FEATURE
Drawing First Blood
was administered in much higher doses than we
would typically use in clinical practice. So, if you
are going to use it blind – without measuring
FVIII activity – then I think you have to use it
on-label. In this case, that means overshooting
with FVIII and potentially increasing thrombotic risk.
Dr. Kruse-Jarres: That’s absolutely true. rpFVIII is
a drug that not only can, but must, be monitored.
Because people have very different rec overies and
half-lives in response to it, it is difficult to predict
how patients will respond.
The total cost of her rpFVIII during that
admission was $6 million. Medicare declined the
bill three times. That is a huge financial hit for
any medical center. Last year, we treated four patients with rpFVIII and our hospital was charged
$12 million. Fortunately, the drug was efficacious
and patients are doing well; however, the cost issues are a phenomenal barrier. It sometimes puts
me in the position of using my second choice of
drug to treat patients until they experience harm
before I can use my first choice.
“[There may never]
need rpFVIII infusions every three or four hours,
be a clinical trial
while some need an infusion every eight to 12
hours. Also, the same patient can go from needthat will definitively
ing rpFVIII every three to four hours to every
eight to 12 hours with prolonged exposure.
prove whether
Or vice versa. We also have
rpFVIII or bypassing
to consider that, because people treated with
rpFVIII can develop inhibitors to porcine FVIII
over time, the response to rpFVIII can lessen over agents are the best
time. This makes monitoring so important.
I would add that patients with relatively mild
choice for AHA
bleeding probably benefit from being treated with
a bypassing agent [rather] than rpFVIII. These
patients, because
patients should be started on a bypassing agent so
they aren’t exposed to the porcine FVIII; treating
there are not
a minor bleed with rpFVIII first could trigger the
development of antibodies to the porcine FVIII,
enough patients to
so we would want to preserve rpFVIII in case the
patient has a more severe bleed later.
be able to accrue to
So, we agree that there are definite situsuch a clinical trial.”
ations where bypassing agents would be our
Dr. Ma: Secondly, patients vary greatly – some
Dr. Kruse-Jarres:
Dr. Ma:
preferred first-line therapy. Despite this, I also
want to make it clear that I like rpFVIII. I think
it is a wonderful drug. Patients respond to it, and
I can determine their hemostatic levels based on
their FVIII activity. It gives me a level of confidence that I’m achieving a satisfactory FVIII level
for my patients.
That being said, it costs $4.56 a unit. A costcomparison between patients treated with the
standard bypassing agents demonstrated that
rpFVIII comes out at least twice as expensive as
these agents. If the costs were lower, we would
consider it first-line therapy for our patients, but
because of the pricing strategy, I am forced to use
a more physiologic agent that might not be the
one I’d like to use.
Dr. Kruse-Jarres: Perhaps, but if you have a patient
who may only need rpFVIII at 50 μ/kg every 12
hours, it will be cheaper than the bypassing agents
– even at the current price. However, if you have
to use 200 μ/kg every four hours, then it definitely
becomes much more expensive.
Dr. Ma: I can give you one costly example: Our
first experience with rpFVIII was treating an
older woman who had not responded to rFVIIa.
Our pharmacist eventually allowed us to use
rpFVIII, which turned out to be very effective.
However, the patient went on to have more bleeding episodes during that same hospital admission
– as patients with AHA are prone to do – and she
was in the hospital for about six weeks.
44
ASH Clinical News
—REBECCA KRUSE-JARRES, MD, MPH
Dr. Kruse-Jarres: Related to the cost issue is the
ease-of-access issue. At our center, we are having
major issues with getting the drug on time.
rpFVIII is supposed to be delivered to the hospital within six hours, but that has not been the
case. With the last patient who needed it, it took
more than 24 hours to receive it. In addition,
the pharmacist has to execute a contract with
the distributor to get the drug; when a patient
presents on a Friday night, for instance, getting
that contract can be difficult.
Dr. Ma: At our institution we may stock an ex-
pensive and uncommonly used drug by buying
it on consignment. The pharmaceutical company puts the drug on the hospital’s shelf, but the
hospital isn’t charged until the drug is used. In
this situation, the price the hospital pays at the
time the drug is used is higher than the price for
buying it outright, but hospitals pay that higher
price for the convenience.
Dr. Kruse-Jarres: We have not yet figured out
how to purchase the drug on consignment in
our pharmacy. I might not see any patients with
AHA for the next year. At that point, the product
I bought would already be outdated, and I would
have lost $100,000 or $300,000 in product that I
am responsible for.
In the clinical trials for rpFVIII, we used
it completely differently than how we would
use it in real-world practice because we were
not hindered by the price. I can recall one trial
participant who was receiving massive amounts
of rpFVIII – 300 to 400 μ/kg every two to three
hours for a month. Eventually, after a month, her
inhibitor activity went so high that I couldn’t treat
her with rpFVIII anymore. That simply could not
happen in clinical practice.
Dr. Ma: Not if you wanted to stay employed!
At our hospital, we have treated six patients.
It would have been cost-effective to use rpFVIII
in three of these patients because the genetics of
their antibodies were such that we did not have
to use very much of the drug. In other patients,
though, rpFVIII has been overwhelmingly more
expensive than a bypassing agent would have
been. Again, we only used rpFVIII because
bypassing agents were either ineffective or too
pro-thrombotic.
Rebate programs might help with this
problem, but overwhelmingly, the answer from
our pharmacy and physicians at our hemophilia
treatment center has been that the drug is too
expensive and prohibitive. All patients are different; some patients will end up being more
cheaply treated with rpFVIII and some will
be more expensive. But, because of the cost of
rpFVIII, I cannot have it on my formulary. This
is a regulation that has been externally imposed
on me solely because of the cost.
Before rpFVIII was approved, we had rFVIIa
and FEIBA. They weren’t perf ect, but they
worked pretty well. When rpFVIII was approved,
everyone was excited to have another option, but
then we saw the price. As a physician, it’s very
frustrating to not be able to use what I would like
to use, and what I know would be effective for
my patients. If price was not an object, I would
be inclined to use rpFVIII upfront and switch
to a bypassing agent if the patient developed
neutralizing antibodies to rpFVIII.
Dr. Kruse-Jarres: Unfortunately, I don’t think
there will be a clinical trial that will definitively
prove whether rpFVIII or bypassing agents are
the best choice for AHA patients, because there
are not enough patients to be able to accrue to
such a clinical trial. When we’re thinking about
which agent would be the optimal choice for
most AHA patients, we have to ask, ‘If we have
adequate alternatives, like the bypassing agents,
why would we prescribe the more expensive
option?’ In my opinion, the answer is simple:
rpFVIII fixes the hemostatic defect, and it is the
most targeted therapy. ●
Editor’s note: Since this interview was conducted,
the manufacturer of rpFVIII (Obizur; Baxalta)
has lowered the price per unit to $3.40. However,
Dr. Ma noted that the UNC pharmacy is “still not
willing to place it on its formulary.”
October 2016