Roche halts ocrelizumab trials

Rheumatoid arthritis starts with inflammation of the lining of the joint and is followed by destruction of the underlying cartilage, and then the bone itself (Roche)

The future of Roche and Biogen Idec’s rheumatoid arthritis drug ocrelizumab has been thrown into doubt after the manufacturers decided to suspend its development.

The companies put their programme on hold after fears were raised about the safety of patients participating in the trials.

An independent body called the Ocrelizumab RA & Lupus Data and Safety Monitoring Board (DSMB) looked at four rheumatoid arthritis (RA) studies (SCRIPT, FEATURE, FILM and STAGE) and two in lupus (BELONG and BEGIN).

After reviewing these the DSMB decided that risks to patient safety outweighed the benefits “observed in these specific patient populations at this time”.

“Patient safety is of the utmost importance in all of our drug development programmes,” said Hal Barron, chief medical officer at Roche.

“In light of the DSMB recommendations we have decided to suspend ocrelizumab treatment in the RA clinical development programme.”

The DSMB had worries over serious and opportunistic infections, some of them fatal. The companies say they will look again at all data before making a final decision on the future of ocrelizumab.

Alarm bells had sounded earlier when two of the six studies were stopped: FILM, which looked at MTX-naive RA patients, and BELONG, which took in lupus nephritis patients.

FILM, as well as SCRIPT (for patients who inadequately responded to one or more TNF antagonists) remain blinded.

Ocrelizumab is an investigational humanised monoclonal antibody that selectively binds to the CD20 antigen protein on the surface of B-cells.

It then interacts with the body’s own immune system to eliminate CD20-positive B-cells, allowing healthy B-cells to regenerate.

RA is a crowded therapy area, where Roche’s own RoActemra (tocilizumab) and MabThera (rituximab) already vye with drugs such as Merck & Co’s Remicade (infliximab), Abbott’s Humira (adalimumab) and Pfizer’s Enbrel (etanercept) for a piece of the market.

Despite its problems in RA, ocrelizumab is currently in phase II trials for relapsing remitting multiple sclerosis (RRMS).

Last December it showed a statistically significant reduction in signs of disease activity as measured by brain lesions versus placebo.