* Shift to longer-acting factor replacement therapies
* Roche's Hemlibra expected to take significant market share
* Gene therapy raises prospect of cure to bleeding disorder
LONDON, Jan 22 (Reuters) - Sanofi is placing a big bet on the $10 billion-a-year hemophilia market at a testing time, as scientific advances overhaul traditional approaches to treating the rare uncontrolled bleeding disorder.
The French drugmaker's decision to buy U.S. hemophilia specialist Bioverativ for $11.6 billion exposes it to competition from Roche's new drug Hemlibra and looming threats from gene therapy. It also offers a potential launchpad for Sanofi's own experimental medicine fitusiran.
Patients with the genetic blood disorder have traditionally depended on receiving factor replacement therapies, sometimes as often as every other day.
Today that standard approach to therapy is changing with the development of long-acting treatments - of which Bioverativ's Eloctate and Alprolix are successful examples - and other non-factor approaches.
Roche's recently approved Hemlibra will shake up the market by providing a once-weekly antibody injection for patients with hemophilia A who have developed inhibitors, or resistance, to other treatments.
And several drug companies hope to take things to a whole new level with gene therapy, in which a harmless virus is used to introduce DNA to fix the faulty genes behind the disease, offering a possible one-off cure.
Excitement about the potential of gene therapy has been spurred by recent promising clinical trial data from the likes of Biomarin and Spark Therapeutics, prompting the New England Journal of Medicine to declare in an editorial last month that a cure was "within reach."
The recasting of the hemophilia landscape poses a threat to players reliant on factor replacement therapies, notably market leader Shire, which has been out of favor since buying hemophilia specialist Baxalta two years ago.
Also being challenged by new hemophilia medicines are Bayer , CSL and Novo Nordisk, the last of which has responded by trying to buy Ablynx to shore up its own blood disease business.
Bioverativ's factor-dependent business is also at risk, although its longer-acting products, which are sold in Europe by Swedish Orphan Biovitrum, give it a relative advantage.
Sanofi Chief Executive Olivier Brandicourt argues that factor replacement therapy will remain the standard of care for many years, given its established safety profile and the advances Bioverativ has made with long-acting products.
He is also banking on Bioverativ to leverage commercialisation of fitusiran, a new kind of so-called RNA interference treatment for hemophilia A and B that Sanofi is developing with Alnylam Pharmaceuticals.
However, despite a solid strategic rationale and a predicted boost to earnings, Deutsche Bank analysts said Brandicourt's decision to invest in an "out-of-favor therapy area" would detract from investor enthusiasm.
Sanofi shares fell more than 3 percent on Monday after the company announced its acquisition of Bioverativ, while Kepler Chevreux said the parallel with Shire's unpopular acquisition of Baxalta raised "a host of questions." (Reporting by Ben Hirschler; Editing by Susan Fenton)