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Long-acting protein drugs for the treatment of ocular diseases

Ghosh, Joy and Nguyen, Andrew and Bigelow, Chad and Poor, Stephen and Qiu, Yubin and Rangaswamy, Nalini and Ornberg, Richard and Jackson, Brittany and Mak, Howard and Ezell, Tucker and Ashminova, Vania and De La Cruz, Elisa and Carrion, Ana and Etemad-Gilbertson, Bijan and Garcia Caro, Roxana and Zhu, Kan and George, Vinney and Bai, Jirong and Sharma, Radhika and Shen, Siyuan and Wang, Yiqin and Subramanian, Kulandayan and Fassbender, Elizabeth and Maker, Michael and Hanks, Shawn and Vrouvlianis, Joanna and Leehy, Barrett and Long, Debby and Prentiss, Melissa and Kansara, Viralbhai and Jaffee, Bruce and Dryja, Ted and Roguska, Michael (2017) Long-acting protein drugs for the treatment of ocular diseases. Nature communications, 8. pp. 1-10. ISSN 2041-1723

Abstract

Protein drugs that neutralize vascular endothelial growth factor (VEGF), such as aflibercept or
ranibizumab, rescue vision in patients with retinal vascular diseases. Nonetheless, optimal
visual outcomes require intraocular injections as frequently as every month. Here we report
a method to extend the intravitreal half-life of protein drugs as an alternative to either
encapsulation or chemical modifications with polymers. We combine a 97-amino-acid
peptide of human origin that binds hyaluronan, a major macromolecular component of the
eye’s vitreous, with therapeutic antibodies and proteins. When administered to rabbit and
monkey eyes, the half-life of the modified proteins is increased B3–4-fold relative to
unmodified proteins. We further show that prototype long-acting anti-VEGF drugs (LAVAs)
that include this peptide attenuate VEGF-induced retinal changes in animal models of
neovascular retinal disease B3–4-fold longer than unmodified drugs. This approach has the
potential to reduce the dosing frequency associated with retinal disease treatments.

Item Type: Article
Date Deposited: 28 Mar 2017 00:45
Last Modified: 28 Mar 2017 00:45
URI: https://oak.novartis.com/id/eprint/31351

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