AstraZeneca announces top-line results from Phase III OSKIRA Trials of FOSTAMATINIB

AstraZeneca today announced top-line results from OSKIRA-2 and OSKIRA-3, the remaining pivotal Phase III clinical trials investigating fostamatinib, the first oral spleen tyrosine kinase (SYK) inhibitor in development as an oral treatment for rheumatoid arthritis (RA).

In the OSKIRA-2 study of patients inadequately responding to disease modifying anti-rheumatic drugs (DMARDs), fostamatinib in combination with DMARDs showed statistically significant improvements in ACR20 response rates at 24 weeks in both the 100mg twice daily group and the group receiving 100mg twice daily for four weeks followed by 150mg once daily (39.6%, p<0.001 both arms) compared to placebo (24.5%).

In the OSKIRA-3 study of patients inadequately responding to methotrexate (MTX) and a single TNF-alpha antagonist, fostamatinib in combination with MTX showed statistically significant improvements in ACR20 response rates at 24 weeks in the 100mg twice daily group (36.2%, p=0.004) but not in the group given 100mg twice daily for four weeks followed by 150mg once daily (27.8%, p=0.168) compared to placebo (21.1%).

The safety and tolerability findings for fostamatinib observed in the OSKIRA Phase III programme were generally consistent with those previously reported in earlier studies. The most commonly reported adverse events in the OSKIRA programme include hypertension, diarrhoea, nausea, headache and nasopharyngitis (common cold).

Based on the totality of results from the OSKIRA Phase III programme, including the data previously reported from OSKIRA-1, AstraZeneca has decided not to proceed with regulatory filings for fostamatinib. AstraZeneca will return the rights to the compound to Rigel Pharmaceuticals which will decide whether it will continue the ongoing studies and pursue regulatory filings.

Briggs Morrison, MD, Executive Vice President of Global Medicines Development and Chief Medical Officer, said: “The results of the late stage trials did not measure up to the promising results we saw earlier in development. We remain committed to the search for new treatments for patients with rheumatic and inflammatory diseases with Phase II compounds in rheumatoid arthritis and lupus and Phase III compounds in gout and psoriasis.”

As a result of this decision, AstraZeneca will incur a pre-tax impairment charge of approximately $140 million to R&D expense in the second quarter of 2013 for the intangible assets relating to fostamatinib. Since intangible asset impairments (except for IS-related intangibles) are excluded from the company’s Core financial measures, this impairment will have no impact on the company’s financial guidance for 2013, which is provided on a Core financial measures basis. As AstraZeneca will continue to incur some Core R&D costs associated with the completion of ongoing studies for fostamatinib, there is no change to the company’s guidance that it expects to hold Core operating costs for 2013 (combined Core SG&A and Core R&D) to a slight increase compared with 2012 on a constant currency basis.

AstraZeneca announced an exclusive worldwide license agreement with Rigel Pharmaceuticals in February 2010 for the global development and commercialisation of fostamatinib. AstraZeneca intends to publish a more detailed analysis of the OSKIRA clinical programme in due course.