Fostamatinib at the EULAR 2012

New data from the EULAR 2013 at: http://rheumatologe.blogspot.de/2013/06/fostamatinib-at-eular-2013.html



Concerning fostamatinib (a SYK inhibitor, SYK stand for spleen tyrosine kinase), how far have we come during the past year?

I have already referred to the study of E. Salgado and colleagues, who systematically reviewed the safety of protein kinase inhibitors in clinical trials in rheumatoid arthritis. They found dizziness in 5%, rash in 6%, increased AST/ALT in 15% (!), hypertension in 13% (!),diarrhea in 17% (!),headaches in 8%, and neutropenia in 7% of patients treted with fostamatinib. So adverse events are an issue with this SYK inhibitor. No wonder that the studies presented at the EULAR 2012 meeting are looking at safety issues.

P. Martin and colleagues studied effects on R406 (the active metabolite of fostamatinib) pharmacokinetics in a total of 32 volunteers with hepatic impairment in Child-Pugh Classes A-C and volunteers with normal hepatic function (each group had eight individuals). As hepatic impairment didn´t affect the exposure of the active metabolite R406 to an extent that would be considered clinically relevant, they concluded that there is no need for dose reduction of fostamatinib in patients with impaired hepatic function.

[THU0139] PHARMACOKINETICS OF FOSTAMATINIB IN PATIENTS WITH IMPAIRED HEPATIC FUNCTION: A PHASE I STUDY
P. Martin1, S. Oliver1, M. Gillen1, T. Marbury2, D. Millson1. 1AstraZeneca Pharmaceuticals, Macclesfield, United Kingdom; 2Orlando Clinical Research Center, Orlando, United States
Conclusions: Hepatic impairment did not affect the exposure of the active metabolite R406 to an extent that would be considered clinically relevant. Consequently, there is no expectation of a need for fostamatinib dose reduction in hepatically impaired subjects.

The same group looked at 24 subjects with normal, moderately and severly impaired renal function. As rrenal impairment didn´t affect the exposure of the active metabolite R406 to an extent that would be considered clinically relevant, they concluded that there is no need for dose reduction of fostamatinib in patients with impaired renal function.

[THU0138] PHARMACOKINETICS OF FOSTAMATINIB IN PATIENTS WITH IMPAIRED RENAL FUNCTION: A PHASE I STUDY
P. Martin1, S. Oliver1, M. Gillen1, T. Marbury2, D. Millson1. 1AstraZeneca Pharmaceuticals, Macclesfield, United Kingdom; 2Orlando Clinical Research Center, Orlando, United States
Conclusions: Renal impairment did not affect the exposure of the active metabolite R406 to an extent that would be considered clinically relevant. Consequently, there is no expectation of a need for fostamatinib dose reduction in renally impaired subjects.

It looks a bit too good not to cause suspicion, not in the results but in the relevance. I think we should look careful at the results of the studies that are to come in the next two years. Larger numbers of patients in phase 2 studies would make me more confident that fostmatinib may become a useful drug in the treatment of rheumatoid arthritis.