Investor Update

Basel, 16 June 2010

New RoACTEMRA data reinforces its role as an innovative treatment for patients living with Rheumatoid Arthritis

Data to be presented at EULAR shows early improvement in inflammation and pre-existing joint damage

New data presented this week at the European League Against Rheumatism (EULAR) congress show that in some patients improvement in inflammation of the joint-lining membrane (synovitis) was achieved as early as week two when treated with RoACTEMRA  (known as ACTEMRA outside Europe). Furthermore, 12% of patients treated with RoACTEMRA saw improvements in pre-existing joint damage (bone erosions).  

In addition, RoACTEMRA reduced synovitis in 32 percent of patients after 12 weeks and 28 percent of patients showed improvement in osteitis (a pre-stage of bone erosion) within 12 weeks of treatment initiation. Joint damage occurs most rapidly within the first six months of disease and can lead to permanent disability. Therefore stopping the progression of this damage is a critical measure of the effectiveness of an RA treatment.

Commenting on the significance of these findings, Professor Philip Conaghan, Professor of Musculoskeletal Medicine, University of Leeds, UK said, “Not only does RoACTEMRA have established efficacy in treating RA including the inhibition of progressive joint destruction, but these  data demonstrate that RoACTEMRA may have the potential to heal existing bone erosions. This is exciting news for patients who fear long-term disability associated with the progressive effects of this condition.”

These findings add to the data submitted to the European Medicines Agency for the recent approval of RoACTEMRA to reduce the rate of progression of joint damage and improve physical function in patients with RA, when given in combination with methotrexate.

This data from an interim analysis of a substudy of the Phase IIIb ACT-RAY study was obtained through low-field extremity MRI, a special form of MRI scanning that is suitable for use in a physician’s office setting. The changes in erosion, osteitis and synovitis were measured using the RAMRIS* scoring system.

In addition to the ACT-RAY study, data from the Rapid Onset and Efficacy (ROSE) study further demonstrates RoACTEMRA’s rapid and sustained efficacy, with significantly reduced disease activity (reduction of DAS28) in some patients as early as one week after treatment.   Further Phase IIIb studies , , TAMARA and ACT-SURE, support RoACTEMRA’s efficacy and safety profile in a real-life setting. Findings from these studies show that almost half of patients achieved DAS28 remission after six months’ treatment with the safety profile being consistent with that of the pivotal Phase III developmental programme. Long term data from the extensions of the RoACTEMRA phase III programme reinforced these findings showing that the rates of adverse events and serious adverse events were stable over a median duration of 2.6 years.

* Rheumatoid Arthritis Magnetic Resonance Imaging Scoring system

About the Studies

ACT-RAY

The Phase IIIb ACT-RAY MRI Substudy examined the early effects of RoACTEMRA on synovitis and osteitis in patients with erosive RA who were inadequate responders to methotrexate (MTX). It involved 63 patients on stable MTX dose, randomised to continue stable MTX dose or receive placebo; both arms also received RoACTEMRA (8mg/kg IV) every 4 weeks. MR images were scored using the RAMRIS method and blinded data from both RoACTEMRA arms were pooled and analysed. Results showed at week 2, 44% patients had improved synovitis scores and 7% patients had improved scores ≥ smallest detectable change (SDC). At week 12, 65% patients had improved synovitis scores and 32% patients had improved ≥ SDC. By week 12, median osteitis score improved from baseline and 28% patients had improved ≥ SDC. Median erosion score did not change, but 10 patients showed erosion score change ≥ SDC at week 12.

TAMARA

The German, multi-center, open-label, non-controlled Phase IIIb study, supports the effectiveness and safety of RoACTEMRA in a setting close to real-life medical care. 239 adults with moderate to severe RA despite treatment with conventional and/or biologic DMARDs were treated with RoACTEMRA for 24 weeks. At week 24, 57% patients had achieved the primary endpoint of DAS28 “low disease” (LDAS ≤3.2). A “good” or “moderate” EULAR response was achieved by 75.2% patients in total. A clinically significant DAS28 reduction from Baseline (≥1.2) was documented in 74.5% of patients and 47.6% achieved a DAS remission (<2.6). ACR20/50/70 response rates at week 24 were 65.0%/50.7%/33.9%.

ACT-SURE

The Phase IIIb ACT-SURE study examined 1669 DMARD IR or anti-TNF IR patients treated with either RoACTEMRA alone or in combination with DMARDs over 6 months. Patients with active RA received RoACTEMRA 8mg/kg every 4 weeks. Patients were grouped by prior anti-TNF use for analysis: naïve, prior use (>2 months since washout) and recent use (≤2 months of baseline). Results showed that safety did not differ substantially among groups, and ACR and DAS28 responses were comparable or higher than in most earlier studies.

