Xolair (omalizumab) is a drug for treating asthma that is brought on by allergies. Approved in 2003, it is an injectable medication for patients aged 12 and older whose asthma symptoms are not responding to inhalable asthma drugs. For patients, it has been shown to decrease the number of allergic asthma attacks, but it has also been shown to have side effects that include adverse heart and brain events.

In 2009, with an initial warning to the public, both the U.S. Food and Drug Administration (FDA) and Health Canada launched investigations of Xolair’s side effects, including heart attacks, heart failure, arrhythmia, fainting and blood clots, in response to findings from a U.S. study. The observational study, called “Evaluating the Clinical Effectiveness and Long-Term Safety in Patients with Moderate to Severe Asthma (EXCELS),” looked at 5,000 asthma patients taking Xolair compared to 2,500 in a control group that did not.

In 2012, upon completion of EXCELS, findings suggested there was a “disproportionate increase in heart problems among Xolair users.” According to the FDA, “The heart and brain blood vessel problems included mini-strokes known as transient ischemic attacks or TIAs; heart attacks; sudden, unexpected chest pain; high blood pressure in the arteries of the lungs called pulmonary hypertension; and blood clots in the lungs and veins.”

The FDA conducted further evaluation of the heart and brain risks noted in the five-year safety study. They reviewed “a combined analysis of 25 randomized double-blind clinical trials comparing Xolair to a placebo.” No increased problem from Xolair was noted in this study, “but the low number of these events, the young patient population, and the short duration of follow-up” prevented the FDA from saying there wasn’t a risk.

Warning Label

Marketed by Roche in the United States, and Novartis in Canada, Xolair’s past “black box” warning only covered the threat of anaphylaxis. An anaphylactic reaction, typically a severe allergic reaction, typically involves swelling of the mouth and throat, trouble breathing, dizziness, itching, and hives. The danger is that while some cases of anaphylaxis can happen after the first dose, it is possible to take Xolair for more than a year before such a reaction occurs. However, this label was updated with the FDA’s findings.

As a result of the FDA review of the safety study and of its combined clinical trials, information about the potential risks of heart- and brain-related problems were added to the Adverse Reactions section of Xolair’s package insert. Moreover, other clinical trials showed slightly higher rates of various cancers in patients treated with Xolair compared with those not taking the drug, so the possible risk of cancer was also added to the label.

Despite the additional warnings, the FDA approved Xolair (indicated for allergic asthma) in the United States for an additional indication — treatment of chronic idiopathic urticaria (also called CIU, an autoimmune reaction in which hives last for weeks at a time).