Bayer closes the gap on Biogen’s haemophilia candidate

It was fortunate for Bayer that rival Biogen Idec's attempt to gain US approval of its long-acting haemophilia A product was delayed. Phase III data showing that Bayer's pegylated factor VIII BAY 94-9027 can protect patients from bleeding when infused as infrequently as once a week ought to get specialists talking about this option before Biogen launches its twice weekly candidate Eloctate – even though Eloctate is likely to beat '9027 to market by at least a year.

Patients receiving prophylactic doses of '9027 every two, five or seven days had lower bleeding rates than those receiving on-demand treatment, although little in the way of statistical analysis was released. More data should be revealed at the World Federation of Haemophilia in Melbourne in May, enabling specialists to judge the realistic dosing interval of ‘9027 as well as weigh Bayer’s pegylation strategy against Biogen’s fusion protein.

Preventing bleeds

Bayer already has a player in haemophilia A – Kogenate, which is second only to Baxter International’s Advate in the battle for market share. Haemophilia A, caused by a lack of the clotting factor VIII that is most often caused by a genetically linked mutation, is a mature space, with Advate’s sales shrinking and Kogenate’s plateauing at about $1.5bn. The main source of growth is Novo Nordisk's NovoSeven, used as a rescue treatment for patients who have developed inhibitors to factor VIII.

Therapy has changed in haemophilia, with coagulation factors being infused prophylactically to prevent bleeding rather than as a treatment of bleeding once it begins (Therapeutic focus - Long-acting haemophilia agents set to shake things up, July 26, 2011). Plasma-derived and recombinant factor VIIIs have a short half-life, however; Advate, the first to receive the OK for prophylaxis, is dosed every other day, although response-guided therapy that allows for dosing every third day is allowed if it keeps patients’ trough coagulation factors at least at 1%.

However, given that central IV lines are needed in many cases to aid repeated infusions, any move to reduce the frequency would be welcomed by physicians and patients alike, perhaps as seldom as once a week – thus the race to put a long-acting alternative on the market.

Minor stumble

Biogen has lead the field, generating pivotal data in late 2012 and submitting its NDA a year ago. First mover advantage looks increasingly likely despite a delay in the FDA action date over “validation of certain steps in the manufacturing process,” as chief executive George Scagnos described in October, pushed the expected launch into mid-year.

This minor stumble does, however, give Bayer a chance to gain back precious time. The group gave tantalising hope of once-a-week dosing, but there will be a careful weighing of bleeding rates by specialists once the data are more fully detailed.

The median number of bleeds per person per year was 3.9 in the once-a-week group, compared with 1.9 in the five-day dosing group. Patients who were enrolled in an every-other-day dose group based on their high bleeding rates during assessment saw their bleeds drop from 17.4 per person per year to 4.1, while an on-demand treatment group saw a median 23 bleeds per person per year.

Investigators reported two cases of hypersensitivity, one of which resolved without medical intervention. Given that both Advate and Kogenate labels include warnings of anaphylaxis, this will probably not be a hurdle to approval, but greater detail on the safety profile would be welcome.

ISI Group analyst Mark Schoenebaum, who covers Biogen, cautioned that cross-trial comparisons are difficult to make, but also pointed to the lack of hypersensitivity in Biogen’s trial as a potential marketing advantage. He described the two products as “probably competitive” as they have similar half-lives.

With planned submissions to the FDA, European Medicines Agency and other regulators in the latter half of 2015, Bayer does not appear to be in a position to draw even with Biogen. It has instead dangled the prospect of a better drug in front of physicians and patients. Biogen is still odds-on to be the first mover, but Bayer should be a solid competitor.

To contact the writer of this story email Jonathan Gardner in London at [email protected] or follow @JonEPVantageon Twitter

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