Impact of Modifying Abicipar Manufacturing Process in Patients with Neovascular Age-Related Macular Degeneration: MAPLE Study Results

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.

Keywords:

• abicipar
• age-related macular degeneration
• inflammation

Abbreviations

Abicipar, abicipar pegol; AE, adverse event; BCVA, best-corrected visual acuity; BLQ, below the limit of quantification; CI, confidence interval; CNV, choroidal neovascularization; CRT, central retinal thickness; ETDRS, Early Treatment Diabetic Retinopathy Study; IIRMI, innate immune response modulating impurity; IL-1β, interleukin-1 beta; IL-6, interleukin 6; IOI, intraocular inflammation; IOP, intraocular pressure; LOCF, last observation carried forward; LPS, lipopolysaccharide; MedDRA, Medical Dictionary for Regulatory Activities; nAMD, neovascular age-related macular degeneration; PBMC, peripheral blood mononuclear cell; PBS, phosphate-buffered saline; PEG, polyethylene glycol; Q4, monthly; Q8, every 8 weeks following three loading doses; Q12, every 12 weeks following three loading doses; RPMI, Roswell Park Memorial Institute; SD-OCT, spectral-domain optical coherence tomography; TEAE, treatment-emergent adverse event; TNF-α, tumor necrosis factor-alpha; VEGF, vascular endothelial growth factor.

Data Sharing Statement

AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual, and trial-level data (analysis data sets), as well as other information (eg, protocols, clinical study reports, or analysis plans), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications. These clinical trial data can be requested by any qualified researchers who engage in rigorous, independent, scientific research, and will be provided following review and approval of a research proposal, Statistical Analysis Plan (SAP), and execution of a Data Sharing Agreement (DSA). Data requests can be submitted at any time after approval in the US and Europe and after acceptance of this manuscript for publication. The data will be accessible for 12 months, with possible extensions considered. For more information on the process or to submit a request, visit the following link: https://www.abbvieclinicaltrials.com/hcp/data-sharing/.html.

Acknowledgments

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).

This work was presented in part at the following congresses: American Society of Retina Specialists, July 30, 2019, Chicago, Illinois; Bascom Palmer Eye Institute – Angiogenesis, February 8, 2020, Miami, Florida; Macula Society, February 21, 2020, San Diego, California; Association for Research in Vision and Ophthalmology, June 4, 2020 (virtual meeting); and American Society of Retina Specialists, July 24, 2020 (virtual meeting).

Disclosure

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.

Additional information

Funding

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.