This article is more than 5 years old. Information may no longer be current.
Anti-Ang2 combined with anti-VEGF improves visual acuity, central retinal thickness
Click Here to Manage Email Alerts
CHICAGO — Visual acuity and anatomical improvements were achieved at all dose levels of nesvacumab combined with aflibercept in patients with diabetic macular edema or neovascular age-related macular degeneration, according to a study presented here.
David M. Brown , MD, told colleagues at the American Academy of Ophthalmology meeting that observations in a preclinical model of chronic vascular leak showed that nesvacumab, an anti-Ang2 agent, combined with aflibercept, an anti-VEGF, increased duration of anti-leak action of aflibercept. The observation led to the hypothesis that the combined product could produce a greater therapeutic effect than inhibition of either VEGF or Ang2 alone.
David M. Brown
In the open-label dose-escalation phase 1 study of 20 patients, four patients each were assigned to a cohort of nesvacumab 0.5 mg and aflibercept 2 mg, nesvacumab 1 mg and aflibercept 2 mg, nesvacumab 3 mg and aflibercept 2 mg, nesvacumab 6 mg and aflibercept 2 mg, or nesvacumab 6 mg alone. Two patients in each cohort had AMD and two had DME. Drug was administered at baseline, 4 weeks and 8 weeks in a single 50 µL injection. After week 8, re-treatment was reassessed.
“You basically got a dose if you were 50 µm greater than your lowest CRT (central retinal thickness), you had new or persistent cysts, you had a loss of five letters with any increase in CRT, or your BCVA increased by five letters,” Brown said.
Regarding side effects, one of the primary outcomes in a phase 1 study, Brown said there were no ocular adverse events in the highest dose; one patient had a myocardial infarction, which was not thought to be related to the therapy.
“For the safety, there were no dose-limiting toxicities, no intraocular inflammation, and it looked like we didn’t see any unexpected systemic or intraocular events. The one heart attack, we think, was unrelated,” Brown said. “In summary, this phase 1 AMD/DME study shows that nesvacumab/aflibercept is well tolerated. Visual acuity and anatomical improvements at all dose levels and extended duration are encouraging. And, consistent with the preclinical data, the efficacy and safety data led Regeneron to continue to phase 2 studies for AMD and DME.”
The RUBY trial, with 300 patients, is already fully enrolled, and the ONYX trial, with 360 patients, is enrolling. – by Patricia Nale, ELS
Reference:
Brown DM. Phase 1 study of combination therapy with nesvacumab and aflibercept for neovascular AMD and diabetic macular edema. Presented at: American Academy of Ophthalmology annual meeting; Oct. 14-18, 2016; Chicago.
Disclosure: Brown reports he has received research grant funding from Alcon/Novartis, Allergan, Clearside Biomedical, Genentech/Roche, NEI/NIH, Ophthotech, PRN, Regeneron/Bayer, Second Sight and ThromboGenics. He is a consultant for or is on the scientific advisory board of Adverum, Alcon/Novartis, Allergan, Carl Zeiss Meditec, Coda Therapeutics, Clearside Biomedical, Envisia, Janssen, Johnson & Johnson, Genentech/Roche, Heidelberg Engineering, Notal Vision, Ophthotech, Optos/Nikon, Optovue, Pfizer, Regeneron/Bayer, RegenxBio, Stealth Biotherapeutics and ThromboGenics.