Hansjürgen Agostini1, Zufar Mulyukov2, Miltiadis Tsilimbaris3, Pilar Calvo4, Felicitas Bucher1, David Gaucher5, Etienne Pigeolet2, Valeria Colafrancesco6, Andreas Clemens2,7. 1. Eye Center, Medical Center, Faculty of Medicine, University of Freiburg , Freiburg, Germany. 2. Novartis Pharma AG , Basel, Switzerland. 3. Department of Ophthalmology, University Hospital of Heraklion , Heraklion, Greece. 4. IIS-Aragon, Department of Ophthalmology, Miguel Servet University Hospital , Zaragoza, Spain. 5. Nouvel Hôpital Civil, Hôpitaux Universitaires de Strasbourg , Strasbourg, France. 6. Novartis Farmaceutica, SA , Barcelona, Spain. 7. Department of Cardiology and Angiology I, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg , Freiburg, Germany.
Abstract
Aim: To compare the treatment effect of brolucizumab, a novel anti-vascular endothelial growth factor therapeutic, with a putative placebo in patients with wet age-related macular degeneration. Materials and Methods: Clinical treatment-effect data from patients receiving brolucizumab 6 mg in the HAWK and HARRIER studies were compared with modelled placebo data using a previously developed and validated indirect response, non-linear, mixed effects model describing the natural visual acuity decline in wet age-related macular degeneration. The placebo model incorporated patient-level data from the sham injection arms of the MARINA and PIER studies, corrected for baseline best corrected visual acuity and age difference between these studies and the HAWK and HARRIER studies. Results: Compared with a modelled placebo, brolucizumab treatment was associated with an overall best corrected visual acuity gain of approximately 22 Early Treatment Diabetic Retinopathy Study letters at Week 48 and 28 letters at Week 96. Conclusions: As anti-vascular endothelial growth factor therapy is now a standard of care for wet age-related macular degeneration, it is not feasible to conduct placebo-controlled trials for new wet age-related macular degeneration treatments. By allowing comparison with the natural decline in visual acuity without treatment, this analysis conveys the clinical importance of brolucizumab for the treatment of wet age-related macular degeneration.
Aim: To compare the treatment effect of brolucizumab, a novel anti-vascular endothelial growth factor therapeutic, with a putative placebo in patients with wet age-related macular degeneration. Materials and Methods: Clinical treatment-effect data from patients receiving brolucizumab 6 mg in the HAWK and HARRIER studies were compared with modelled placebo data using a previously developed and validated indirect response, non-linear, mixed effects model describing the natural visual acuity decline in wet age-related macular degeneration. The placebo model incorporated patient-level data from the sham injection arms of the MARINA and PIER studies, corrected for baseline best corrected visual acuity and age difference between these studies and the HAWK and HARRIER studies. Results: Compared with a modelled placebo, brolucizumab treatment was associated with an overall best corrected visual acuity gain of approximately 22 Early Treatment Diabetic Retinopathy Study letters at Week 48 and 28 letters at Week 96. Conclusions: As anti-vascular endothelial growth factor therapy is now a standard of care for wet age-related macular degeneration, it is not feasible to conduct placebo-controlled trials for new wet age-related macular degeneration treatments. By allowing comparison with the natural decline in visual acuity without treatment, this analysis conveys the clinical importance of brolucizumab for the treatment of wet age-related macular degeneration.
Authors: Andreas Clemens; Benjamin Gmeiner; Focke Ziemssen; Hansjürgen Agostini; Nicolas Feltgen; Robert P Finger; Christos Haritoglou; Hans Hoerauf; Matthias Iwersen; Martina Porstner Journal: Sci Rep Date: 2022-02-18 Impact factor: 4.379