A new wave of hemophilia treatments
20,000 in the U.S.
% with inhibitors:
~30% for hemophilia A
About 10 companies control the bulk of the hemophilia market, but gene therapies from smaller biotechs could upend the standings.
Transparency Market Research predicts the global hemophilia drug market will suprass $25 billion by 2024, up from $15.8 billion in 2015.
The hemophilia drug space had been pretty uneventful until a few years back. Sure, the Food and Drug Administration would issue a new approval every now and then, but patients were still stuck with a market full of treatments that had to be taken daily in order to manage the rare bleeding disorder.
That landscape is shifting rapidly, however. The recent rise of longer-acting hemophilia medicines is allowing patients to go sometimes up to a week before needing another dose. And gene therapy developers are quickly moving in as well, offering potentially curative treatments that could — at the very least — be taken on a multi-year basis. While gene therapy may be still some ways off, new hemophilia products are already beginning to disrupt the market.
Many longer-acting hemophilia treatments, such as recombinant antihemophilic Factor drugs Eloctate and Kovaltry, have already supplied impressive returns. Bayer AG reported €1.17 billion worth of Kovaltry sales in 2016, while Bioverativ Inc.'s Eloctate snagged $186 million in the third quarter of 2017 alone. Yet, what made those drugs innovative not that long ago is now becoming more commonplace.
Since 2013, the FDA has approved about 10 new medications for hemophilia, many of which are taken a few times per week rather than each day. To stay competitive, drugmakers are investing heavily in products that either dose even less frequently or benefit patients who have inhibitors, a kind of antibody that attacks infused Factor proteins.
One of the most closely watched drugs in those regards is Roche AG's recently approved, once-weekly treatment Hemlibra (emicizumab). A bispecific antibody, Hemlibra binds to Factor IXa and Factor X, mirroring the role Factor VIII plays in the blood.
In the clinic, Roche first assessed its drug as a treatment for the roughly 30% of hemophilia A patients who have inhibitors to standard Factor VIII replacement therapies. Results from the late-stage HAVEN 1 and HAVEN 2 pivotal studies showed adults treated with Hemlibra had their bleeding rates reduced 87%, while children younger than 12 demonstrated "clinically meaningful" reductions in their number of bleeds over time.
And in November, Roche announced Hemlibra hit the primary endpoint of a third trial, HAVEN 3, that evaluated hemophilia A patients without inhibitors — an outcome that makes it applicable to a much larger section of the hemophilia population.
In spite of the robust efficacy data, Hemlibra faces some challenges. Roche confirmed last November that four serious adverse events had occurred in the HAVEN 1 trial, including two instances of a type of blood clot called thrombotic microangiopathy. Concerns about the drug's safety were reignited several months later when another patient in HAVEN 1 died, though the trial investigator determined the death was not related to Hemlibra.
What's more, Shire has filed an injunction against Roche claiming the Swiss drugmaker spread an "inaccurate and misleading characterization of the serious adverse events that occurred in the HAVEN 1," as well as "disparaged" the safety of Shire’s own bypassing agent Feiba.
Challenges aside, the Food and Drug Administration accepted the New Drug Application for Hemlibra under priority review in August, and approved it several months ahead of its Feb. 23 target action date.
Gene therapy's momentum
While much further off, gene therapies also threaten to disrupt the hemophilia market. For example, a Phase 1/2 open-label study testing BioMarin's BMN270 in hemophilia A patients with severely low amounts of clotting Factor VIII found that, after one year, everyone who took the drug was maintaining mean and median Factor VIII levels above 50%, putting them in the healthy range. BioMarin has plans to initiate a registrational study of BMN270 by year's end. If all goes well, the company may have a gene therapy for hemophilia on the market as early as 2019.
Spark Therapeutics Inc. and Pfizer Inc. also touted positive Phase 1/2 data for their hemophilia B gene therapy SPK-9001 this past summer. Alnylam Pharmaceuticals Inc. and Sanofi SA, meanwhile, are trying to show their RNA interference drug fitusiran is a sort of all-purpose asset. It's under investigation as a treatment for hemophilia A and B with or without inhibitors, though Alnylam had to recently suspend dosing in all fitusiran studies after a fatal thrombotic event occurred in a Phase 2 open-label extension study.
While these treatments are injecting much-needed innovation into hemophilia drug development, they're also threatening to upend legacy brands. Danish pharma Novo Nordisk A/S, for instance, anticipates that 50% of sales of NovoSeven, its drug for hemophilia A patients with inhibitors, could eventually be exposed to competition from Hemlibra. And Shire expects newcomer therapies — including but not limited to Hemlibra — to erode about half of its Feiba franchise by 2022. Sales of NovoSeven and Feiba hit about $1.36 billion and $800 million, respectively, in 2016.
Companies expect a hit to their revenue if competing hemophilia treatments are approved
- Top hemophilia drugNovoSeven
- 2016 product sales$1.5 billion
- Revenue at risk50% of NovoSeven sales in hemophilia A patients with inhibitors
- Top hemophilia drugFeiba
- 2016 product salesApprox. $800 million
- Revenue at risk50% of FEIBA sales in hemophilia patients with inhibitors by 2022
"[O]ur analysis would argue that investors are now viewing the competitive threats as though they are nearly catastrophic," Cowen & Co. analyst Ken Cacciatore wrote in an Oct. 27 note after Shire reported its third quarter earnings. "Indeed, it is our view that at the current price, it would appear that investors are treating Shire/Baxalta's hemophilia franchise as if it should equate to essentially zero, into perpetuity, beginning in 2020."
For whichever companies or products rise to top in the shaken-up hemophilia space, there is potential for big profits. While the disorder only affects around 20,000 people in the U.S., analysts expect spending on rare disease treatments will increase in the coming years. And market researchers expect the global hemophilia drug market to reach $15 billion to $25 billion by 2024.
Approval of Roche's Hemlibra kicks off what looks set to be a wave of longer-acting treatments entering — and disrupting — the hemophilia market.