GSK takes aim at RA market, pitting otilimab against Pfizer and Sanofi rivals in phase 3

GlaxoSmithKline (GSK) has made a serious play for the lucrative rheumatoid arthritis (RA) drug market, announcing the beginning of a phase 3 development programme, involving a new class of antibody.

While the first wave of antibodies and biologics approved to treat rheumatoid arthritis were targeted against tumour necrosis factor (TNF), pharma has been trying to find other ways to tune down the overactive immune system that is the cause of RA.

GSK is hoping to outdo drugs from even these newer classes with a phase 3 programme based around otilimab, an investigational anti-granulocyte macrophage colony-stimulating factor (anti GM-CSF).

GSK noted the phase 3 clinical programme, named ‘ContRAst’, is the first in RA to include head-to-head comparisons of otilimab with current treatments across all pivotal studies.

The study will compare otilimab against two treatments with different modes of actions – Pfizer’s Janus Kinase (JAK) inhibitor Xeljanz (tofacitinib) and Sanofi/Regeneron’s interleukin-6 (IL-6) targeting

The UK pharma will test otilimab in patients who have had an inadequate response to disease modifying drugs or targeted therapies.

GSK’s chief scientific officer Dr Hal Barron has decided to move otilimab into late stage development following results of the phase 2 BAROQUE study announced in October last year.

The programme also enrols 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 compares the efficacy and safety of otilimab with placebo and with Xeljanz, 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 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 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.

Patients who complete the pivotal studies may be eligible to participate in a long-term extension study, contrast-X to further evaluate the efficacy and safety of otilimab for up to four years.

Hal Barron

Barron said: “Our phase 2 data showed encouraging clinical benefits in patients treated with otilimab. The unique phase 3 studies, designed in consultation with regulators, will help us understand how this potential new medicine could benefit appropriate patients living with rheumatoid arthritis.”