By Brady Huggett
It might be fitting to call Chiron Corp.¿s sepsis product, Tifacogin, another dead soldier ¿ one more attempt to fight the good fight against sepsis that came up short. But even after revealing that the Phase III Optimist trial did not meet its primary endpoint, the company said the final decision concerning Tifacogin (that is, whether it¿s dead or alive) would come after a full analysis of data.
¿We are in the course of analyzing the data and we will certainly have a better understanding when we complete the analysis,¿ said John Gallagher, media relations manager at Chiron. ¿At the moment all we are saying is that we didn¿t meet the primary endpoint. We aren¿t making any decisions about the product until we analyze the data.¿
Although the trial raised no safety issues, results indicated that Tifacogin did not meet the primary endpoint of reducing 28-day all-cause mortality. The double-blind, placebo-controlled trial involved about 2,000 patients with severe sepsis from 16 countries. Chiron is developing the product with its partner, Pharmacia Corp., of Peapack, N.J.
Chiron, of Emeryville, Calif., can perhaps find solace in the fact that others have failed at developing a successful treatment for sepsis: Immunex Corp., of Seattle; Celltech Group plc, of Slough, UK; Synergen Inc., of Boulder, Colo.; Cortech Inc., of Denver; and Xoma Corp., of Berkeley, Calif., all had products felled by the indication, among others.
Just last month Eli Lilly and Co., of Indianapolis, and its sepsis product, Xigris, officially received a deadlocked 10-to-10 vote from the Anti-Infective Drugs Advisory Committee on whether the drug was safe and effective. And while Lilly said it was ¿shocked¿ by the vote, days later the FDA sent Lilly an ¿approvable¿ letter for the drug, giving the company hope that the product will eventually receive the full FDA nod. (See BioWorld Today, Oct. 17, 2001; and Oct. 30, 2001.)
Chiron knows well the pitfalls that surround the indication.
¿There is a cascade of events that are involved in sepsis,¿ Gallagher said. ¿It¿s a tricky syndrome to understand.¿
Sepsis is a spectrum of clinical conditions caused by the immune response to infection or trauma and characterized by systemic inflammation and coagulationn ¿ coagulation that can cause multiple-organ failure. Thirty percent to 50 percent of the people that develop sepsis die from the disease. Tifacogin is a recombinant form of tissue factor pathway inhibitor (TFPI), which is produced in the body and works to inhibit a key step in the blood coagulation process that is part of the formation of clots. Through the blocking of clot formation, TFPI is believed to lead to the prevention of multiple-organ failure.
Pharmacia and Chiron became partners on Tifacogin through a series of transactions that began with Chiron signing with Monsanto Co.¿s subsidiary G.D. Searle & Co, Gallagher said. When Pharmacia merged with Monsanto, Pharmacia also took on Tifacogin. The deal is structured so that the companies share equally in both funding development and profits, Gallagher said.
Gallagher said Chiron learned ¿some valuable skills¿ from the trial that will ¿come in handy¿ as Chiron continues to push products through development.
Its biopharmaceutical pipeline boasts several products for various indications in Phase I, II or III development, including PA 1806 for Gram-negative lung infections in cystic fibrosis patients in a Phase I trial and Proleukin for HIV infection in a Phase III study. Its marketed products in the United States and Europe include Betaseron for multiple sclerosis, Proleukin for metastatic melanoma and metastatic renal cell carcinoma, and Regranex gel for diabetic foot ulcers.
Chiron posted net product sales for its biopharmaceuticals division of $86 million in the third quarter, an increase of 42 percent from 2000¿s third-quarter biopharmaceutical revenue of $60 million. However, Chiron also draws revenue from its vaccines division and its blood-testing services, bringing its total revenue for 2001¿s third quarter to $302 million. With such far-reaching financial sources, the blow of a failed Phase III trial is softened, Gallagher said.
¿We have a unique business model; we have revenue from our three sections,¿ he said. ¿Our success isn¿t dependent on any one program.¿
On top of that, Chiron is profitable and, as of Sept. 30, was sitting on a $631 million heap of cash and short-term investments, further proof that Chiron is on firm earth.
¿We have a large cash reserve, we continue to meet or beat [Wall Street] estimates and have for the past 13 quarters,¿ Gallagher said. ¿We are a very solid company.¿
Chiron¿s stock (NASDAQ:CHIR) fell $4.50 Wednesday to close at $45.59.