GSK presents new efficacy and safety data of an anti GM-CSF antibody in patients with rheumatoid arthritis
22 October 2018
Issued: London UK
Marked patient benefit observed in phase II study supports further clinical development of GSK3196165 for RA.
GSK today announced encouraging results from a phase II dose-ranging study of 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). These data (abstract 1938) will be presented at the 2018 American College of Rheumatology (ACR).
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 (37 patients per arm) 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.
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.
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.”
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. The percentage of patients experiencing any AE or SAE respectively, was 49% and 0% for placebo, 51% and 5% for 22.5mg GSK165, 65% and 3% for 45mg GSK165, 59% and 5% for 90mg GSK165, 51% and 3% for 135mg GSK165, 65% and 0% for 180mg GSK165. There were no treatment limiting safety findings including serious infections, injection site reactions or laboratory abnormalities which were closely monitored throughout the study. No pulmonary toxicity, including pulmonary alveolar proteinosis, was observed.
In another 12-week study with 180mg GSK165 to be presented at the congress (abstract 2510), a similar clinical efficacy profile and in addition synovitis reduction was observed in patients with RA.
The results of the study (abstract 1938) will be presented on Monday 22 October 2018 (Session: Rheumatoid Arthritis – Treatments III: New Compounds and Biosimilars; 4:30 PM - 6:00 PM). Additional abstracts of GSK165 reporting results of the hand osteoarthritis study (abstract 1365), mechanistic RA study (abstract 2510) and exposure-efficacy analysis (2519) will be presented at the meeting and published in the abstract book.
GSK3196165 is not approved for use anywhere in the world.
Rheumatoid arthritis is a chronic, systemic inflammatory condition characterized by pain, joint swelling, stiffness, joint destruction and disability. It affects 24.5 million people globally1. Despite the use of disease modifying antirheumatic drugs, regarded the cornerstone of treatment, of which methotrexate is the gold standard, a substantial proportion of patients either fail to respond or have inadequate response. There is therefore a need for more effective treatments with alternative mechanism of action.
GSK3196165 is a human monoclonal antibody that inhibits granulocyte-macrophage colony-stimulating factor (GM-CSF), a type of protein that plays a central role in a broad range of immune mediated diseases, including rheumatoid arthritis. It activates cells, including macrophages (a white blood cell which plays a key role in the inflammatory process), leading to inflammation and joint damage. GSK3196165 neutralises the biological function of GM-CSF by blocking the interaction of GM-CSF with its cell surface receptor
In 2013 GSK assumed exclusive worldwide responsibility of GSK3196165 (previously MOR103) from MorphoSys AG for all development and commercialisation activities in all therapeutic fields.
The BAROQUE (Bringing Anti-GM-CSF to Rheumatoid Arthritis: A New Approach to Overcoming an InadeQUate ResponsE to MTX) study was a randomised, phase II, dose-ranging, multicentre, double-blind, parallel group, placebo-controlled study with the primary objective to assess the efficacy of GSK3196165, in combination with MTX, in patients with active moderate-severe RA despite prior treatment with MTX.
222 patients were randomised to receive placebo or subcutaneous GSK3196165 at doses of 22.5mg, 45mg, 90mg, 135mg or 180mg following a screening period of up to four weeks. The total treatment period was up to 52 weeks, with a 12-week follow-up period after the last dose (Week 50). At Week 12, patients receiving placebo or GSK3196165 doses between 22.5 – 135mg that failed to achieve a good/moderate EULAR response, could ‘escape’ to the 180mg dose of GSK3196165 to ensure that only patients with meaningful benefit could progress to long term treatment.
The primary endpoint used the disease activity score with CRP (DAS28(CRP)<2.6). Secondary endpoints included the DAS28(CRP) score, ACR response criteria (ACR20/50/70), EULAR response, global disease assessment, health assessment questionnaire disability index (HAQ-DI) score, simple disease activity index (SDAI), clinical disease activity index (CDAI) and functional assessment of chronic illness therapy (FACIT)-fatigue score.
GSK – one of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For further information please visit www.gsk.com.
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Cautionary statement regarding forward-looking statements
GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D 'Principal risks and uncertainties' in the company's Annual Report on Form 20-F for 2017.