Ocrelizumab could cause deaths in rheumatoid arthritis patients; Roche, Biogen-Idec suspends clinical trials

Clinical studies of ocrelizumab, an investigational therapy for rheumatoid arthritis by Roche Holding AG and Biogen Idec have been suspended after it caused deaths in some patients in trials.

Ocrelizumab is a humanized monoclonal antibody that selectively binds to a particular protein – the CD20 antigen – on the surface of B-cells, which are believed to play a critical role in immunologic diseases.

Ocrelizumab binds to and eliminates CD20-positive B-cells. Stem cells (B-cell progenitors) in bone marrow lack the CD20 antigen, allowing healthy B-cells to regenerate after treatment and eventually return to normal levels.

Ocrelizumab is also being studied in patients with multiple sclerosis.

In December 2009, Roche announced Phase III study (STAGE) of ocrelizumab given in combination with methotrexate (MTX) met its primary endpoint of improving signs and symptoms (as measured by American College of Rheumatology or ACR20 response) in rheumatoid arthritis (RA) patients who had an inadequate response to MTX at both 24 and 48 weeks.

The FILM study in MTX-naïve RA patients was placed on clinical hold following an assessment of benefit to risk in this specific  rheumatoid arthritis patient population.

The BELONG study in lupus nephritis patients was previously halted due to serious and opportunistic infection signals.

Roche and Biogen Idec announced their decision to suspend ocrelizumab treatment of patients in the rheumatoid arthritis (RA) programme following the recommendation of the independent ocrelizumab RA & Lupus Data and Safety Monitoring Board (DSMB) based on their assessment of the studies in rheumatoid arthritis (SCRIPT, FEATURE, FILM and STAGE) and lupus (BELONG and BEGIN).

The DSMB concluded that the safety risk outweighs the benefits observed in these specific patient populations at this time.

The DSMB review detected an infection related safety signal which included serious and opportunistic infections, some of which were fatal.

“Patient safety is of the utmost importance in all of our drug development programmes. In light of the DSMB recommendations we have decided to suspend Ocrelizumab treatment in the RA clinical development programme .” said Hal Barron, MD executive vice president and Chief Medical Officer at Roche.

The SCRIPT trial in patients who inadequately responded to one or more TNF antagonists and the FILM trial remain blinded. A detailed analysis of all of the data will be conducted to help further inform the future of the Ocrelizumab RA clinical programme.

Ocrelizumab is also being evaluated for relapsing remitting multiple sclerosis (RRMS). The treatment in the ocrelizumab RRMS Phase II study is on-going at this time.

Headquartered in Basel, Switzerland, Roche is the world’s largest biotech company with  medicines in oncology, virology, inflammation, metabolism and CNS.

Rheumatoid arthritis is a debilitating autoimmune disease that affects an estimated 1.3 million Americans and hinders daily activities.

The damage that occurs in RA is a result of the immune system attacking joint tissue, causing painful chronic inflammation, irreversible destruction of cartilage, tendons and bones, which often results in disability.

Common RA symptoms include inflammation of the joints, swelling, fatigue, stiffness and pain.  Additionally, since RA is a systemic disease, it can affect other tissues such as the lungs and eyes.

Roche is also the world leader in in-vitro diagnostics, tissue-based cancer diagnostics and a pioneer in diabetes management.

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.

Biogen Idec has products that address diseases such as lymphoma, multiple sclerosis, and rheumatoid arthritis.