GSK announces phase III start for its anti GM-CSF antibody, otilimab, in patients with rheumatoid arthritis (RA)

Issued: London, UK

GSK today announced the start of a phase III clinical development program with otilimab, an investigational anti-granulocyte macrophage colony-stimulating factor (anti GM-CSF) monoclonal antibody, for patients with moderate to severe rheumatoid arthritis (RA) who have had an inadequate response to disease modifying antirheumatic drugs (DMARD) or targeted therapies.

The progression of otilimab (previously GSK3196165) into phase III follows the results of the phase II BAROQUE study which were announced in October 2018.

Dr Hal Barron, Chief Scientific Officer and President, R&D, GSK, said: “Our phase II data showed encouraging clinical benefits in patients treated with otilimab. The unique phase III studies, designed in consultation with regulators, will help us understand how this potential new medicine could benefit appropriate patients living with rheumatoid arthritis.”

The phase III clinical program (named ‘ContRAst’) is the first in RA to include head-to-head comparisons of otilimab with current treatments across all pivotal studies.  It compares otilimab against two treatments with different modes of actions: tofacitinib (a Janus Kinase (JAK) inhibitor) and sarilumab (an anti-IL6). The program also enrolls a broad range of difficult-to-treat patients who have had an inadequate response to or have been unable to tolerate currently available treatments.  It comprises three pivotal studies and a long-term extension study. The primary endpoint for the pivotal studies is the proportion of patients achieving the American College of Rheumatology criteria (ACR20) at week 12 (against placebo).

• contRAst-1 (201790): Compares the efficacy and safety of otilimab with placebo and with tofacitinib, all in combination with methotrexate (MTX), over 52-weeks in approximately 1500 -1700 patients with moderately to severely active RA who have an inadequate response to MTX.

• contRAst-2 (201791): Compares the efficacy and safety of otilimab with placebo and with tofacitinib, all in combination with conventional synthetic DMARDs, over 52-weeks in approximately 1500-1800 patients with moderately to severely active RA who have an inadequate response to conventional synthetic DMARDs or biologic DMARDs.

• contRAst-3 (202018): Compares the efficacy and safety of otilimab with placebo and with sarilumab, all in combination with conventional synthetic DMARDs, over 24-weeks in approximately 500-600 patients with moderately to severely active RA who have an inadequate response to biological DMARDs and/or JAK inhibitors.

• contRAst-X (209564): Patients who complete the pivotal studies may be eligible to participate in a long-term extension study to further evaluate the efficacy and safety of otilimab for up to 4 years.

Otilimab is not approved for use anywhere in the world.

About the Phase III contRAst Studies

The phase III contRAst studies will compare the efficacy and safety of two doses of otilimab (90mg and 150mg subcutaneous weekly injection) with placebo, tofacitinib 5mg capsules twice daily and sarilumab 200mg subcutaneous injection every other week, all in combination with MTX or conventional synthetic DMARDs. The primary endpoint for the pivotal studies is the proportion of patients achieving the American College of Rheumatology criteria (ACR20) at week 12 (against placebo). Major secondary endpoints across the studies include the clinical disease activity index (CDAI) score or response criteria, health assessment questionnaire disability index (HAQ-DI) score and pain against placebo, tofacitinib and/or sarilumab. The clinical programme will be conducted across 32 countries globally.

About the Phase II BAROQUE Study

The phase II BAROQUE (Bringing Anti-GM-CSF to Rheumatoid Arthritis: A New Approach to Overcoming an InadeQUate ResponsE to MTX) dose-ranging study compared the efficacy of otilimab (22.5mg, 45mg, 90mg, 135mg or 180mg) with placebo, in combination with MTX, in 222 patients with active moderate-severe RA despite prior treatment with MTX.

The primary endpoint was the disease activity score with CRP (DAS28(CRP)<2.6) at Week 24. Secondary endpoints included the DAS28(CRP) score, ACR response criteria (ACR20/50/70), EULAR response, global disease assessment, HAQ-DI score, simple disease activity index (SDAI), CDAI and functional assessment of chronic illness therapy (FACIT)-fatigue score.

The results were announced and presented at an investor call and at the American College of Rheumatology (abstract 1938) in October 2018.

About RA

Rheumatoid arthritis is a chronic, systemic inflammatory condition characterized by pain, joint swelling, stiffness, joint destruction and disability. It affects 24.5 million people globally. 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 an inadequate response. There is therefore a need for more effective treatments with alternative mechanism of action.

About Otilimab

Otilimab (previously GSK3196165) is a fully human monoclonal antibody that inhibits granulocyte-macrophage colony-stimulating factor (GM-CSF), a protein that plays a central role in a broad range of immune-mediated diseases, including rheumatoid arthritis. GM-CSF acts on cells, including macrophages (an immune cell type that plays a key role in the inflammatory process), leading to inflammation, joint damage and pain. Otilimab 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 otilimab from MorphoSys AG for all development and commercialization activities in all therapeutic fields.

About GSK

GSK is a science-led global healthcare company with a special purpose: to help people do more, feel better, live longer. For further information please visit about us.

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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 2018.

References

1. GBD 2015 Disease and Injury Incidence and Prevalence, Collaborators. "Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet (2016). 388 (10053): 1545–1602.