Drug giant AstraZeneca has signed a $1.3bn deal to develop and commercialise a drug to treat rheumatoid arthritis. AstraZeneca has licensed fostamatinib disodium (R788), an oral spleen tyrosine kinase (Syk) inhibitor, from Rigel Pharmaceuticals. Under the terms of the licensing agreement, Rigel will receive $100m upfront and an additional $345m in milestone payments. If the product is commercially successful, Rigel may receive a further $800m in salesrelated milestones, as well as doubledigit royalties on worldwide sales.
AstraZeneca is paying top dollar for R788, despite its failure in a Phase IIb trial last summer due to an unexpectedly high placebo response rate.
However, the market for diseasemodifying drugs for rheumatoid arthritis in the seven major markets was worth $7.4bn in 2008, according to market analysts Datamonitor. And biologics currently marketed to treat the disease are expensive and must be delivered by injection or intravenously.
‘There is an unmet need in the RA market for oral small molecule drugs that have equivalent efficacy to biologics, certainly if they are safe and less expensive in comparison,’ says analyst James Wentworth. ‘I believe AstraZeneca looked at the whole package of Phase II data and felt that, despite the shortcomings in the final Phase IIb trial, they could work around that with a large scale Phase III programme to help iron out any issues [side effects such as diarrhoea, hypertension and neutropenia].’
Another major driver behind AstraZeneca’s licensing of R788, says Wentworth, is that there is an immediate need to bring in late-stage pipeline projects following the halt of development of the company’s two Phase II drugs for rheumatoid arthritis last year.
Syk is involved in cell signalling of immune cells and is implicated in the pathogenesis of rheumatoid arthritis, other immunology indications and cancer. ‘The Phase I and early Phase II data certainly support proof of concept that targeting Syk would improve measured efficacy outcomes in RA,’ says Wentworth. And having completed Phase II trials, R788 is the furthest developed oral Syk inhibitor being evaluated for rheumatoid arthritis. Portola Pharmaceuticals has Syk-specific inhibitors for the disease in preclinical trials.
Meanwhile, Pfizer’s CP-690550, a small molecule JAK inhibitor with a different mechanism of action to R788, is currently undergoing a massive Phase III programme for rheumatoid arthritis and is likely to hit the market first, says Wentworth.
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