A Cost Efficiency Model for
Comparing On-demand Treatment
Costs in Hereditary Angioedema
Frank J Rodino, MHS, PA1; Sandra Westra, PharmD1
1Churchill
Outcomes Research, Maplewood, New Jersey, USA
OBJECTIVES: To present simple, objective, and customizable cost estimation formulas to compare
per-attack treatment costs of four recently FDA-approved hereditary angioedema (HAE) products.
METHODS: Products developed for small orphan disease populations such as HAE are predictably
costly. Comparing treatment costs among new HAE therapies is complicated by differences
in dosing recommendations and re-dosing probabilities. We propose a simple cost estimation
formula that factors in the non-static variables of body weight and re-dosing likelihood per
attack based on official prescribing recommendations and published clinical study data. Other
administrative or indirect costs were not factored into the formulas.
RESULTS: Formulas were developed that allow insertion of local acquisition costs for any of the
HAE products, according to the quantity of vials or syringes required for initial dosing. A weighted
percentage of the cost of the initial dose was added to determine the total cost, factoring in the
anticipated need for re-dosing. For products having more than one published re-dosing frequency,
the lowest reported frequency was used as a conservative approach. Specific cost estimation
formulas address three theoretical patient weight categories: < 40 kg (to reflect small adults or
pediatric patients), a standard 75 kg adult, and obese patients weighing between 100-125 kg.
CONCLUSIONS: While therapy choices in HAE should be primarily driven by clinical factors and
patient preferences, cost of treatment can be an important consideration if multiple options are
considered equally appropriate. The formulas presented provide a simple, objective means of
quickly comparing direct product costs for treating an HAE attack using local pricing figures.
Introduction
n Hereditary angioedema (HAE) is a rare, debilitating, and potentially life-threatening chronic
disease associated with frequent, unpredictable attacks of painful, non-pitting, non-pruritic
edema.1,2
n Since 2009, four highly effective agents have received FDA approval for the on-demand
treatment of acute attacks of HAE: pasteurized, nanofiltered, plasma-derived C1-INH
concentrate (pnfC1-INH/Berinert®), ecallantide (Kalbitor®), icatibant (Firazyr®); and
recombinant human C1-INH (rhC1-INH/Ruconest®) (Table 1). Another plasma-derived
C1-INH concentrate (Cinryze®) is approved for prophylaxis only and is not included.
n Drug treatments designed for orphan diseases such as HAE can be particularly expensive.3,4
While cost should only be one of many factors considered in choosing appropriate therapy,
the economic realities of today’s healthcare environment warrant such considerations,
particularly when multiple therapies are deemed clinically viable options.
n Comparing HAE treatments on a relevant basis of cost-per-treated-attack is complicated
because of differences in product dosing strategies (body weight-based versus fixed dosing)
and potential likelihood for re-dosing to control a given attack.
n We designed cost estimation formulas that factor in these different variables and provide a
quick and simple tool for roughly estimating comparative costs for the various HAE products;
the objective was to design formulas that incorporate the user’s own unique product
acquisition costs, realizing that purchasing plans and cost structures are often institutionspecific and manufacturer pricing changes over time.
Methods
n Simple cost estimation formulas that factor in the non-static variables of body weight and
re-dosing likelihood per attack were developed based on official prescribing
recommendations and published clinical study data; costs of injection/infusion equipment
were not included and would be expected to contribute little difference between the
products.
n The two major determinants of HAE treatment costs per product considered in the formulas
are 1) patient body weight and 2) re-dosing potential per attack.
1. Patient body weight - The cost estimation formulas were designed to encompass three
theoretical patient weight categories: < 40 kg (to reflect small adults or pediatric patients),
a standard 75 kg adult, and obese patients weighing between 100-125 kg.
• Dosing recommendations are body weight-based for pnfC1-INH.
• Dosing recommendations are fixed for icatibant and ecallantide
• Dosing recommendations for rhC1-INH are body weight-based for patients < 84 kg and
fixed dose for patients < 84 kg (Table 1).
2. Re-dosing potential - The formulas were weighted according to the potential need for
re-dosing for a given attack, based upon re-dosing/rescue treatment rates reported in
published clinical trials (Table 2).
• If more than one re-dosing rate appeared in published studies, the most favorable
reported rate for each product was used as a conservative approach.
Cost Estimation Formulas
n The first step in estimating cost per attack is determining the quantity of units (vials or
syringes) required to treat a single attack, per FDA product labeling.
– Icatibant and ecallantide are approved to be administered as a single 30 mg dose, while
pnfC1-INH and rhC1-INH are dosed based on patient weight (Table 3).
n The additional cost to account for potential re-dosing is determined by multiplying the
acquisition cost of the initial dose by a factor that conservatively reflects percentage of
attacks that may require re-dosing; this extra cost is added to the cost of the initial dose.
The formula is shown here in simplified form:
Attack treatment cost = AC + (AC X RD%)
Where AC = acquisition cost/dose; RD = re-dosing
n Table 3 provides specific formulas for each of the HAE products, including a breakdown by
body weight categories for those products that are dosed according to weight.
n The following hypothetical example illustrates use of the formula to estimate the treatment
cost of a product having an acquisition cost of $3000 per unit (eg, syringe or vial), 1 unit
required per dose, and a retreatment factor of 5%:
– Attack treatment cost = $3000 + ($3000 X .05) = $3150
n The user’s individualized acquisition costs for product vials and syringes are inserted into the
formulas in Table 3 (italicized text).
