New Jersey-based pharmaceutical firm Johnson & Johnson may not get FDA approval this week for a rheumatoid arthritis treatment the company had hoped would successfully compete with Actemra, a drug implicated in hundreds of deaths as well as respiratory infections and cardiac arrest. It turns out that the new drug, known as sirukumab, has similar issues. According to data from the clinical trial, more patients taking the experimental medication died than those who were given placebos.
Sirukumab, which was to have been marketed under the brand name Plivensia, was developed by Johnson & Johnson in partnership with Glaxo-Smith Kline. In June 2016, GSK announced that its Phase III trial, SIRROUND-D, had successfully met the co-primary endpoints – meaning that the researchers had collected sufficient evidence of the new drug’s effectiveness in treating the target population.
In this case, that population consisted of patients suffering from rheumatoid arthritis (also known as “giant cell arthritis”) whose condition had failed to respond to other treatments. Such medications work by blocking a cell-signaling protein, or cytokine, known as interleukin-6 (IL-6), which is a contributory factor in the inflammation associated with the disease.
The bad news came after an analysis of the data by staff reviewers at the FDA. That analysis revealed a higher death rate among subjects who were given sirukumab than among the control group who received placebos. The report was published at the end of July – only two days before the meeting of an advisers committee to decide whether or not the new prescription drug should be granted FDA approval.
According to the report, most patients in the study who died suffered cardiac events and infections – which have also been side effects associated with Actemra. In addition, subjects who took sirikumab experienced other problems involved with immune function suppression that were found in similar drugs. However, the overall mortality rate among subjects “seems unique to the sirukumab program,” according to the report. Subjects also developed malignant tumors, which has not been the case with Actemra and other IL-6 inhibitors.
GSK has announced that it would end the sirukumab program and relinquish all rights to the drug to partner J&J. Despite the bad news this week, there is still a chance that such approval may be granted. Although the FDA usually heeds the adviser committee’s recommendations, the federal regulatory agency is under no obligation to do so. However, analysts believe that even if it sirukumab is approved, the differences between it and Actemra are not enough to make a difference in the current market for IL-6 inhibitors.
Meanwhile, despite the problems revealed during the Phase III trial, as well as pending litigation over Actemra, Johnson & Johnson is confident in its new product. A company spokesman points out that because of the complexity of the disease, a patient suffering from rheumatoid arthritis must often go through a series of different treatments before finding one that is effective for his or her condition. Brian Kenney, J&J’s Senior Director of Pharmaceutical Communication & Public Affairs, said, “We are confident in the benefit-to-risk of sirukumab.”