TY - JOUR
T1 - Inhibition of Complement Factor 3 in Geographic Atrophy with NGM621
T2 - Phase 1 Dose-Escalation Study Results
AU - Wykoff, Charles C.
AU - Hershberger, Vrinda
AU - Eichenbaum, David
AU - Henry, Erin
AU - Younis, Husam S.
AU - Chandra, Priya
AU - Yuan, Nancy
AU - Solloway, Mark
AU - DePaoli, Alex
N1 - Funding Information:
Funding/Support: NGM Biopharmaceuticals, Inc. Financial Disclosures: Charles C. Wykoff, Retina Consultants Texas. Disclosures: Acucela (C), Adverum (C, S), Aerie Pharmaceuticals (S), Aldeyra (S), Alimera Sciences (C), Allegro (C), Allergan (C), Apellis (C, S), Arctic Vision (C), Bausch and Lomb (C), Bayer (C), Chengdu Kanghong Biotechnologies (C, S), Clearside Biomedical (S), DORC (C), EyePoint (C), Gemini Therapeutics (S), Genentech (C, S), Graybug Vision (S), Gyroscope (C), IONIS Pharmaceutical (S), IVERIC Bio (C), Kodiak Sciences (C, S), LMRI (S), Merck (C), Neurotech Pharmaceuticals (S), NGM Biopharmaceuticals (C, S), Novartis (C, S), ONL Therapeutics (C), Opthea (C, S), Outlook Therapeutics (S), Oxurion (C), Palatin (C), Polyphotonix (C), Recens Medical (C, S), Regeneron (C, S), RegenXBio (C, S), Roche (C, S), Samsung Bioepis (S), Santen (S), Senju (S), Taiwan Liposome Company (S), Takeda (C), Thea Open Innovation (C), Xbrane BioPharma (S). Vrinda Hershberger, Florida Eye Associates. Disclosures: Genentech (C, S), Kodiak (C, S), NGM (S), Regeneron (C, S), Opthea (C, S). David Eichenbaum, Retina Vitreous Associates of Florida. Disclosures: Genentech (C, S, L), Regeneron (C, S), Allergan (C, S, L), Clearside (C, S, O), Novartis (C, S, L), Alimera (C, S), Ophthotech (S), Opthea (S), US Retina (O), Hemera Biopharmaceuticals (O), Boston Image Reading Center (O), Notal Vision (C), EyePoint (C, L), Mylan (S), Chengdu (S), Gyroscope (S, C), Kodiak (S, C), NGM (S), Network Eye (O), RecensMedical (C), DORC (C, L), Alkahest (S), Iveric Bio (S), Apellis (C). Alex DePaoli, Priya Chandra, Erin Henry, Husam S. Younis, Mark Solloway, and Nancy Yuan are employees of NGM Biopharmaceuticals. All authors attest that they meet the current ICMJE criteria for authorship. (C = Consultant/Advisor, L = Lecture fees; O = eEquity Owner; P = Patents/Royalty; S = Grant Support). Acknowledgements: The authors thank Charles Chen (NGM) and Rachel Hood (ApotheCom) for figure support, Frances E. Kane, PhD, for writing assistance, and Neang Ly, PhD, for pharmacokinetic analysis assistance. Data Sharing: The research data presented in this manuscript is confidential and proprietary to NGM Biopharmaceuticals, Inc. Prior Presentation: Some of the data included in the manuscript were presented at the American Academy of Ophthalmology 2020 Virtual Annual Meeting, November 13-15, 2020.
Publisher Copyright:
© 2021 The Authors
PY - 2022/3
Y1 - 2022/3
N2 - PURPOSE: To evaluate the safety and tolerability of single and multiple intravitreal injections of NGM621 in patients with geographic atrophy (GA) and to characterize the pharmacokinetics and immunogenic potential. DESIGN: Multicenter, open-label, single- and multiple-dose phase 1 study. METHODS: Fifteen patients enrolled at 4 sites in the United States. Participants had GA secondary to age-related macular degeneration, lesion size ≥2.5 mm2, best-corrected visual acuity of 4 to 54 letters (20/80 to 20/800 Snellen equivalent) in the study eye, and no history of choroidal neovascularization in either eye. Patients who met eligibility criteria were treated in a single ascending-dose phase (2 mg, 7.5 mg, and 15 mg) or received 2 doses of NGM621 (15 mg) 4 weeks apart in the multidose phase and were monitored for 12 weeks (85 days). Assessments included adverse events, best-corrected visual acuity, low-luminance visual acuity, vital signs, clinical laboratory evaluations, GA lesion area as measured by fundus autofluorescence, spectral domain optical coherence tomography, and pharmacokinetic, immunogenicity, and pharmacodynamic assessments. RESULTS: All 15 participants completed the 12-week study. There were no serious adverse events, no drug-related adverse events, and no choroidal neovascularization developed in either eye. Mean visual acuity and GA lesion area appeared stable through week 12 for all cohorts. Pharmacokinetic analyses indicated that NGM621 serum exposures appeared to be dose proportional, and no antidrug antibodies were identified at any of the evaluated time points. CONCLUSIONS: In this small, open-labeled, 12-week phase 1 study, NGM621 was safe and tolerable when administered intravitreally up to 15 mg.<END
AB - PURPOSE: To evaluate the safety and tolerability of single and multiple intravitreal injections of NGM621 in patients with geographic atrophy (GA) and to characterize the pharmacokinetics and immunogenic potential. DESIGN: Multicenter, open-label, single- and multiple-dose phase 1 study. METHODS: Fifteen patients enrolled at 4 sites in the United States. Participants had GA secondary to age-related macular degeneration, lesion size ≥2.5 mm2, best-corrected visual acuity of 4 to 54 letters (20/80 to 20/800 Snellen equivalent) in the study eye, and no history of choroidal neovascularization in either eye. Patients who met eligibility criteria were treated in a single ascending-dose phase (2 mg, 7.5 mg, and 15 mg) or received 2 doses of NGM621 (15 mg) 4 weeks apart in the multidose phase and were monitored for 12 weeks (85 days). Assessments included adverse events, best-corrected visual acuity, low-luminance visual acuity, vital signs, clinical laboratory evaluations, GA lesion area as measured by fundus autofluorescence, spectral domain optical coherence tomography, and pharmacokinetic, immunogenicity, and pharmacodynamic assessments. RESULTS: All 15 participants completed the 12-week study. There were no serious adverse events, no drug-related adverse events, and no choroidal neovascularization developed in either eye. Mean visual acuity and GA lesion area appeared stable through week 12 for all cohorts. Pharmacokinetic analyses indicated that NGM621 serum exposures appeared to be dose proportional, and no antidrug antibodies were identified at any of the evaluated time points. CONCLUSIONS: In this small, open-labeled, 12-week phase 1 study, NGM621 was safe and tolerable when administered intravitreally up to 15 mg.<END
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U2 - 10.1016/j.ajo.2021.08.018
DO - 10.1016/j.ajo.2021.08.018
M3 - Article
C2 - 34509438
AN - SCOPUS:85120605616
VL - 235
SP - 131
EP - 142
JO - American Journal of Ophthalmology
JF - American Journal of Ophthalmology
SN - 0002-9394
ER -