Event – Biogen's long-acting haemophilia agents near clinical validation

While much of the excitement surrounding Biogen Idec stems from the expected approval and launch of its MS pill BG-12, the Massachusetts group may have another string to its bow: its phase III haemophilia candidates. Pivotal results are expected by the end of the year for both factor VIII and factor IX agents.

The drugs, which are partnered with Swedish Orphan Biovitrum in Europe, hold the promise of extending dosing intervals from every other day to as infrequently as once weekly. With haemophilia specialists and patients seeking to prevent spontaneous bleeds, a longer dosing interval would give the products a clear commercial advantage.

Company Biogen Idec Swedish Orphan Biovitrium
Product rFVIIIFc rFIXFc rFVIIIFc  rFIXFc
Market cap $34bn $902m
Product NPV $267m $133m $195m $78m
% of market cap 1% 0% 22% 9%
Event type Phase III results
Date H2 2012

Dosing advantage

rFVIIIFc and rFIXFc are coagulation factors VIII and IX fused with a protein designed to extend their half-lives; the former aims to treat the more common haemophilia A and the latter haemophilia B.

Haemophilia therapy has evolved from episodic treatment to a preventative approach as specialists try to avert the internal bleeding that can lead to disabling joint destruction or arthritis, one of the major complications of the genetic disorder.

Current therapies such as Baxter’s Advate and Bayer’s Kogenate are typically infused intravenously two to three times a week in a prophylactic setting (Therapeutic focus - Long-acting haemophilia agents set to shake things up, July 26, 2011). For example, the label of Advate, the biggest-selling factor VIII in 2011 with $1.91bn, recommends dosing once every other day but allows for dosing every third day to keep blood levels at least 1% of normal.

As such, extending the half-life of the clotting factor could reduce the number of doses necessary to prevent bleeding episodes. Specialists and patients would view this as a step forward, as the cumbersome dosing profile is is thought to discourage around half of all severe haemophilia A and B patients from pursuing regular, preventative infusions.

One phase III trial from each factor is expected to report data by the end of 2012. The A-Long trial is testing rFVIIIFc in on-demand treatment against weekly infusions and also contains an arm that started patients at twice a week but then tailored dosing to maintain a factor VIII trough of between 1% and 3% of normal levels. The trial is designed to end when patients in the tailored dosing arm reach 50 exposures.

The B-Long study follows similar dosing regimens with the factor IX. In both trials, investigators will be looking for a significant decrease in the number of bleeding episodes.

Biogen executives have cast doubt on whether once-weekly dosing of the factor VIII will prove effective. However, side-by-side comparisons of the trial arm with the tailored dosing group will give some indication of what an optimal dosing schedule could look like.

Building a franchise

For Biogen the development of a haemophilia franchise will be an important contributor to company’s revenue. Haemophilia does not represent the most important product in the clinic; according to analysts' sales forecasts this honour belongs to the pegylated version of Biogen's MS treatment Avonex, which is also in phase III.

Of its clinical stage products, the factor VIII is forecast to achieve sales of $144m and factor IX $76m in 2018 – although expectations remain modest for both and some analysts have not forecast sales for either. With phase III success these numbers are likely to increase as hopes for approval and launch rise.

For Swedish Orphan Biovitrum, which licensed Europe, Russia and Middle East rights from Syntonix before Biogen bought the private biotech in 2007, the two proteins are much more important. They constitute the group’s two biggest growth drivers, and the factor VIII is forecast to be the biggest selling product in 2018.

However, because the European Union wants paediatric trials completed before filing, Swedish will not be able to launch at the same time as Biogen if the adult trials are successful. The Kids A-Long and Kids B-Long trials are not expected to report data until 2014 and 2015 respectively.

Given the desire to reduce the burden of disease, both in terms of disability and dosing, patients and specialists are no doubt hoping for a treatment that can help with both. Demonstrating efficacy and safety at a weekly dosing schedule would be a straightforward win for the Biogen-Swedish factor VIII and IX; however, even a twice-a-week infusion would have its advantages. The evolution of haemophilia therapy will become more clear once these phase III data have been disclosed.

Trial IDs A-Long NCT01181128
B-Long NCT01027364

To contact the writer of this story email Jonathan Gardner in London at jonathang@epvantage.com

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