Could Kyowa Kirin be eyeing ophthalmology use for cancer drug tivozanib?

Kyowa Kirin has bought back rights outside of cancer to tivozanib, amending an agreement dating back to 2006 with AVEO, and opening up the possibility of research in ophthalmology.

Under the terms of the deal Kyowa Kirin will buy back the non-cancer rights of tivozanib in territories included in the deal, which covers the US and EU.

This also excludes rights sublicensed to EUSA Pharma, which markets the drug under the brand name Fotivda in Europe for kidney cancer.

This amends the deal in 2006 which granted AVEO exclusive rights to tivozanib in all indications.

Kyowa Kirin will make an upfront payment of $25 million to AVEO and waive the latter’s obligation to make an $18 million milestone payment upon marketing approval, and up to $391 million in payments upon achievement of certain development and commercial objectives in non-oncology uses.

The Japanese pharma is not saying how it intends to develop tivozanib, but tivozanib is a vascular endothelial growth factor (VEGF) inhibitor, which works by inhibiting the growth of blood vessels that feed tumours.

VEGF inhibitors are also used in ophthalmology – Novartis’ Lucentis (ranibizumab) is an antibody that inhibits VEGF that has already been approved in ophthalmology indications such as wet age-related macular degeneration (AMD).

In this disease, blood vessels proliferate in the back of the eye, scarring it and leading to loss of central vision.

VEGF inhibitors work against these blood vessels, improving the vision of people affected by AMD and similar diseases.

Roche’s Avastin (bevacizumab), another VEGF drug used in cancer, is not approved in ophthalmology but is used off-label in diseases such as wet AMD as it is cheaper to administer than Lucentis.

Kyowa Kirin gave no further details about what the “non-oncology” uses agreement covers but ophthalmology has proven to be a highly lucrative market for Novartis and its rival Bayer, which markets another VEGF drug, Eylea (aflibercept).

Tivozanib has already been studied in mice with choroidal neovascularisation, with results suggesting a possible use in neovascular AMD.

And as the VEGF inhibitors on the market are expensive biologic drugs, repurposing a small molecule drug such as tivozanib could give Kyowa Kirin wiggle-room in terms of pricing should clinical trials go well.