AstraZeneca (AZ) suffered another pipeline setback after its rheumatoid arthritis (RA) candidate fostamatinib failed to meet expectations in a phase IIb trial.
The results of the six-month OSKIRA-4 study showed that fostamatinib was more effective than placebo in RA when used as a monotherapy, but could not match the efficacy of Abbott Laboratories’ Humira (adalimumab), the comparator drug in the trial.
OSKIRA-4 involved patients who were ineligible for treatment with disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate, or had never been treated with this type of drug.
If replicated in phase III trials the finding would hold back commercial prospects for fostamatinib, which has been regarded as one of the most important candidates in AZ’s clinical pipeline.
The drug, licensed to AZ by US biotechnology firm Rigel in 2010, is a first-in-class spleen tyrosine kinase (SYK) inhibitor, and could be an oral alternative to biologic RA drugs such as Humira which are delivered by injection.
It is thought to work by blocking signalling in multiple cell types involved in inflammation and tissue degradation, and is AZ’s “most likely blockbuster emerging from its pipeline”, according to analysts at Panmure Gordon.
They raised concerns that Humira was significantly better than fostamatinib in such as small and statistically low-powered study, particularly as AZ’s drug was less effective than Humira on all of the doses tested, which were 100mg twice-daily, 100mg twice-daily for a month followed by 150mg once-daily, and 100mg twice-daily for a month followed by 100mg once-daily.
AZ is focusing on the use of the fostamatinib as part of a combination therapy for RA alongside other DMARDs, but the failure to match Humira as a monotherapy is a disappointment and “likely to limit the product’s commercial potential”, according to the analysts who are predicting $275m in 2017 sales, assuming a launch in 2014.
The company’s phase III programme for fostamatinib consists of three studies and will provide “a more comprehensive assessment of the benefit/risk profile of fostamatinib used in combination with a DMARD”, commented AZ’s R&D chief Martin Mackay.
The pivotal trials are due to report results in the first half of 2013, and if positive filings in the EU and US will follow later in the year.