Abstract
PURPOSE: To evaluate the impact of modifying the abicipar pegol (abicipar) manufacturing process on the safety and treatment effect of abicipar in patients with neovascular age-related macular degeneration (nAMD).
METHODS: A new process for manufacturing abicipar was developed to reduce host cell impurities. In a prospective, Phase 2, multicenter, open-label, 28-week clinical trial, patients (n=123) with active nAMD received intravitreal injections of abicipar 2 mg at baseline (day 1) and weeks 4, 8, 16, and 24. Outcome measures included proportion of patients with stable vision (<15-letter loss from baseline; primary endpoint), change from baseline in best-corrected visual acuity (BCVA) and central retinal thickness (CRT), and adverse events.
RESULTS: Overall, 8.9% (11/123) of patients experienced intraocular inflammation (IOI) and discontinued treatment. IOI cases were assessed as mild (2.4% [3/123]), moderate (4.9% [6/123]), or severe (1.6% [2/123]) and resolved with steroid treatment. Visual acuity in most patients with IOI (8 of 11) recovered to baseline BCVA or better by study end. No cases of endophthalmitis or retinal vasculitis were reported. Stable vision was maintained for ≥95.9% (≥118/123) of patients at all study visits. At week 28, treatment-naïve patients showed a greater mean improvement from baseline in BCVA compared with previously treated patients (4.4 vs 1.8 letters) and a larger mean CRT reduction from baseline (98.5 vs 45.5 μm).
CONCLUSION: Abicipar produced using a modified manufacturing process showed a moderately lower incidence and severity of IOI compared with Phase 3 abicipar studies. Beneficial effects of treatment were demonstrated.
Original language | English (US) |
---|---|
Pages (from-to) | 1367-1384 |
Number of pages | 18 |
Journal | Clinical Ophthalmology |
Volume | 17 |
DOIs | |
State | Published - 2023 |
Keywords
- abicipar
- age-related macular degeneration
- inflammation
ASJC Scopus subject areas
- Ophthalmology
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In: Clinical Ophthalmology, Vol. 17, 2023, p. 1367-1384.
Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Impact of Modifying Abicipar Manufacturing Process in Patients with Neovascular Age-Related Macular Degeneration
T2 - MAPLE Study Results
AU - Callanan, David
AU - Khurana, Rahul N.
AU - Maturi, Raj K.
AU - Patel, Sunil
AU - Wykoff, Charles C.
AU - Eichenbaum, David
AU - Khanani, Arshad M.
AU - Hassan, Tarek
AU - Badger, Hanh
AU - Mehta, Shraddha
AU - Le, Grace
AU - Attar, Mayssa
AU - Seal, Jennifer
AU - Li, Xiao Yan
N1 - Funding Information: This study was sponsored by Allergan plc (Dublin, Ireland; prior to acquisition by AbbVie Inc). Allergan/AbbVie participated in the design of the study, data management, data analysis, interpretation of the data, and preparation, review, and approval of the manuscript. Funding Information: David Callanan serves as a consultant for Allergan (an AbbVie company), Applied Genetic Technologies Corporation, EyePoint, Eyevensys, Graybug, Regenerative Patch Technologies, and Takeda; is on the Speaker’s Bureau for Allergan (an AbbVie company); has received research support from Aerie, Amgen, Diopsys, Eyevensys, Genentech/Roche, Gilead, Ionis, and Regeneron; and is an equity holder and employee of Aviceda Therapeutics. Rahul N. Khurana serves as a consultant for Apellis, Bausch + Lomb, Genentech, NGM Biopharmaceuticals, and Ophthea; and has received grant support from Apellis, Chengdu Kanghong, Clearside Biomedical, Eyepoint, Genentech, NGM Biopharmaceuticals, Ophthea, Oxurion, and RegenXBio. Raj Maturi serves as a consultant to and has received grants from Aerpio, AiViva, Allegro, Allergan (an AbbVie company), Allgenesis, Astellas, Boehringer Ingelheim, Clearside, Dutch Ophthalmic, Eli Lilly, Genentech, Gemini, GlaxoSmithKline, Graybug, Gyroscope, Jaeb Center for Health Research, Kalvista, NGM Biopharmaceuticals, Neurotech, Novartis, Ophthea, Oxurion, Ribomic, Roche, Samsung, Santen, Senju, ThromboGenics and Unity. Sunil Patel serves as a consultant for AiViva, Allergan (an AbbVie company), Allgenesis, Genentech-Roche, Kala, Kodiak Sciences; is on an advisory board for Allergan (an AbbVie company), Genentech-Roche, and Kodiak Sciences; has received research support from Aerie, Aerpio, Allergan, Allgenesis, Apellis, Boehringer Ingelheim, Chengdu Kanghong, Clearside, Eyepoint, Genentech-Roche, Ionis Pharmaceuticals, Iveric Bio, KalVista, Kodiak Sciences, Mylan, Novartis, Oculis, Opthea, Ophthotech, Ora, Oxurion, Regeneron, Samsung, SmileBiotek, Stealth Biotherapeutics, ThromboGenics, and Xbrane Biopharma; and has received personal fees from AiViva, Kala, Ocugenix, and RegenxBio, outside the submitted work; he is also the Chief Medical Officer and stock owner of Allgenesis