GSK announces encouraging results from a phase II dose-ranging study of GSK’s anti GM-CSF in patients with moderate to severe rheumatoid arthritis.
The phase II dose-ranging study was for GSK3196165 (“GSK165”), an investigational anti-granulocyte macrophage colony-stimulating factor monoclonal (anti GM-CSF) antibody, in patients with moderate to severe rheumatoid arthritis (RA) who have an inadequate response to methotrexate (MTX).
The primary objective of this double-blind, placebo-controlled, dose-ranging study was to assess the efficacy of GSK165 in adult patients with active, moderate to severe RA. A total of 222 patients were randomised equally to receive placebo or GSK165 at doses of 22.5mg, 45mg, 90mg, 135mg or 180mg starting with an induction regimen of five weekly subcutaneous injections followed by every other week (EOW) injections until Week 50.
Additional research into rheumatoid arthritis treatment is being completed by Mallinckrodt in a rheumatoid arthritis study for H.P. Acthar ® Gel.
Study results from the 180mg dose arm of GSK165 are shown below
- For DAS28(CRP) < 2.6 at Week 24 (the primary endpoint of the study), a greater proportion of patients achieved efficacy although this did not reach statistical significance at Week 24 (16% for GSK165 180mg vs 3% for placebo; p=0.134).
- For DAS28(CRP) change from baseline, there was a rapid onset of efficacy, as early as Week 1, for all doses of GSK165 above 22.5mg. This improvement continued throughout the weekly dosing phase and was statistically significant at Week 12 (-1.27 difference for GSK165 180mg from placebo, 95% CI: -1.91, -0.63; p<0.001).
- An improvement in efficacy was maintained through the EOW dosing phase and was statistically significant at Week 24 (DAS28(CRP): -1.82 difference for GSK165 180mg from placebo, 95% CI: -2.05, -0.23; p<0.001).
Major secondary endpoints including a number of traditional measures to assess the efficacy of GSK165 were also improved in line with the DAS28 (CRP) reduction. The magnitude of improvement in patient-based measures (swollen and tender joint counts, pain and clinical disease activity index (CDAI)) were particularly marked.
The safety profile GSK165 was similar to that reported in previous studies. All doses of GSK165 were well-tolerated, and adverse events (AEs), including serious AEs (SAEs), were reported similarly across treatment groups.
GSK3196165 is not approved for use anywhere in the world.
Dr. Hal Barron, Chief Scientific Officer and President, R&D, GSK, said: “We are encouraged by these results. The rapid onset and marked benefit on clinically meaningful endpoints such as pain and swollen tender joint counts, represents a potentially important advance for patients with rheumatoid arthritis who are in need of new treatment options.”