Days after a critical TV documentary on the drug, two new large studies have confirmed an increased incidence of death and kidney damage among patients given Bayer’s currently-suspended blood loss agent Trasylol.

The studies, which are published in the latest issue of The New England Journal of Medicine, claim that Trasylol (aprotinin), which reduces bleeding during coronary artery bypass grafting, has been proved as an effective treatment but its safety profile has to be questioned.

The first study, carried out by staff at Brigham and Women's Hospital, Harvard Medical School, analysed data from over 78,000 CABG cases. 33,517 patients received Trasylol and 44,682 were given aminocaproic acid. Overall, 1,512 aprotinin patients (4.5%) and 1,101 aminocaproic acid patients (2.5%) died and the authors noted that after adjustment for 41 variables, Trasylol was associated with a 64% greater risk of death and an increased need for dialysis.

The second study involved data on 10,275 patients who underwent CABG from 1996 to 2005 at Duke University. The study population consisted of 1,343 patients (13.2%) given aprotinin, 6,776 on aminocaproic acid (66.8%), and 2,029 (20%) who had no antifibrinolytic therapy. Lead author Andrew Shaw wrote that the death rate was 32% percent higher among the patients on Trasylol compared to those who received no medication and 27% higher than those on aminocaproic acid. Dr Shaw also noted that in his study, “there does appear to be an association between continued use of aprotinin and reduced kidney function".

The story behind Trasylol is a controversial one. Bayer voluntarily suspended sales in November 2007 after a Canadian study was stopped because of patient deaths and the company is waiting for the release of all the data from that trial which is due soon. However the US Food and Drug Administration has come under severe criticism for letting the drug remain on the market for so long and the 60 Minutes TV programme last Sunday included the claim from a researcher that the lives of 22,000 patients could have been saved if the agency had pulled it two years ago.

The studies are accompanied by an editorial by Wayne Ray of the Vanderbilt University in Nashville. He writes that “the history of aprotinin thus exemplifies the intrinsic limitations of current approaches to evaluation of the comparative efficacy and safety of new medications. Premarketing testing leaves many important questions unanswered because of the frequent reliance on comparison with placebo and the limited numbers of patients studied."

Bayer sued over Kogenate
Meantime, Bayer has been hit by a lawsuit filed in the USA by Novartis and Novo Nordisk who claim that the Leverkusen-headquartered firm’s haemophilia treatment Kogenate infringes their patents.

The plaintiffs are claiming that through the production and distribution of Bayer’s recombinant factor VIII product Kogenate, the company is infringing a compound patent issued in 2006. The suit also includes two haemophilia products sold by Wyeth and CSL Behring.

“Essentially, the plaintiffs claim patent infringement and compensation,” not a court order to suspend sales of Kogenate, said Bayer. The firm added that it will “vigorously defend itself against the complaint” as it is infringing on any valid patent claim of Novartis.

Kogenate is a big earner for the German firm and third-quarter 2007 sales reached 213 million euros, a rise of 7%.