Last fall, when Biogen Idec Inc. and partner Swedish Orphan Biovitrum (Sobi) made public the Phase III from A-LONG, a trial testing their long-lasting recombinant factor VIII candidate – since branded Eloctate – in hemophilia A, most analysts were pleased but cautious about the treatment's chances anytime soon to dominate Advate, marketed by Baxter Healthcare Corp.

More results, just disclosed from the same study, have not changed the picture.

"Given the need for more than once-weekly dosing to optimize bleeding rates for the majority of patients (as we expected), we would not anticipate [Eloctate] to upend the treatment paradigm overnight," wrote Wells Fargo analyst Brian Abrahams, on the heels of the first A-LONG data. (See BioWorld Today, Nov. 7, 2012.)

Mark Schoenebaum, analyst with ISI Group, told BioWorld Today he found "nothing materially new" in the added results, made public in five platform and oral presentations at the International Society on Thrombosis and Hemostasis Congress in Amsterdam, the Netherlands.

For the first time, hemostasis assays showed that despite differences between patients in thrombin generation, Eloctate and Advate, from Deerfield, Ill.-based Baxter, showed equivalent thrombin generation potential post-infusion. Eloctate's thrombin-making mojo lasted longer, too.

In the treatment of acute bleeding episodes across the prophylaxis and episodic treatment arms, 87 percent of bleeds were controlled with a single injection of Eloctate, and more than 97 percent were controlled with two or fewer injections.

The main selling point with Eloctate is still dosing frequency. Top-line results last year showed that in the individualized prophylaxis arm, the median dosing interval was 3.5 days, beating Advate, with its labeled dosing frequency of three to four times per week. And during the last three months on study, 30 percent of patients in that arm reached a mean dosing interval of five days.

And the stickler, Schoenebaum said, is still safety – not necessarily Eloctate's lack, but hemophilia patients' concern. "Over the long term, long-acting therapies will take majority share," he said.

"But it will take many years for this market to convert. These patients live in mortal fear of [developing] inhibitors. It will take years of real-world experience to 'prove' that long-acting drugs are really as safe as the short-acting" therapies, such as Advate, Schoenebaum noted.

Earlier data showed Eloctate controlled bleeding episodes in 98 percent of patients with one or two injections, and no patients turned up with inhibitors. The median annualized bleeding rates, including spontaneous and traumatic bleeds, totaled 1 .6 in the individualized prophylaxis, 3.6 in weekly prophylaxis and 33.6 in on-demand treatment.

A hemophilia market analysis report by Morningstar in January noted the "very low switch rate" among therapies for the disease, less than 10 percent.

"Many patients have been on products like Baxter's Recombinate or Bayer's Kogenate for more than a decade," the report pointed out. "We think Recombinate illustrates patient loyalty to their chosen therapy, when incremental improvements are not significant. While conversion from plasma-derived factor VIII to Recombinate was quite rapid, conversion from Recombinate to [next-generation] Advate has been a much longer process."

Patients pleased with Recombinate stayed with it, though newly diagnosed ones, many of them children, were put on Advate. "In the U.S., after almost 10 years of Advate marketing, Recombinate still comprises about 25 percent of Baxter's recombinant factor VIII sales," Morningstar found.

The $5.2 billion market for hemophilia A therapies could reach $7 billion by 2016, which means a 6 percent average growth rate over the next five years, according to Morningstar.

Though Leverkusen, Germany-based Bayer AG and Baxter hold sway over the space with recombinant versions of the factor VIII protein, Biogen and Bagsvaerd, Denmark-based Novo Nordisk A/S are likely to break through with approvals starting early next year.

More use of hemophilia therapy for prophylaxis likely will drive growth. As patients get older they tend to comply less, and many of them aren't familiar with the idea anyway, since it did not become prevalent as an option until the 1990s. Prophylaxis levels among 18-year-olds are estimated around 80 percent. After age 40, the level stands at about 20 percent. Sales of hemophilia drugs for prophylaxis hover in the 65 to 75 percent range.

Baxter, with Advate, will not give up without a fight. At the same meeting where Weston, Mass.-based Biogen and Sobi, of Stockholm, Sweden, updated their Phase III results, Baxter offered Advate data from a pair of studies that showed a link between peak levels of factor VIII in the body and efficacy (suggesting that peaks may be important when selecting a therapy) and that efficacy via reducing bleeds "considerably" outweighs infusion convenience as the treatment priority.