Haemophilia A therapy has needed fresh blood for some time – it is dominated by old drugs that must be taken every couple of days, meaning that patients usually only use them when they have a potentially dangerous bleed.
All this looks set to change with the arrival of the first long-acting factor VIII agents, which promise less frequent dosing and make prophylactic use more realistic (see table below). These should protect patients from the side-effects of bleeding – as well as the immediate risk of death these include joint damage – in addition to being a boon to the pharma industry. More regular use should equal big sales for whoever comes out on top of this sector.
Biogen’s Eloctate was the first of these long-acting agents to hit the market with US approval in June 2014 (Eloctate approval confirms Biogen Idec growth story, June 09, 2014). This was followed by the green light in Europe this week for both on-demand and prophylactic use – here, the drug will be called Elocta and be marketed by Swedish Orphan Biovitrum (Sobi).
Eloctate is given via IV infusion every three to five days, compared with every other day for the current market leader, Baxalta’s Advate. Older drugs must be administered this frequently because of their short half-lives, and companies have taken various approaches to extend these for the longer-lasting versions.
In spite of the inconvenient dosing schedule with older drugs, 80-90% of children and 40-60% of adults in Europe are on prophylactic therapy, Jefferies analysts estimate – so Biogen and Sobi have a good chance of converting this population.
But they are already facing competition in the US, where Baxalta’s Adynovate, which has a similar schedule of twice-weekly dosing, got FDA approval earlier this month. While Eloctate is a fusion protein, Baxalta has gone for pegylation to extend Adynovate’s half-life.
And two more drugs could soon join them: Bayer’s 81-8973, now known as Kovaltry, and CSL Behring’s single-chain recombinant factor VIII. The former should be first, with a PDUFA date of December 17 and a decision in Europe expected by January 2016.
|Selected long-acting factor VIIIs|
|Eloctate||Biogen/Sobi||Fc fusion protein||Approved in EU and US||Every 3-5 days|
|Adynovate||Baxalta||Pegylated||Approved in US||Twice weekly|
|BAY 81-8973/ Kovaltry||Bayer||Kogenate follow on; slightly longer acting||Filed||2-3 times weekly|
|Recombinant factor VIII||CSL Behring||Single chain factor VIII||Filed||2-3 times weekly|
|BAY 94-9027||Bayer||Pegylated||Phase III||Studied once weekly|
|N8-GP||Novo Nordisk||Glycopegylated||Phase III||Studied every 4 days|
|BAY 79-4980||Bayer||Pegylated||Phase II||Studied once weekly|
Biogen and Sobi will be banking on their headstart paying off. The Jefferies analysts believe that, once haematologists are using a long-acting product, switching to another will be unlikely, based on their survey of the specialists.
But there is a threat of products with even higher convenience coming onto the market. The first once-weekly factor VIII is likely to be BAY 94-9027, which Bayer is expected to file in the US and EU by the end of the year. A pivotal trial tested dosing every two, five or seven days (Bayer closes the gap on Biogen’s haemophilia candidate, February 18, 2014).
Indeed, Bayer is the most active player in the long-acting factor VIII space, with three candidates in phase II or III development; the other is BAY 79-4980, another potentially once-weekly agent.
Novo Nordisk, meanwhile – which already markets the NovoSeven factor VII rescue agent – is developing N8-GP, which was given every four days in the phase III pathfinder2 study.
But, in spite of the promise of long-acting drugs, conventional agents are looking hard to shift. Advate is still set to be the number-one haemophilia A drug in 2020 and Eloctate will be the only long-acting factor VIII to make it into the top five, according to EvaluatePharma consensus forecasts.
Is this a symptom of the conservative haemophilia market, or just that many have underestimated potential sales for the longer-acting agents? Either way, Biogen and Sobi need to make the most of their first-mover advantage before Eloctate is superseded by the incoming once-weekly products.
|Top five haemophilia A drugs in 2020|
|Drug||Company||Class||First launched||2014 sales ($m)||2020e sales ($m)|
|NovoSeven||Novo Nordisk||Factor VII||1996||1,629||1,679|
|Eloctate||Biogen/Sobi||Long-acting factor VIII||2014||58||1,321|
|FEIBA VH||Baxalta||Anti-inhibitor coagulation complex||1979||740||961|