The drug's maker, Genentech, was told to update the product labellingby US drugs watchdog the Food and Drug Administration (FDA), following reports of anaphylaxis in patients taking Xolair. Also, a new medication guide is now to be issued to every patient given Xolair, informing themof this life-threatening risk.
Xolair (omalizumab), given as an injection, was approved for use in the US in June 2003 to treat patients who are at least 12 years old and who have moderate-to-severe persistent allergic asthma that doesn't respond to inhaled corticosteroids.
The drug is now also licensed in Australia, Brazil and Canada. In the UK, the National Institute for Health & Clinical Excellence (NICE) has recently given provisional approval for its use in England, Wales and Northern Ireland.
Xolair is a monoclonal antibody, a type of genetically engineered protein that blocks the action of immunoglob-ulin E (IgE), involved in allergic and asthma attacks. While many drugs attempt to blunt an attack once it has begun, Xolair is designed to prevent such attacks from starting at all-and it does. In clinical trials, those taking the drug had fewer asthma attacks, and were also able to reduce or eliminate their use of inhaled corticosteriods, which can have long-term side-effects (J Allergy Clin Immunol, 2001; 108: 184-90).
However, patients who take this new 'wonder drug' may be putting their lives at risk.
According to Genentech's own trials, about one in 1000 patients (0.1 per cent) will develop anaphylaxis with Xolair. And reports continue to linkthe drug with severe allergic reactions. Based on the 57,300 patients treated with Xolair from June 2003 to Decem-ber 2006, the frequency of anaphylaxis is estimated to be at least 0.2 per cent. But because adverse reactions are reported voluntarily, the actual percentage could be higher.
More worrying, anaphylaxis may not present straightaway, but up to four days after first taking the drug or even more than a year after starting regular treatment. It can also affect patients who had no allergic reactions to the drug in the past.
Signs and symptoms to look out for include breathing difficulties, chest tightness, dizziness, fainting, itching and hives, and swelling of the mouth and throat. Patients are advised to seek emergency medical treatment as soon as any of these symptoms arises.
However, the risk of life-threatening hypersensitivity to the drug is not the patient's only concern: IgE may be important for immune function (Eur J Immunol, 2003; 33: 1030-40), so Xolair-by blocking IgE-may cause unexpected problems. Genentech's own clinical trials showed that Xolair patients had significantly increased chances (0.5 per cent) of developing cancer, including those of the breast, skin and prostate.
IgE may also be a natural defence against parasites, so Xolair may be increasing the risk of infestations in high-risk groups. In a year-long trial in Brazil, Xolair patients were twice as likely to be infected with roundworm, hookworm, whipworm and threadworm, compared with those given a placebo.
It's also possible that Xolair can cause nasal polyps, adrenal insuf-ficiency and Churg-Strauss syndrome, a condition that affects blood vessels (systemic necrotizing vasculitis), the lungs, nerves and skin-and ironically, can also lead to severe asthma (N EnglJ Med, 2006; 355: 1281-2).
Most important of all, none of the clinical trials with Xolair lasted for more than a year, so no one really knows what the long-term impact of the drug will be on patients' health.
The future for Xolair
This is not the first asthma drug to be slapped with a black-box warning, the most severe caution that the FDA can give for a prescription drug. In 2005, drug giant GlaxoSmithKline (GSK) was instructed to revise the label warnings for Advair and Serevent, two of the most popular asthma medications, following the discovery that they can increase the risk of severe asthma attacks and even death. Several other long-acting bronchodilator medica-tions have since also been given a black-box warning.
Nevertheless, for GSK, that was merely a minor setback. In the two years since the warning, demand for Advair has actually increased by 12 per cent. Similarly, although Xolair has now been shown to be a potentially lethal injection, it's believed that the new black-box warning is unlikely to have a detrimental impact on sales.
For alternative ways to beat asthma, consult WDDTY's Asthma Manual (lb29.95).
- Injection-site reactions such as pain, bruising, redness, burning and inflammation
- Viral infections
- Upper respiratory tract infections
- Pruritus (itching)
- Joint pain.