Betrixaban, which Merck is developing through a licensing deal it recently struck with privately held Portola Pharmaceuticals, led to a lower incidence of serious bleeding than warfarin at 40 milligrams, the lowest of the tested doses.
At 80 mg and 60 mg, the risk for serious bleeding appeared to be comparable to warfarin, according to data presented on Monday at the American College of Cardiology scientific meeting in Atlanta.
The profile of the drug is very interesting and the preliminary results look promising, but would have to be validated by a very large Phase III trial, said Dr. Michael Ezekowitz, who presented data from the 508-patient study.
The safety profile looks good. We're very sensitive to inducing liver dysfunction and there's no evidence so far that this drug is toxic to the liver, said Ezekowitz, vice president of the Lankanau Institute for Medical Research outside of Philadelphia.
Betrixaban belongs to a new class of blood clot preventers called factor Xa inhibitors that are being developed by several drugmakers, including Bayer, Bristol-Myers Squibb Co in partnership with Pfizer Inc, and Boehringer Ingelheim.
While Merck is well behind rivals, analysts have suggested its once-a-day pill could prove to be the best-in-class of the drugs that hope to replace the effective but difficult to use warfarin.
One differentiating factor is that unlike rival factor Xa drugs, betrixaban is not cleared by the kidneys.
That means it can be used in patients with advanced kidney disease. Other drugs' trials have excluded these patients, Ezekowitz said.
The drug is also metabolized differently, which could lead to fewer harmful interactions with other drugs, he explained.
Patients in the Phase II study were an average age of 74 and all suffered from atrial fibrillation -- a dangerously irregular heart beat that significantly increases the risk of stroke -- and had at least one additional risk factor for stroke, such as diabetes or obesity.
Atrial fibrillation patients are seen as the largest potential market for these new blood thinners, most of which are also being tested to prevent blood clots following knee replacement procedures.
Oral antithrombotics, in particular the Factor Xa and direct thrombin inhibitors, are potentially one of the largest new emerging drug classes, Jefferies analysts said in a research note. We estimate that the total market for these drugs could be in excess of $18 billion, with the stroke prevention in atrial fibrillation.
The main goal of the study was measuring occurrence of major bleeding or clinically relevant non-major bleeding, as dangerous bleeding is the most significant drawback of all effective blood thinners.
The rates of such bleeding requiring medical attention was 0.8 percent at 40 mg of betrixaban compared with 5.5 percent with warfarin. At 60 mg and 80 mg of betrixaban, the rate was 3.9 percent, which researchers characterized as comparable to warfarin.
After a follow-up of three to 12 months, only one patient in the 40 mg betrixaban group had had a bleeding incident requiring medical care compared with four in the warfarin group. There were 127 patients in each of the four groups.
Merck said it has not yet decided which doses it will move forward into large, Phase III trials. Based on this data, however, the 40 mg dose appears to be a very strong candidate.
Researchers and drugmakers have been searching for decades for an alternative to warfarin, which requires close monitoring and frequent dose adjustments to prevent serious bleeding due to the narrow window between an effective or harmful dose.
Due to food and drug interactions, warfarin, sold under the brand name Coumadin, also requires dietary and lifestyle changes, leading many patients to refuse to take the drug, heightening their risk of stroke.
I'm confident that it will be replaced, Ezekowitz said.