 and NCT02247531) to determine the effects of 1 year of repeated 0.1-mL intravitreous injections on the IOP outcomes following treatment for bilateral GA associated with age-related macular degeneration.

The patients received lampalizumab, 0.1 mL, every 4 weeks; lampalizumab, 0.1 mL, every 6 weeks; or sham procedure every 4 weeks or 6 weeks for 48 weeks, Bressler described.

The primary outcomes measures were the changes in the IOP in the patients treated every 4 weeks and the development of ocular adverse events out to week 48 in all study arms.

Post hoc analysis

The investigators reported that 1,851 patients were included. They found no change in the mean pre-injection IOP values through 48 weeks in either arm. In addition, glaucoma and ocular hypertension were reported for 1.8% of participants treated with lampalizumab and 1.6% of those in the sham arm.

The authors concluded, “Over 1 year, IOP increases were rare and did not affect treated participants more frequently than those in the sham arm. These findings support the low risk of persistent IOP increases, on average, of intravitreous 0.1-mL injection volumes administered for 1 year in a manner similar to that performed in these clinical trials. 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.”

References:

1. Loyet KM, Good J, Davancaze T, et al. Complement inhibition in cynomolgus monkeys by anti-factor d antigen-binding fragment for the treatment of an advanced form of dry age-related macular degeneration. J Pharmacol Exp Ther. 2014;35):527-537; doi:10.1124/jpet.114.215921

2. Holz FG, Sadda SR, Busbee B, et al; CHROMA and SPECTRI Study Investigators. Efficacy and safety of lampalizumab for geographic atrophy due to age-related macular degeneration: CHROMA and SPECTRI phase 3 randomized clinical trials. JAMA Ophthalmol. 2018;136:666-677; doi:10.1001/jamaophthalmol.2018.1544

3. Bressler NM, Freund KB, Bakri SJ, et al. Intraocular pressure outcomes after lampalizumab injections in patients with geographic atrophy. JAMA Ophthalmol. 2024; Published online June 20; doi:10.1001/jamaophthalmol.2024.2061

4. Kim JE, Mantravadi AV, Hur EY, Covert DJ. Short-term intraocular pressure changes immediately after intravitreal injections of anti-vascular endothelial growth factor agents. Am J Ophthalmol. 2008;146:930-4.e1. doi:10.1016/j.ajo.2008.07.007

5. Bakri SJ, Moshfeghi DM, Francom S, et al. Intraocular pressure in eyes receiving monthly ranibizumab in 2 pivotal age-related macular degeneration clinical trials. Ophthalmology. 2014;121:1102-1108; doi: 10.1016/j.ophtha.2013.11.029

6. Tseng JJ, Vance SK, Della Torre KE, et al. Sustained increased intraocular pressure related to intravitreal antivascular endothelial growth factor therapy for neovascular age-related macular degeneration. J Glaucoma. 2012;21:241-247; doi: 10.1097/IJG.0b013e31820d7d19

7. Holz FG, Sadda SR, Busbee B, et al; CHROMA and SPECTRI Study Investigators. Efficacy and safety of lampalizumab for geographic atrophy due to age-related macular degeneration: CHROMA and SPECTRI phase 3 randomized clinical trials.JAMA Ophthalmol. 2018;136:666-677; doi: 10.1001/jamaophthalmol.2018.1544