Three forces will drive costs for hemophilia treatment going forward. The first is the rapid rise in life expectancy for hemophiliacs as improved treatment regimens successfully confront the disease. The second is the continued role that inhibitors play. The third will be the appearance of new drugs which are already proving to be more expensive.
Driver 1: Longer lifespans
This long-term cost driver is just beginning to come in for closer scrutiny. The appearance of safe, reliable factor replacement therapies have helped to stabilize hemophilia patients and give them much more normal lives. As a result, we face a demographic shift with increasing numbers of persons afflicted with the disease are now living far longer than they once did, even just a few decades ago.1
In the 1800’s, patient life expectancy was only about 13 years.2 By the 1960’s it had improved somewhat, to about age 20.2 Today, a baby born with hemophilia in one of the advanced economies can expect to live a normal lifespan (with proper treatment).1, 3
This sudden advance in longevity has both obvious and non-obvious implications.
At the obvious level, while the cost to treat hemophilia shows no signs of coming down, we shall need to treat these patients for many years. And, drug makers are increasingly turning their attention to newer drugs that will seek to improve patient quality of life with simpler, longer-lasting treatments. We can expect these newer drugs to be more expensive.
At the non-obvious level, as patients’ lives become more normal, they increasingly have opportunities to develop problems that previous generations of hemophiliacs did not. For example, until recently little was known about low-bone density problems (osteopenia) among hemophilia patients.1 No one had the time to study it. Other problems are similarly gaining new-found attention, like obesity and aging issues.
Take obesity. Now that hemophilia patients are living long enough to become obese, about 50 percent of them have done so.1 This is important, because factor concentrate dosing (and cost) is based on body weight. However, while all heavier patients receive higher doses of factor, it is not clear that obese patients actually need it, because fatty tissue has less blood supply than lean tissue.1
More research is needed in order to fully understand the implications of these changing demographics. However, it seems clear that, as a result of these and other challenges, the cost of care for hemophilia will continue to rise.
Driver 2: Inhibitors
Some patients develop a resistance to clotting factor infusions. Essentially, the body develops an allergic reaction to the clotting factors. The immune system begins to consider the factor as a foreign substance and tries to destroy it using inhibitor antibodies.4
About one-third (30 percent) of patients with severe Type A and up to 5 percent of those with Type B develop a resistance after receiving clotting factor infusions over a period of time. 4 About 1,200 Americans with hemophilia have inhibitors.5
When people develop inhibitors it becomes extremely difficult to control their bleeding episodes. These patients must receive additional therapy to help them overcome that resistance. These are some of the most expensive cases to treat.6
One treatment for inhibitors involves infusing the patient with special “bypass agents.”6 Bypass agents avoid the immune system response by using a different chemical pathway to support clotting that “bypass” the mechanism controlled by the clotting factor concentrate.6
Bypass agents can be effective to control bleeding, but they can also be difficult to use and have side-effects of their own.6 Other treatments require patients to receive very large amounts of clotting factor concentrates every day for many weeks or months in an effort to “teach” the body to accept clotting factor concentrate treatments.7
All of these treatment options – plus additional ER visits and hospitalizations due to increased bleeding – can push overall treatment costs up very high for inhibitor patients. The cost for bypass agents alone averages around $300,000 per year.8 CDC researchers found that the average yearly health care bill for patients with inhibitors was nearly five times higher than for patients without inhibitors (see graphic).
Driver 3: New drugs
The market for hemophilia drugs is seeing an influx of new drugs.9 Some, with slightly longer periods needed between treatments, have already arrived. Other, even longer-lasting clotting factors are also on their way.
Two new Biogen products (Aprolix® for type B & Eloctate® for type A) are longer-acting than traditional treatments. They require only one to two infusions per week, as opposed to the commonly used regimen of three infusions per week.9 Even this relatively small change in frequency translates into 50 to 100 or fewer infusions per year and a correspondingly smaller number of units infused per patient.
When the new concentrates were announced there was speculation that the combination of longer treatment intervals and similar overall cost would mean that existing patients would quickly move toward the new Biogen products.10 This has not occurred.11
One big reason is that the new concentrates may not actually represent a significant clinical advantage; rather, they may simply be more convenient to use. Based on a clinical review of available evidence, UnitedHealthcare has determined that Eloctate may not be medically necessary in all cases. While it is covered under our fully-insured contracts, patients must first demonstrate that the existing alternatives are not sufficient. (ASO and carve-out clients make their own coverage determinations. Contact your consultant, broker or representative for details.)
Another reason for the slow uptake appears to be the highly individual nature of hemophilia and its treatment. Patients who respond well to one treatment may not fare well with another. Consequently, hemophilia patients who are stable in their treatments are reluctant to change treatments and their doctors are equally reluctant to recommend a change.11 One indication that this is happening is that, during the last quarter of 2014, when Eloctate was available on the market, its sales hardly moved, while an older product from Bayer (Advate®) actually saw increased sales (+ seven percent).11
One thing we know for sure is that there will be no shortage of new products coming on the market. The Canadian Hemophilia Society (CHS) recently counted no fewer than 29 new therapies in development, including 11 for type A, eight for type B, eight new bypassing therapies, plus two others.12
The CHS has broken these new drugs into three categories:
- Greater clotting potency
- Extended factor half-life
Greater clotting potency: This can be especially important for patients with inhibitors.15 Unlike drugs that simply add convenience, a clotting factor with dramatically improved clotting potency would probably be covered by insurance. That’s a necessary improvement – maybe even at a premium price.
Extended factor half-life: These improvements seek to increase the time the clotting factors remain effective in the patient’s bloodstream after being infused. Current treatments can fall by half in the body in a matter of hours after infusion. New versions hope to extend the time between infusions from every two or three days to once every 10 days or two weeks, or even longer.12 (See chart, below.)
But we’ve already seen how just extending the time between infusions from two or three days to four or five is seen as mainly more convenient; and so may not be covered. But what happens if the time between infusions gets extended to two weeks? Presumably there is some threshold where a long enough interval attains a clinical or cost significance and begins to warrant coverage. It is at this point that higher drug prices will begin to have their impact.
Portfolio-builders:These are frankly aimed at permitting manufacturers to participate in more phases of the hemophilia market. So where today a manufacturer might sell only a type B clotting factor, by adding new drugs they can compete in type A and in bypassing agents as well.12
While portfolio-building might appear to be solely in the manufacturer’s own self-interest, it may well turn out that having more manufacturers competing in the space will be a good thing for everyone. For example, we might see a new clotting factor that has a marginal performance improvement, but a dramatically lower price.
Overall we know costs will go up because a growing number of hemophilia patients will outlive their predecessors and live on into their 60s and 70’s. They will require more and different care.
With over two dozen new products currently in trials, OptumRx will continue to monitor new developments from the standpoint of finding the best clinical performance and the best overall economic value for our customers. We expect that this large number of new products will lead to more competition within the class and possibly greater price sensitivity.