CLINICAL
NEWS
TABLE
American College of Cardiology Extended Learning
Base Case* and Clinical Outcomes among Patients with FH
Person-years of
treatment
(millions)
Total MACE
averted
NNT
for 5 years to
avert one MACE
22.3
23.7
115,900
324,200
77
28
Statin
Statin + Ezetimibe
Statin + PCSK9 inhibitor
QALYs gained
Comparator
250,600
665,200
Incremental
Drug Costs
(million $)
Incremental
Costs, Other
CV Care
(million $)
ICER
($/QALY)
$40,359
$210,516
-$6,632
-$17,304
$135,000
$290,000
CV = cardiovascular; FH = familial hypercholesterolemia; ICER = incremental cost-effectiveness ratio; MACE = major adverse cardiovascular event (nonfatal MI, nonfatal stroke, and CV death);
QALY = quality-adjusted life year.
• Why are underpowered data sufficient to make
treatment decisions on subpopulations (women
and non-whites)?
• Is it time to stop comparing women to men and
fund an adequately powered primary prevention
women-only trial?
FAMILIAL HYPERGLYCEMIA
Over the past decade, John J.P. Kastelein, MD,
PhD, of the Academic Medical Center/University
of Amsterdam, notes that we have witnessed
the unparalleled success of statins to treat dyslipidemia. Target identification by Mendelian
randomization, human monoclonal antibodies,
gene therapy, RNA-based targets, and atherogenic
lipoproteins other than LDL-C have fueled intense
development efforts that may bear fruit, providing
new treatment options, in the very near future.2
However, right now—as noted earlier in this
issue of ACCEL—there are two new PCSK9 inhibitors, which, Dr. Kastelein said, has converted familial
hypercholesterolemia (FH) from a lethal disorder to
a manageable dyslipidemia. Given strong evidence
that lower LDL-C is better in
these individuals, now one of
To listen to the
the challenges is finding them,
interview with C.
preferably before their first
Noel Bairey Merz,
myocardial infarction brings
MD, visit the CSWN
YouTube channel
them to medical attention.
or scan the QR.
Just how many patients
Interview conducted
by Michael Hugh
will likely be put on these
Sketch, Jr., MD.
new monoclonal antibodies
to PCSK9? Assuming that
the early use will be limited
to FH patients and for very
high-risk patients with documented statin intolerance, Dr.
Bairey Merz estimates that, for
the foreseeable future, use of
PCSK9 inhibitors will be limited to roughly 10% or
less of the CVD population.
OUCH – AND NO THANK YOU
That may seem like a small percentage of patients
given that these drugs are more powerful than
statins. Cost is definitely a consideration, given that
PCSK9 pricing levels are now known, running a
22
CardioSource WorldNews
little over $14,000 per year in the U.S. That’s well
above earlier analyst estimates and on another
planet from a Sept. 2015 draft report from the
U.S. Institute for Clinical Economic Review (ICER),
suggesting that the drugs should cost approximately 85% less than priced. (Which would reduce
the price to about $175 a month.) In case you’re
wondering, the annual cost of ezetimibe is $2,828,
based on wholesale acquisition cost.
Wow, what do you think the final report will
say? Let’s look, because it was published Nov. 24,
2015.3 After various analyses, including cost effectiveness and number needed to treat, the draft
ICER value-based price benchmark for each of
the new PCSK9 inhibitor drugs was $2,177. As
the report states, “This figure represents an 85%
discount from the full wholesale acquisition cost
assumed in our analysis ($14,350).”
The ICER study authors did use a budget impact
model to estimate what would happen if both the FH
and cardiovascular disease (CVD) populations were
treated based on certain uptake pattern assumptions. They estimate that 527,000 individuals will
receive PCSK9 therapy in the first year. After 1 year
of PCSK9 treatment, cost offsets due to reduced
cardiovascular adverse events were estimated to
range from $592 per patient with FH to $1,010 per
patient for patients with CVD who are statin-intolerant. Including th is cost offset, their estimated 1-year
budget impact is still high: approximately $7.2 billion for all patient populations.
The TABLE demonstrates that, compared with
statin therapy, incremental treatment with ezetimibe
would avert 115,900 Major Adverse Cardiac Events
(MACE) over the lifetime horizon and produce
250,600 additional QALYs with an incremental
cost-effectiveness ratio of $135,000/QALY vs. current (statin) treatment. Adding PCSK9 inhibitors to
current treatment would avert 324,200 MACE and
produce 665,200 additional QALYs, producing an incremental cost-effectiveness ratio of $290,000/QALY.
This higher ICER for PCSK9 inhibitors is driven
largely by differences in the drug costs noted above.
Here are a few more numbers: As uptake of new
PCSK9 inhibitors is estimated to increase over the
first 5 years of use, the ICER report estimates that
approximately 2.6 million persons will receive PCSK9
inhibitor therapy for 1 or more years by the end of
that period. Total budgetary impact over 5 years is
estimated at approximately $19 billion, $15 billion,
and $74 billion for the FH, CVD statin-intolerant, and
CVD not at LDL-C target subpopulations, respectively.
Finally, what’s happening in the real world as
decisions are made about these newly approved
agents? On Nov. 24, 2015, CVS announced that only
evolocumab will be offered in the U.S. in the CVS/
Caremark commercial formularies. In a press release,
the company said the decision came after a thorough
evaluation of the two new PCSK9 inhibitor therapies.
“We have determined that choosing a single PCSK9
inhibitor for our commercial formularies allows us
to get the best price possible,” according to Troyen
A. Brennan, MD, MPH, executive vice president and
chief medical officer, CVS Health.
That’s the opposite of what happened a few days
earlier when the UK’s National Institute for Health
and Care Excellence (NICE) published draft guidance not recommending evolocumab as an option
for people with primary hypercholesterolemia—
heterozygous-familial and non-familial—and mixed
dyslipidemia. The UK price was too much for the
regulators to stomach: annually, it is the British
pound equivalent of $6,763.49 for 140 mg every 2
weeks and $9,310.10 for 420 mg/month.
It is doubtful we have heard the last of the
PCSK9 cost debate. ■
REFERENCES:
1. Stone NJ, Robinson JG, Lichtenstein AH, et al. J Am Coll
Cardiol. 2014;63:2889-934.
2. Kastelein JJ. Nat Rev Cardiol. 2014;11:629-31.
3. Tice JA, Ollendorf DA, Cunningham C, et al. for the Institute for Clinical and Economic Review. PCSK9 Inhibitors
for Treatment of High Cholesterol: Effectiveness, Value,
and Value-Based Price Benchmarks. 2015 Nov. 24: 1-113.
Available online: cepac.icer-review.org/adaptations/cholesterol/.
Take-aways
• Despite recent (and recently validated) guidelines
on cholesterol management, major issues remain.
• One issue is the large “doughnut hole” of missing
data on key subgroups, such as women and nonwhite individuals.
• A second issue is how broadly the new PCSK9
inhibitors will be used given their costs.
January 2016