The analysis of 67 clinical trials found no association between omalizumab treatment and risk of malignancy. A causal relationship between omalizumab therapy and malignancy is “unlikely,” the researchers conclude in a report online February 24 in the Journal of Allergy and Clinical Immunology.
“The data are reassuring,” first author Dr. William W. Busse, Professor of Medicine, Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin Medical School in Madison, noted in an email to Reuters Health.
Omalizumab is a humanized anti-IgE monoclonal antibody approved as an add-on therapy for the treatment of inadequately controlled severe persistent allergic (IgE-mediated) asthma in adults, adolescents, and children (≥6 years of age) in Europe, and in adults and adolescents (≥12 years of age) with moderate-to-severe persistent allergic asthma in the United States.
An initial analysis of pooled data from phase I to III studies of omalizumab showed a numeric imbalance in malignancies arising in people who got omalizumab (0.5%) compared with those who did not (0.2%). These findings are reflected in both the European Union and US labels for omalizumab.
“The difference did not achieve statistical significance and probably related to twice as many patients receiving omalizumab as placebo,” said Dr. Busse, who worked on the initial pooled analysis. “Nonetheless, this raised concerns with a new product even though the biology of IgE and the monoclonal did not suggest a mechanism for an increased rate for cancers,” he said.
To revisit the issue, Dr. Busse and colleagues conducted an updated pooled analysis including data from 67 phase I to IV clinical trials, including 32 randomized, double-blind, placebo-controlled trials. The trials involved 11,459 subjects (7,789 treated with omalizumab).
The primary analysis, which assessed the incidence of primary malignancy in the 32 randomized double-blind placebo-controlled trials, identified malignancies in 25 patients – 14 in 4,254 omalizumab-treated patients and 11 in 3,178 placebo-treated patients.
The incidence rates per 1,000 patient-years of observation time for omalizumab- and placebo-treated patients were not significantly different (4.14 and 4.45, respectively; difference in rates: -0.31, rate ratio=0.93).
The primary malignancies identified were of varying histologic type and occurred in a number of different organ systems. There was no cancer cluster. The fact that the types of cancers noted were diverse makes a cause and effect relationship “unlikely,” Dr. Busse told Reuters Health.
“Now, with the increased numbers of treated patients available for evaluation, it is reassuring to find safety with this product. This is especially true as younger patients, down to 12 years of age, receive this as an asthma treatment,” he added.
The researchers say additional long-term safety data on omalizumab will come from the 5-year EXCELS study, which will specifically look at the incidence of all malignant tumors and other serious adverse events reported in more than 7,000 patients with moderate-to-severe persistent allergic asthma in a real-world clinical setting.
An interim analysis of EXCELS data comprising 18,860 patient-years in the omalizumab-treated group and 10,947 patient-years in the non-omalizumab-treated treated group showed similar malignancy incidence rates in the two groups (rate ratio 0.88). Final results of the EXCELS study are expected later this year.
The current analysis was supported Novartis Pharma AG and Genentech. Dr. Busse has consultant agreements with Novartis and Genentech. A complete list of author disclosures can be found with the original article.