AstraZeneca’s (AZ) efforts to replenish its product portfolio were hit yesterday after the company said it would drop rheumatoid arthritis (RA) candidate fostamatinib from development after negative phase III results.
The pharma company took the decision not to proceed with regulatory filings for fostamatinib after reporting mixed top-line results from the OSKIRA-2 and OSKIRA-3 studies, which looked at the drug’s use as a second-line therapy in RA.
Fostamatinib was licensed to AZ by US biotechnology firm Rigel in 2010 and is a first-in-class spleen tyrosine kinase (SYK) inhibitor, pitched as a possible oral alternative to injectable RA drugs such as AbbVie’s Humira (adalimumab).
In OSKIRA-2, fostamatinib was added to disease-modifying anti-rheumatic drugs (DMARDs), such as methotrexate (MTX), in patients who had an inadequate response to DMARDs given alone, while in OSKIRA-3 it was given to those who had failed therapy with MTX and a TNF antagonist such as Humira.
While the drug showed some efficacy in the trials, the results were not compelling enough for AZ to continue to invest in its development. It has therefore opted to return rights to Rigel.
There had already been signs that the fostamatinib project was not firing on all cylinders. Last December, for example, the OSKIRA-4 trial showed that fostamatinib was unable to match the efficacy of Humira in patients who were ineligible for treatment with DMARDs, or had never been treated with this type of drug. Then, in April, fostamatinib missed one of two primary outcome measures in the OSKIRA-1 trial.
Analyst Savvas Neophytou of Panmure Gordon said the news “reminds investors that [AZ] carries significant pipeline execution risk” as the company’s exclusivity on cholesterol blockbuster Crestor (rosuvastatin) comes to an end in many territories.
Fostamatinib was looking increasingly like a minor product – with sales consensus of $150m in 2016 following the release of the OSKIRA-4 results – and AZ appears to have done the right thing in handing it back as the latest data suggests it has more side effect issues than Pfizer’s Xeljanz (tofacitinib), another rival RA therapy cleared by the US FDA in 2012.
The latest studies suggest fostamatinib is linked to increases in blood pressure and diarrhoea, said Neophytou.