TOKYO, Japan—Actemra® (tocilizumab), the first humanized interleukin-6 receptor-inhibiting monoclonal antibody used to treat rheumatoid arthritis (RA), is suspected of causing 15 deaths and 221 serious adverse reactions in the nearly 5,000 Japanese patients treated since the drug was approved in April 2008.

Masayuki Yamada, a spokesman from Roche's Japanese unit, Chugai Pharmaceutical, said in a prepared statement, "The fact that the causal relationship was not denied means there is a possibility that Actemra may have had an impact." However, the company maintained that similar 0.3% mortality rates had been seen in clinical trials of other biologicals used to treat RA.

Actemra deaths from heart attack, stroke

Thirteen of the 15 deaths were in patients 60 or older and were from heart attacks, heart failure, or cerebrovascular accidents. Tocilizumab has been linked to increased cholesterol levels, to liver function abnormalities, and to gastrointestinal problems.

Company spokesman Hiroshi Araki said later that the rate of 15 deaths among 4,915 people in Japan taking Actemra for rheumatoid arthritis in the 10 months ending February 15 is the same level as was seen in clinical trials and is similar to mortality rates for competing products.

Actemra was approved for RA in April 2008 in Japan and in January 2009 in Germany, France, and the U.K.  Chugai has sold the drug in Japan since 2005 for Castlemans disease. It had been seen as a potential blockbuster for Roche.

Actemra still on hold in US

US FDA approval of Actemra was put on hold in December, and the agency asked Roche for additional safety tests in animals to determine effects on pregnancy and fertility. Last July an FDA advisory panel had recommended that the approved dose be halved, or that use be limited to patients who do not respond to TNF inhibitors until Roche completes a planned safety review. The FDA asked Roche to provide a Risk Evaluation and Mitigation strategy for Actemra to support safe prescribing and make sure patients understand risks and benefits of using the drug.

Chugai shares fell 5.9% and Roche shares fell 1.2% on the news from Japan.