Anglo-Swedish drug giant AstraZeneca has kicked off a Phase III clinical trial of its newly-acquired oral syk inhibitor fostamatinib, to assess its potential as a novel treatment for rheumatoid arthritis.
The drugmaker said it has now enrolled the first patient in the study, which is looking at the use of fostamatinib - bought from Rigel Pharmaceuticals in a deal worth up to $1.25 billion in February - to treat patients who have had an inadequate response to disease modifying anti-rheumatic drugs (DMARDs) such as methotrexate (MTX).
Under the clinical programme, crowned OSKIRA (Oral Syk Inhibition in Rheumatoid Arthritis), three pivotal Phase III trials will test the drug’s efficacy and tolerability, two 12-month studies will examine the effect of fostamatinib on patients not responding to DMARDs, and a six-month trial will assess the drug’s effect on patients who failed to respond to prior anti-TNF therapy. Safety will also be looked at in extension studies.
Two doses of fostamatinib will be studied in programme; a 100mg twice-daily regimen and a second regimen investigating 100mg twice daily for four weeks followed by a maintenance dose of 150mg once daily. And primary outcome measures across the three studies include the standard benchmark ACR 20 response rate at six months, as well as change in structural progression in one of the 12-month trials, the drugmaker said.
Fostamatinib, previously referred to as R788, has the potential to become the first in a new class of treatments for RA, being the most advanced oral spleen tyrosine kinase (Syk) inhibitor in development, and is thought to block intracellular signalling between various immune cells playing a role in the destruction of bone and cartilage as seen in the disease.
While two previous Phase II trials comparing the drug to MTX demonstrated fostamatinib’s promise, its clinical progress was marred by results of a smaller study with 219 patients who had failed biologic therapies, which, although showing some signs of efficacy, missed its primary endpoint.
Still, AstraZeneca is clearly confident in the drug’s potential. “Patients with rheumatoid arthritis currently have limited treatment options after they stop responding adequately to DMARDs or anti-TNF therapy, and we are hopeful that fostamatinib may represent a novel alternative for patients to help manage their condition beyond this stage,” noted Anders Ekblom, AstraZeneca’s executive vice president of Global Medicines Development.
The company said it expects to submit the first regulatory filings based on the OSKIRA programme sometime in 2013.