"MRA" Phase III Trial Data to be Presented at The American College of Rheumatology Meeting

October 18, 2005 (Tokyo) - Chugai Pharmaceutical Co., Ltd. [Head Office: Chuo-ku, Tokyo; President Osamu Nagayama (hereinafter, "Chugai")] and F. Hoffmann-La Roche Ltd. (hereinafter "Roche") [Head Office: Basel, Switzerland. Chairman and CEO: Franz B. Humer] announced that the humanized anti-human IL-6 (interleukin-6) receptor monoclonal antibody, "MRA" (tocilizumab), globally co-developed by Chugai and Roche, has shown efficacy as a monotherapy in inhibiting the progression of joint destruction in phase III trial for rheumatoid arthritis patients conducted in Japan. The results will be presented at The American College of Rheumatology Annual Scientific Meeting held in San Diego, USA, from November 12 to 17.

The abstract of this publication is ready at the following ACR website:
http://www.abstractsonline.com/viewer/viewAbstract.asp?CKey={4521AFC3-F926-4C61-A7E5-2BF44D445EF5}&MKey={F5B9F43A-15A0-467D-8458-5DF32518B4E3}&AKey={AA45DD66-F113-4CDD-8E62-01A05F613C0D}&SKey={6DF59A4F-A41B-42DD-A069-6B5053D0757B}

Outline of the abstract:
- This phase III clinical trial is a randomized controlled trial conducted for 52 weeks in active rheumatic arthritis patients within five years of onset.
- 8 mg/kg tocilizumab (intravenous infusion) was administered every 4 weeks in the MRA arm (157 patients) while single or combination of conventional DMARDs, 80% of which was methotrexate (MTX), were administered in the control arm (145 patients). A total of 302 patients were evaluated.
- van der Heijde modified Sharp score was used to evaluate effects on joint destruction on the bone radiographs in blinded manner, and ACR response rates were used to determine the anti-rheumatic efficacy.
- Patients in the MRA arm showed statistically significant less radiographic joint destruction compared to the control group as measured by total Sharp score, erosion score and joint space narrowing. Also, ACR response rates in the MRA arm were statistically higher than those in the control arm.
- The over all incidences of adverse events including clinical laboratory abnormalities　were 96% and 87% in the MRA and control arms, respectively. Lipid increases were predominantly reported in the MRA arm, but the mean cholesterol level became stable at around the normal upper limit. No tuberculosis was observed.

MRA is currently marketed in Japan under the trade name "ACTEMRA^® 200 for Intravenous Infusion" after approval as a therapy for Castleman's disease in April this year. Outside of Japan, phase III trials in rheumatoid arthritis are going on in more than 20 countries worldwide through co-development between Chugai and Roche.

(Reference)

Total Sharp Score (TSS): Score to evaluate joint destruction of RA patients, which is calculated based on erosion score and joint space narrowing from bone radiographies.

Bone erosion: a region of the eroded surface of bone

Joint space narrowing: narrowing gap between components of a joint, according to progress of the disease

ACR response rate: The improvement criteria of American College of Rheumatology to evaluate disease activity of patients.  The response rate is a percentage of patients who are satisfied with the improvement criteria.

van der Heijde modified Sharp score: an evaluation method modified by Dr. van der Heijde, which contains evaluation of feet as well as hands and wrists (The original Sharp score is to evaluate only hands and wrists)