Biotherapeutics, Inc. Charles C. Wykoff is a consultant for 4DMT, Adverum, Aerie Pharmaceuticals, AGTC, Alcon, Alimera, Allergan (an AbbVie company), Allgenesis, Alnylam, Annexon, Apellis, Arrowhead Pharmaceuticals, Bausch + Lomb, Bayer, Bionic Vision Technologies, Boehringer Ingelheim, Cholgene, Clearside, Curacle, Chengdu Kanghong Biotechnologies, Clearside Biomedical, EyePoint Pharmaceuticals, Foresite, Frontera, Genentech/Roche, Gyroscope, IACTA, Iveric Bio, Janssen, Kato Pharmaceuticals, Kiora, Kodiak Sciences, Kriya, Merck, Nanoscope, NGM Biopharmaceuticals, Notal Vision, Novartis, OccuRx, Ocular Therapeutix, Ocuterra, OliX, ONL Therapeutics, Opthea Limited, Oxurion, Palatin, PerceiveBio, Perfuse, PolyPhotonix, Ray, RecensMedical, Regeneron, Resonance, REGENXBIO, Roche, SAI MedPartners, SciNeuro, Stealth, Surrozen, Takeda, THEA, TissueGen, Valo, and Verana Health; has received research support from 4DMT, Adverum, Aerie Pharmaceuticals, Aldeyra, Aerpio, AffaMed, Alexion, Alimera Sciences, Alkahest, Allergan (an AbbVie company), Allgenesis, Amgen, Annexin, Annexon, Apellis, Arctic Vision, Asclepix, Bayer, Boehringer Ingelheim, Chengdu Kanghong Biotechnologies, Clearside Biomedical, EyePoint, Gemini Therapeutics, Genentech/Roche, GlaxoSmithKline, Graybug Vision, Gyroscope, IONIS Pharmaceuticals, iRENIX, Iveric Bio, Kodiak Sciences, LMRI, Nanoscope, Neurotech Pharmaceuticals, NGM Biopharmaceuticals, Novartis, Ocular Therapeutix, Ocuphire, OcuTerra, Ophthotech, Opthea, Outlook Therapeutics, Oxurion, Oxular, Oyster Point, PerceiveBio, RecensMedical, Regeneron, REGENXBIO, Roche, SamChunDang Pharm, Sandoz, Senju, Taiwan Liposome Company, UNITY, Verily, and Xbrane BioPharma; and has stock options for ONL Therapeutics, PolyPhotonix, RecensMedical, TissueGen, and Visgenx. David Eichenbaum is a consultant for Alimera Sciences, Allergan (an AbbVie company), Apellis, Bausch + Lomb, Coherus, Crinetics, the Dutch Ophthalmic Research Center, EyePoint, Genentech, Gyroscope Therapeutics Limited, Iveric Bio, KKR, Kodiak Sciences, Novartis, Ocular Therapeutix, Opthea, Outlook, RecensMedical, Regeneron, Regenxbio, ReVive, US Retina, and Vial; has served as an investigator for 4DMT, Alexion, Alkahest, Allegenesis, Annexon, AsclepiX, Bayer, Chengdu Kanghong Biotechnologies, EyePoint, Gemini, Genentech, Gyroscope Therapeutics Limited, Ionis, Iveric Bio, Kodiak Sciences, Mylan, NGM Biopharmaceuticals, Novartis, Ocular Therapeutics, Opthea, RecensMedical, Regeneron, Regenxbio, and Unity; has received speaker fees from Allergan (an AbbVie company), Apellis, Bausch + Lomb, Bayer, the Dutch Ophthalmic Research Center, EyePoint, Genentech, and Novartis; has received personal fees from Alimera and Samsama; has received grants from 4DMT, Alexion, Alkahest, Allegenesis, Annexon, AsclepiX, Aviceda, Chengdu, EyePoint, Gemini, Genentech, Gyroscope, Ionis, IvericBio, Kodiak, Mylan, NGM, Novartis, Ocular Therapeutix, Opthea, RecensMedical, Regeneron, RegenxBio, and Unity, outside the submitted work; holds equity and/or stocks for Boston Image Reading Center, Clearside Biomedical, Hemera Biopharmaceuticals, Network Eye, ReVive, and US Retina; and founded Network Eye. Arshad Khanani is a consultant for Adverum, Aerpio, Allergan (an AbbVie company), Chengdu Kanghong, DORC International, Genentech, Kato, Kodiak, Novartis, Gemini Therapeutics, Gyroscope, Iveric Bio, Opthea, Oxurion, RecensMedical, Regenxbio, and Roche; has received research support from Adverum, Allergan (an AbbVie company), Chengdu Kanghong, Gemini Therapeutics, Genentech, Gyroscope, Iveric Bio, Kodiak, NGM Bio, Novartis, Opthea, Oxurion, RecensMedical, Regenxbio, and Roche; and has received speaker fees from Allergan (an AbbVie company) and Novartis. Tarek Hassan is a consultant for Allergan (an AbbVie company), Aviceda, Bayer, EyePoint, Genentech, Iveric Bio, Novartis, Regeneron, and Roche. Hanh Badger, Shraddha Mehta, Grace Le, and Xiao-Yan Li were employees of Allergan plc at the time of the study. Mayssa Attar and Jennifer Seal are employees of AbbVie and may hold stock/stock options. The authors report no other conflicts of interest in this work. Funding Information: AbbVie and the authors thank the investigators and patients who participated in the MAPLE study, and Dr Swati Gupta (AbbVie) and Dr Joe Zhou (former employee of Allergan) for conducting the in vitro PBMC studies. Nayna Sanathara, PhD, of AbbVie Inc., provided medical writing assistance for the development of this publication. Editorial support was provided by Evidence Scientific Solutions, Inc. (Philadelphia, PA) and funded by AbbVie. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. DARPin is a registered trademark of Molecular Partners (Zurich, Switzerland). Publisher Copyright: © 2023 Callanan et al.
