Roche has submitted a filing to the European health authorities (the European Medicines Agency) to extend the indication of RoACTEMRA to inhibit the progression of joint damage and to improve physical function in patients with rheumatoid arthritis (RA). Joint damage in RA often begins early in the disease and can lead to permanent disability, so inhibiting this structural damage to patients' joints is a critical measure of effectiveness of an RA treatment.
"A successful regulatory outcome will be an important milestone for RoACTEMRA. It will give both physicians and patients further confidence that RoACTEMRA not only helps achieve a long-lasting remission from the painful and debilitating disease symptoms, but that it inhibits the progression of structural joint damage which is the major cause of loss of normal function and permanent disability for RA patients," said Urs Schleuniger, Roche's Global Product Strategy head, Inflammation/Immunology.
The filing follows positive two-year data from the LITHE1 pivotal trial. Results from the trial showed that patients receiving RoACTEMRA in combination with methotrexate (MTX) had significantly less damage to their joints at two years, compared to patients who received MTX alone. The outcome was determined by x-ray evidence of the progression of bone erosions and narrowing of joint spaces.
RoACTEMRA is currently licensed in Europe for use in combination with MTX, to treat adult patients with moderate to severe RA who responded inadequately to, or who were intolerant to, previous therapy with one or more disease modifying anti-rheumatic drugs (DMARDs) or tumour necrosis factor antagonists (anti-TNFs). In these patients, RoACTEMRA can be given as a monotherapy in cases of intolerance to MTX or where continued treatment with MTX is inappropriate.
The LITHE study, a randomized, double-blind, placebo-controlled trial was designed to evaluate the efficacy of TCZ plus MTX in preventing structural joint damage and improving physical function over two years. LITHE is an international study, including 15 countries and 1196 patients with moderate to severe RA who had an inadequate response to MTX. In this randomized study, patients received either RoACTEMRA (4 mg/kg or 8 mg/kg, one infusion every four weeks) in combination with MTX or MTX alone.
Results from the 12-month analysis showed that at 52 weeks, total Genant-modified Sharp Score changes from baseline for the RoACTEMRA 8mg + MTX, 4mg +MTX, and MTX alone groups were: 0.29, 0.34 and 1.1 respectively. The percentage of patients achieving no progression in total Genant-modified Sharp Score was 85 per cent, 81 per cent and 67 per cent. Results from two global measures, the HAQ-DI4 for physical function, and the DAS285 for clinical remission, both demonstrated a benefit in the treatment groups. The HAQ-DI AUC change from baseline, adjusted mean scores were: -144.1, -128.4 and -58.1 respectively. DAS28 clinical remission (<2.6) was 47 per cent, 30 and 8 per cent.
The recently announced two-year data from the LITHE study demonstrate that ACTEMRA continues to be highly effective at inhibiting joint structural damage and maintaining consistently high remission rates as seen in the one-year results. The study outcomes will be presented at the Annual Meeting of the American Society of Rheumatology (ACR) in October.
RoACTEMRA is the result of research collaboration by Chugai and is being co-developed globally with Chugai.