Lilly's Xigris will be first drug ever launched for sepsis. Its high cost is creating shock waves among hospitals
The Food & Drug Administration has approved the first drug indicated to treat sepsis: Xigris (drotrecogin alfa [activated], Eli Lilly & Co.). Hospitals will get the drug through their regular wholesalers, said a Lilly spokeswoman, but Syncor will be able to deliver an emergency supply of Xigris to almost any institution in the country within three hours.
How useful Xigris will be is an open question. An FDA advisory committee split 10 to 10 on recommending approval. The panel was concerned about the high incidence of severe bleeding in patients who received Xigris and the exclusion of the most acutely ill patients from the PROWESS trial supporting efficacy and safety.
Sepsis affects 750,000 patients annually in the United States and kills 215,000, according to Lilly. The condition is a cascade of inflammatory and hemostatic abnormalities that can result in massive clotting, massive bleeding, multiple organ failures, and death. It is usually triggered by infection or trauma to the body. Xigris, a recombinant human protein C, is the first drug that successfully blocks the sepsis cascade.
The product is no panacea, said David Foster, research fellow and clinical instructor at the University of Michigan College of Pharmacy. The risk of severe bleeding was 3.6% versus 2% for placebo. There are no data showing favorable clinical outcomes beyond the initial 28 days and no data regarding length of patient stay or discharge. "But until now, all we had for sepsis was supportive therapy," Foster said. "Now that we have the first effective treatment, clinicians are excited, very excited."
The best news is that Xigris showed a 20% relative survival advantage over placebo over the first 28 days after treatment. The good news is that it provided a 6% absolute increase in survival compared with conventional treatment. The bad news is the cost.
"It is going to be a very interesting product, to say the least," said Douglas Fish, associate professor of pharmacy practice at the University of Colorado School of Pharmacy. "This will be the first product actually labeled for sepsis. There is going to be tremendous pressure to use it, but there will also be many hospitals that can't afford to stock this drug. It's Catch-22 for hospital pharmacies." Before Xigris was approved, pharmaceutical consultant Decision Resources predicted the cost would fall between $5,000 and $10,000 per treatment. When the drug was approved last month, Lilly said the price would average $6,800, depending on patient weight and acuity.
At $6,800 per treatment, the average 250- to 300-bed hospital could spend $1.4 million to $2 million annually on Xigris. That assumes that all 200 to 300 generalized sepsis patients that most hospitals see annually receive the new drug. "When your total drug spend is in the range of $4 or $5 million, you can't take that kind of budget hit," warned Daniel Albrant, president of Pharmacy Dynamics. "The benefit of the drug is modest, even if it performs as well in practice as it did in clinical trialswhich most drugs do not. I'm advising my clients not to be in a rush to order this product."
The FDA also seems cautious. Xigris was approved for reduction of mortality in adults with severe sepsis (associated with acute organ dysfunction) with a high risk of death. Contraindications include active internal bleeding; hemorrhagic stroke within the past three months; intracranial or intraspinal surgery or severe head trauma within the past two months; trauma associated with increased risk of life-threatening bleeding; epidural catheterization; and intracranial neoplasm, mass lesion, or evidence of cerebral herniation.
Prescribing information also contains a long list of warnings related to bleeding, the most common severe side effect associated with Xigris. Lilly also cautioned that efficacy has not been established in adults with lower risk of death, and the drug has not been studied in children. Both patient groups will be studied in post-approval trials, the company said.
Lilly would like to see Xigris become the standard of care for sepsis. It could happen, Foster said, but not soon. "I expect the same mindset we saw with tPA [tissue plasminogen activator] in stroke," he said. "People will be very cautious until we know a lot more about this drug. [Profiles of] patients who survive with Xigris look very much like [those of] patients who die. We don't know the difference yet."
An average course of treatment for Xigris will cost about $6,800. Observers expect Lilly to launch a patient assistance program (PAP) for indigent patients. But PAPs typically help only a small minority of patients who can't afford drug therapy. Hospitals bear the brunt of unreimbursed inpatient drug costs.
What is clear is that Xigris has the potential to bankrupt hospital pharmacy budgets, with a medication that is suddenly going to eat up 20%-25% of the drug budget, warned Pharmacy Dynamics president Daniel Albrant. "No other drug has ever taken that big a bite."
Long term, the best solution may be a new diagnosis-related group (DRG) for severe sepsis. Lilly is already talking with federal officials about a sepsis-specific DRG, a com-pany spokeswoman said.
"Everybody is applauding Lilly's efforts to champion a new DRG," said Maureen Smythe, professor of pharmacy practice at Wayne State University in Detroit and a critical care pharmacist at William Beaumont Hospital. "We don't know how successful they will be, but we hope they are. The cost of Xigris exceeds that of current DRGs."
Until and unless a new DRG appears, Albrant is advising his hospital clients to treat Xigris as a capital expenditure, not a drug purchase. The annual cost of treatment is comparable to a medical machine, he said. That makes review and prior authorization by the medical executive committee a reasonable step.
Other hospitals are planning to treat Xigris as a drug purchase but limit their financial exposure with utilization controls. Narrow indications help hospitals restrict the drug to patients judged most likely to benefit, said Douglas Fish, associate professor of pharmacy practice at the University of Colorado School of Pharmacy.
Other institutions had restricted Xigris even before the product was approved. The University Hospitals of Cleveland at Case Western Reserve University put Xigris on prior approval status in early November, said assistant director of pharmacy services Ron Cowan. Use will be approved only for patients who meet the PROWESS inclusion restrictions and have at least two organ failures.
"Limited approval to use certain drugs is normal at this hospital," Cowan said. "Xigris is just one more product that requires prior approval from a very limited number of practitioners for a small subset of patients."
Fred Gebhart. Hospitals brace for launch of first-ever sepsis drug. Drug Topics 2002;1:24.