ROSE

The Rapid Onset and Systemic Efficacy (ROSE) study assessed the efficacy of RoACTEMRA versus placebo in combination with DMARDs in reducing the signs and symptoms during 24 weeks of treatment in patients with moderate to severe RA who have had inadequate clinical response to DMARDs. 619 patients were involved in the study. At week 24, RoACTEMRA showed a significantly higher percentage of ACR50 (primary end point) responders compared with control (30.1% vs 11.2%). Statistically significant differences between treatment groups were demonstrated for ACR20, ACR50 and ACR70 response rates through to week 24. Similar results were obtained for DAS28 and RAPID3 scores. In a subset of 62 patients, more patients achieved DAS28 remission (DAS28 <2.6) with RoACTEMRA than control and DAS28 responses were significantly improved only 1 week after treatment.

Long-Term Safety

This analysis assessed the long-term safety of RoACTEMRA in 4009 patients with RA over a median of 2.6 years, using pooled data from ongoing long-term extension studies. Patients included in the analysis received ≥1 dose of RoACTEMRA in the 24-week Phase III clinical trials (OPTION, AMBITION, RADIATE, TOWARD), in the 2-year Phase III clinical trial (LITHE), in a Phase I study, or in the ongoing, open-label extension studies (GROWTH95, GROWTH96). Results demonstrated that no new safety signals have emerged with prolonged exposure to RoACTEMRA. During longer-term treatment with RoACTEMRA, the rates of adverse events and serious adverse events were stable over time. These data further support a favourable benefit/risk profile for RoACTEMRA use in patients with moderate to severe RA.

About RoACTEMRA/ACTEMRA

RoACTEMRA/ACTEMRA is the result of research collaboration by Chugai and is also being co-developed globally with Chugai. RoACTEMRA/ACTEMRA is the first humanised interleukin-6 (IL-6) receptor-inhibiting monoclonal antibody. An extensive clinical development programme of five Phase III trials was designed to evaluate clinical findings of RoACTEMRA/ACTEMRA, all of which met their primary endpoints. RoACTEMRA/ACTEMRA was first approved in Japan, and launched by Chugai in June 2005 as a therapy for Castleman's disease; in April 2008, additional indications for rheumatoid arthritis (RA), polyarticular juvenile idiopathic arthritis and systemic-onset juvenile idiopathic arthritis were also approved in Japan. RoACTEMRA/ACTEMRA was approved in the European Union in January 2009 for the treatment of RA in patients who have either responded inadequately to, or who were intolerant to, previous therapy with one or more disease modifying anti-rheumatic drugs (DMARDs) or tumour necrosis factor (TNF) inhibitors. It is also approved for use in several other countries, including India, Brazil, Switzerland, and Australia. RoACTEMRA/ACTEMRA was most recently (January 2010) approved in the United States for the treatment of adult patients with moderately to severely active RA who have had an inadequate response to one or more TNF inhibitors.

The overall safety profile of RoACTEMRA/ACTEMRA is consistent across all global clinical studies. The serious adverse events reported in RoACTEMRA/ACTEMRA clinical studies include serious infections, gastrointestinal perforations and hypersensitivity reactions including anaphylaxis. The most common adverse events reported in clinical studies were upper respiratory tract infection, nasopharyngitis, headache, hypertension and increased ALT.  Increases in liver enzymes (ALT and AST) were seen in some patients; these increases were generally mild and reversible, with no evidence of hepatic injuries or any observed impact on liver function.  Laboratory changes, including increases in lipids (total cholesterol, LDL, HDL, triglycerides) and decreases in neutrophils and platelets, were seen in some patients without association with clinical outcomes. Treatments that suppress the immune system, such as ACTEMRA, may cause an increase in the risk of malignancies.

About Roche

Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world’s largest biotech company with truly differentiated medicines in oncology, virology, inflammation, metabolism and CNS. Roche is also the world leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management. Roche’s personalised healthcare strategy aims at providing medicines and diagnostic tools that enable tangible improvements in the health, quality of life and survival of patients. In 2009, Roche had over 80’000 employees worldwide and invested almost 10 billion Swiss francs in R&D. The Group posted sales of 49.1 billion Swiss francs. Genentech, United States, is a wholly owned member of the Roche Group. Roche has a majority stake in Chugai Pharmaceutical, Japan. For more information: www.roche.com.

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