brolucizumab (DLX1008) / Athenex - LARVOL DELTA

EP. 4: Safety and Efficacy of Available Treatments in Wet AMD (Ophthalmology Times) - "Diana V. Do, MD: We were used to having such excellent safety profiles with the 3 most commonly used anti-VEGF agents: bevacizumab, ranibizumab, and aflibercept. More recently, the retina community faced some challenges with a new agent, brolucizumab, which was very efficacious. It had FDA approval, but later in the post marketing surveillance of this drug, we noticed some episodes of intraocular inflammation and severe adverse effects, such as retinal vascular occlusions...Charles C. Wykoff, MD, PhD: Great comment. Glad you brought that up. Let's dive into that. Mark, give us the mechanism of action. If you think about it historically, there's actually, right, there are 5 anti-VEGF agents that are FDA approved. We really use probably 3 of them, maybe a little of a fourth. We have aflibercept, bevacizumab, ranibizumab as Diana beautifully just said, and also pegaptanib as the first one on the block."

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DLX1008 (brolucizumab), a single-chain anti-VEGF-A antibody fragment with low picomolar affinity, leads to tumor involution in an in vivo model of Kaposi Sarcoma. (PubMed, PLoS One) - "We found that imaging by ultrasound was superior to external caliper measurements in the validation of the angiogenesis inhibitor DLX1008. Further development of DLX1008 against VEGF-dependent sarcomas is warranted."

Journal • Preclinical • Human Immunodeficiency Virus • Oncology • Sarcoma • Solid Tumor

Anti-tumor activity of DLX1008, an anti-VEGFA antibody fragment with low picomolar affinity, in human glioma models. (PubMed, J Pharmacol Exp Ther) - "Based on the response rate and improved progression-free survival, although not on overall survival, the 149-kDa anti-VEGF-A IgG antibody bevacizumab (Avastin) has been approved in the United States and Japan for recurrent glioblastoma and in Japan for newly diagnosed glioblastoma; however, it is not approved in the EU. In vivo, DLX1008 delayed growth in a mouse subcutaneous U87 xenograft model (p=0.0021) and improved survival in a mouse orthotopic U87 xenograft model (p=0.00026). Given its exceptionally high affinity and small molecule size, these data warrant further clinical development of DLX1008 as an antiangiogenic agent in glioblastoma."

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