Ranibizumab for Diabetic Macular Edema: Results from 2 Phase III Randomized Trials: RISE and RIDE

Optical coherence tomography angiography.

https://digitalcommons.unmc.edu/cgi/viewcontent.cgi?article=1047&context=com_eye_articles

Long-term outcomes of ranibizumab therapy for diabetic macular edema: the 36-month results from two phase III trials: RISE and RIDE.

The targeting of vascular endothelial growth factor A (VEGFA), a crucial regulator of both normal and pathological angiogenesis, has revealed innovative therapeutic approaches in oncology and ophthalmology. The first VEGFA inhibitor, bevacizumab, was approved by the US Food and Drug Administration in 2004 for the first-line treatment of metastatic colorectal cancer, and the first VEGFA inhibitors in ophthalmology, pegaptanib and ranibizumab, were approved in 2004 and 2006, respectively. To mark this tenth anniversary of anti-VEGFA therapy, we discuss the discovery of VEGFA, the successes and challenges in the development of VEGFA inhibitors and the impact of these agents on the treatment of cancers and ophthalmic diseases.

/pdf/ten-years-of-anti-vascular-endothelial-growth-factor-therapy-1grc0lcuq6.pdf

Ten years of anti-vascular endothelial growth factor therapy

The formation of the vascular network is an intricate and complex process that is an obligate requirement during vertebrate development. The cardiovascular system is the first organ to develop and reach a functional state, which underscores the crucial role of the vasculature in the developing embryo. The development of the vasculature into highly branched conduits needs to occur in numerous sites and in precise patterns to supply oxygen and nutrients to the rapidly expanding tissue of the embryo. This process is mediated by the coordinated response of vascular endothelial and mural cells to the heterogeneous angiogenic cues provided by tissues and organs, whereas aberrant regulation and coordination of angiogenic signals during development result in lethality, impaired organ development, or disease states. This article reviews the essential signaling pathways required for establishment of the vertebrate vasculature with a major focus on a key regulatory factor, vascular endothelial growth factor (VEGF). ...

Developmental and Pathological Angiogenesis

https://oftalmologiarafaelcaiado.files.wordpress.com/2012/04/cruise.pdf

Ranibizumab for macular edema following central retinal vein occlusion: six-month primary end point results of a phase III study.

Ranibizumab for Macular Edema following Branch Retinal Vein Occlusion

Sustained benefits from ranibizumab for macular edema following branch retinal vein occlusion: 12-month outcomes of a phase III study.

Complement C1q, the initiating molecule of the classical complement cascade, is involved in synapse elimination and neuronal loss in neurodegenerative diseases including glaucoma. Here we report an evaluation of the safety, tolerability, and ocular pharmacokinetics (PK) and pharmacodynamics of intravitreal (IVT) injections of ANX007, an anti-C1q monoclonal antibody fragment that blocks activation of the classical complement cascade.An open-label, single-dose-escalation phase Ia study followed by a double-masked, randomized, sham-controlled, repeat-injection phase Ib study.A total of 26 patients with primary open-angle glaucoma.Nine patients with primary open-angle glaucoma (mean Humphrey visual field deviation between -3 and -18 decibels [dB]) were enrolled in phase Ia and received single doses of ANX007 (1.0 mg, n = 3; 2.5 mg, n = 3; or 5.0 mg, n = 3). Seventeen patients (mean Humphrey visual field deviation between -3 and -24 dB) were enrolled in phase Ib and randomized to 2 monthly doses of ANX007 (sham, n = 6; 2.5 mg ANX007, n = 6; or 5 mg ANX007, n = 5).Safety and tolerability (including laboratory evaluation of urinalysis, complete blood count, and serum chemistries), ANX007 PK, target engagement, and immunogenicity.The mean age overall was 70 years in phase Ia and 68 years in phase Ib. In both studies, no serious adverse events were observed, no non-ocular treatment-emergent adverse events (TEAEs) attributable to study drug were reported, and ocular TEAEs were mild. Intraocular pressure returned to normal levels for all patients within 45 minutes of IVT injection. No clinically significant deviations in laboratory results were observed. In the phase Ib study, C1q in the aqueous humor was reduced to undetectable levels in both the 2.5 mg and 5 mg cohorts 4 weeks after the first ANX007 dose.In these studies, single and repeat IVT ANX007 injections were well tolerated and demonstrated full target engagement 4 weeks after dosing with both low and high doses, supporting monthly or less-frequent dosing. Further investigation in neurodegenerative ocular diseases is warranted.Proprietary or commercial disclosure may be found after the references. 

http://www.ophthalmologyscience.org/article/S2666914523000222/pdf

Wendy Yee Murahashi

Papers

Ranibizumab for macular edema following central retinal vein occlusion: six-month primary end point results of a phase III study.

Ranibizumab for Macular Edema following Branch Retinal Vein Occlusion

Sustained benefits from ranibizumab for macular edema following branch retinal vein occlusion: 12-month outcomes of a phase III study.

Safety and Target Engagement of Complement C1q Inhibitor ANX007 in Neurodegenerative Eye Disease

Ranibizumab Pharmacokinetics in Retinal Vein Occlusion