NGM621 for geographic atrophy well tolerated in phase 1 study
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Results from a phase 1 first-in-human study evaluating NGM621, an anti-complement C3 antibody, in geographic atrophy secondary to age-related macular degeneration showed the therapy was safe and well tolerated.
“NGM621 was well tolerated up to 15 mg dosed twice in this phase 1 study with no safety signals, supporting the continued clinical development of NGM621,” Charles C. Wykoff, MD, PhD, said at the virtual Angiogenesis, Exudation, and Degeneration meeting.
The novel monoclonal antibody potently inhibits C3 and prevents downstream activation of the complement cascade. The primary objective of the study was to evaluate the safety and tolerability of single and multiple intravitreal injections of NGM621 (NGM Biopharmaceuticals) in patients with geographic atrophy secondary to AMD. Additionally, researchers attempted to characterize the pharmacokinetic (PK) and pharmacodynamic (PD) profile of the antibody, Wykoff said.
The study included three single-ascending dose cohorts of three patients receiving 2 mg per eye, three patients receiving 7.5 mg per eye and three patients receiving 15 mg per eye. One multidose cohort of six patients receiving 15 mg per eye given twice at 4 weeks apart was also included. All patients were dosed sequentially and followed for 12 weeks, he said.
At baseline, the average age was 78.6 years, visual acuity was approximately 20/250, and the mean geographic lesion area was 14.9 mm².
No safety or tolerability signals were observed in any cohort, with no safety events attributed to the drug, no endophthalmitis cases, no deaths, no intraocular inflammation cases, no vision-related safety signals and no cases of choroidal neovascularization development through the 12-week endpoint. On average, patients maintained their visual acuity as well, Wykoff said.
The serum PK profile of NGM621 following intravitreal injection was linear and dose proportional with low accumulation after a second dose 4 weeks apart, he said.
“Following intravitreal administration, NGM621 serum exposure was below concentrations that produce systemic complement inhibition. All subjects were ADA negative at all time points. Cumulatively, PK/PD modeling supports a 15 mg dosing interval of up to 8 weeks,” Wykoff said.
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Wykoff C, et al. Geographic atrophy with NGM621: Phase 1 dose-escalation study results. Presented at: Angiogenesis, Exudation, and Degeneration meeting; Feb. 12, 2021 (virtual meeting).
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