Shocking! Lilly Pulls Xigris Drug After Study Fails

Shocking! Lilly Pulls Xigris Drug After Study Fails

October 26th, 2011 // 12:22 pm @ jmpickett

In the latest setback for Eli Lilly, the drugmaker is withdrawing its 10-year-old Xigris treatment for septic shock after a study found the medication failed to help patients live longer in a clinical trial. Specifically, the study did not find a statistically significant reduction in 28-day all-cause mortality in patients with septic shock.

The study, known as Prowess-Shock, had begun in March 2008 as a condition for continued market authorization in Europe, where Xigris was approved in 2002; the FDA approved the drug the year before. To satisfy regulators, Lilly ran a new placebo-controlled clinical trial to confirm the risks and benefits. (You can read an interim progress report from the European Medicines Agency here).

The results found a small difference in mortality – 26.4 percent in the Xigris arm versus 24.2 percent in the placebo arm; there were 1,680 patients. And the risk of severe bleeding events, which is the main risk with the drug, was 1.2 percent in the Xigris arm and 1 percent in the placebo arm, suggesting there was no increased harm, according to the European Medicines Agency (see this).

“While there were no new safety findings, the study failed to demonstrate that Xigris improved patient survival and thus calls into question the benefit-risk profile of Xigris and its continued use,” Tim Garnett, Lilly’s senior vp and chief medical officer, in a statement. “We believe the original Xigris approval was appropriate and these recent results were quite unexpected. A contributing factor to these study results could be advances in the standard of care for treating severe sepsis over the past 10 years.”

However, Xigris has been troublesome from the start. Initially, the drugmaker described the medication, which acts within blood vessels to treat severe sepsis, as one of six new ‘growth drivers.’ But almost immediately, former Lilly ceo Sid Taurel was acknowledging difficulties. In the 2002 annual report, he is quoted as saying that sales were “slower than expected, weighed down by a narrow label and prescriber caution…We saw it would take considerably more time, effort, and investment to deliver the full promise of Xigris.”

Why? An FDA advisory committee wanted another confirmatory trial conducted because of concerns over increased risk of serious bleeding, and the agency later decided that Lilly had to perform additional testing in selected subgroups. Along with high pricing, the threat of bleeding dampened enthusiasm among doctors for using the medication. At the time of approval, standard treatments for sepsis typically cost less than $50 per day, while Xigris cost $6,800 for each treatment, although that price later rose.

To fight back, Lilly hired a public relations firm to create concerns about rationing and that physicians were being “systematically forced” to decide who would live and who would die, as a perspective piece in The New England Journal of Medicine noted. The drugmaker also gave a $1.8 million grant to a group of doctors and bioethicists to form the Values, Ethics, and Rationing in Critical Care Task Force to examine rationing issues. And there was the Surviving Sepsis Campaign to raise awareness of severe sepsis and develop treatment guidelines.

With the help of its pr firm, Lilly introduced SSC in 2002 at the European Society of Intensive Care Medicine and the next year, gathered experts in critical care and infectious diseases to create guidelines for sepsis management, which were later published in Critical Care Medicine and touted Xigris over older options, although clinical trials had never been conducted, according to the NEJM piece. Meanwhile, Lilly provided almost all of the funding and many participants had financial or other relationships with the drugmaker.

At the end of the day, Lilly was exposed for surreptitiously creating concern about rationing and also controlling the creation of treatment guidelines that were skewed in its favor. “The challenges involved in producing first-rate guidelines and performance standards are only exacerbated by the intrusion of marketing strategies masquerading as evidence-based medicine,” according to the NEJM authors, who were senior investigators at the critical care medicine department at the National Institutes of Health.

And so, for the past decade, patients have been treated with an expensive drug that was really no more effective than a placebo, while less expensive treatments were available. But Lilly needed replacement products for the Prozac antidepressant, which had lost patent protection, and embarked on the sort of marketing campaign that has generated scorn and derision toward the pharmaceutical industry. Such efforts have required treatment for a different sort of shock. Meanwhile, Xigris may now be gone, but the memories linger.

Source: Pharmalot