PY - 2023
Y1 - 2023
N2 - PURPOSE: To evaluate the impact of modifying the abicipar pegol (abicipar) manufacturing process on the safety and treatment effect of abicipar in patients with neovascular age-related macular degeneration (nAMD).METHODS: A new process for manufacturing abicipar was developed to reduce host cell impurities. In a prospective, Phase 2, multicenter, open-label, 28-week clinical trial, patients (n=123) with active nAMD received intravitreal injections of abicipar 2 mg at baseline (day 1) and weeks 4, 8, 16, and 24. Outcome measures included proportion of patients with stable vision (<15-letter loss from baseline; primary endpoint), change from baseline in best-corrected visual acuity (BCVA) and central retinal thickness (CRT), and adverse events.RESULTS: Overall, 8.9% (11/123) of patients experienced intraocular inflammation (IOI) and discontinued treatment. IOI cases were assessed as mild (2.4% [3/123]), moderate (4.9% [6/123]), or severe (1.6% [2/123]) and resolved with steroid treatment. Visual acuity in most patients with IOI (8 of 11) recovered to baseline BCVA or better by study end. No cases of endophthalmitis or retinal vasculitis were reported. Stable vision was maintained for ≥95.9% (≥118/123) of patients at all study visits. At week 28, treatment-naïve patients showed a greater mean improvement from baseline in BCVA compared with previously treated patients (4.4 vs 1.8 letters) and a larger mean CRT reduction from baseline (98.5 vs 45.5 μm).CONCLUSION: Abicipar produced using a modified manufacturing process showed a moderately lower incidence and severity of IOI compared with Phase 3 abicipar studies. Beneficial effects of treatment were demonstrated.
AB - PURPOSE: To evaluate the impact of modifying the abicipar pegol (abicipar) manufacturing process on the safety and treatment effect of abicipar in patients with neovascular age-related macular degeneration (nAMD).METHODS: A new process for manufacturing abicipar was developed to reduce host cell impurities. In a prospective, Phase 2, multicenter, open-label, 28-week clinical trial, patients (n=123) with active nAMD received intravitreal injections of abicipar 2 mg at baseline (day 1) and weeks 4, 8, 16, and 24. Outcome measures included proportion of patients with stable vision (<15-letter loss from baseline; primary endpoint), change from baseline in best-corrected visual acuity (BCVA) and central retinal thickness (CRT), and adverse events.RESULTS: Overall, 8.9% (11/123) of patients experienced intraocular inflammation (IOI) and discontinued treatment. IOI cases were assessed as mild (2.4% [3/123]), moderate (4.9% [6/123]), or severe (1.6% [2/123]) and resolved with steroid treatment. Visual acuity in most patients with IOI (8 of 11) recovered to baseline BCVA or better by study end. No cases of endophthalmitis or retinal vasculitis were reported. Stable vision was maintained for ≥95.9% (≥118/123) of patients at all study visits. At week 28, treatment-naïve patients showed a greater mean improvement from baseline in BCVA compared with previously treated patients (4.4 vs 1.8 letters) and a larger mean CRT reduction from baseline (98.5 vs 45.5 μm).CONCLUSION: Abicipar produced using a modified manufacturing process showed a moderately lower incidence and severity of IOI compared with Phase 3 abicipar studies. Beneficial effects of treatment were demonstrated.
KW - abicipar
KW - age-related macular degeneration
KW - inflammation
UR - http://www.scopus.com/inward/record.url?scp=85160233062&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85160233062&partnerID=8YFLogxK
U2 - 10.2147/OPTH.S405994
DO - 10.2147/OPTH.S405994
M3 - Article
C2 - 37197577
AN - SCOPUS:85160233062
SN - 1177-5467
VL - 17
SP - 1367
EP - 1384
JO - Clinical Ophthalmology
JF - Clinical Ophthalmology
ER -