Conclusions
n Cost should never be the sole driver of treatment decisions, but is often a factor to be
considered among other clinical and situational determinants of management choices in
patients with HAE.
n In the current economic environment, it is important that clinicians and payers have an
appreciation for cost differentials if multiple treatment strategies are under consideration and
otherwise considered viable clinical options.
n One limitation of developing these formulas was sourcing re-dosing rates from studies with
design and terminology differences.
n The formulas presented here are simple and transparent for implementation using local
prices and allow for a rough comparison of on-demand treatment product costs for a single
HAE attack, factoring in the clinical reality of potential re-dosing, which adds to the cost of
treating an attack.
Table 1. On-demand treatment options for HAE
Trade name
Active ingredient
Manufacturer
Dosing recommendation
(Route of administration)a
Berinert5
pnfC1-INH concentrate
CSL Behring, Marburg, Germany
20 IU/kg bw (IV)
Firazyr6
Icatibant (bradykinin receptor
antagonist)
Shire, Lexington, MA, USA
30 mg fixed dose (SC)
Kalbitor7
Ecallantide (kallikrein inhibitor)
Dyax Corp, Burlington, MA, USA
30 mg fixed dose (SC)
rhC1-INH
Pharming Group NV, Leiden,
The Netherlands
<84 kg bw: 50 IU/kg (IV)
> 84 kg bw: 4200 IU (IV)
Ruconest8
bw=body weight; IU=international units; IV=intravenous; pnfC1-INH=pasteurized, nanofiltered C1-inhibitor concentrate;
rhC1-INH=human recombinant C1-INH; SC=subcutaneous
aDosing recommendations for an acute HAE attack according to product prescribing information
Table 2. Published clinical trials of on-demand treatment options for HAE in the US – study design
and efficacy outcomes
Product/Study
Na
Study design
Median time to onset of
relief, h (interquartile range)
Re-dosing
(% of attacks)b
pnfC1-INH
I.M.P.A.C.T.19
Randomized, double-blind, placebocontrolled, multicenter
43
0.5
NA
I.M.P.A.C.T.210
Open-label, single-arm, multicenter
57
0.46
1
FAST-111
Randomized, double-blind, placebocontrolled, multicenter
27
0.8 (0.5-2.0)
22
FAST-211
Randomized, double-blind (vs TXA),
multicenter
36
0.8 (0.4-1.4)
17
FAST-312
Randomized, double-blind, placebocontrolled, multicenter
43
1.5 (1.0, 2.0)c
9
EDEMA313
Randomized, double-blind, placebocontrolled
36
1.1 (0.6->4.0)
NA
EDEMA414
Randomized, double-blind, placebocontrolled
48
NA
29
Pooled data,
EDEMA2,
EDEMA4, DX
88/1915
All clinical trials that allowed openlabel dosing
179
NA
12
Icatibant
Ecallantide
Human recombinant C1-INH
Zuraw 201016
Randomized, double-blind, placebocontrolled (pooled data, two studies)
12
2.0 (1.2, 2.3)
NA
Riedl 201317
Open-label, single-arm, multicenter
62
1.0 (0.6, 1.3)
10
Riedl 201418
Randomized, double-blind, placebocontrolled with open-label extension
44
1.5 (1.0, 2.5)
9
a
N treated with study medication at approved dosage
b Reported as re-dosing with study drug or administration of rescue medication in studies allowing only a single dose of study medication
c 95% confidence interval
NA = not assessed or not available; TXA = oral tranexamic acid
Bold = lowest reported rate; used in formulas
Table 3. Per-attack cost estimation formulas for HAE products, factoring in patient weight and
re-dosing potential. Formulas allow insertion of institutional/facility-specific acquisition
costs per vial or syringe (italicized text).
Body Weight
Amount of Product required
Cost estimation formulaa
< 40 kg
800 IU = 2 vials
$(2 vials) + [$(2 vials) X .01]
75 kg
1500 IU = 3 vials
$(3 vials) + [$(3 vials) X .01]
100 kg
2000 IU = 4 vials
$(4 vials) + [$(4 vials) X .01]
125 kg
2500 IU = 5 vials
$(5 vials) + [$(5 vials) X .01]
Icatibant
Dose: 30 mg
How supplied: 30 mg syringe
Any
1 X 30 mg syringe
$(1 syringe) + [$(1 syringe) X .07]
Ecallantide
Dose: 30 mg
How supplied: 10 mg vial
Any
3 X 10 mg vials
$(3 vials) + [$(3 vials) X .12]
Product
pnfC1-INH
Dose: 20 IU/kg
How supplied: 500 IU vial
rhC1-INH
Dose:
BW <84 kg: 50 IU/kg
BW > 84 kg: 4200 IU
How supplied: 2100 IU vial
< 40 kg
2000 IU = 1 vialb
$(1 vial ) + [$(1 vial ) X .09]
75 kg
3750 IU = 2 vialsb
$(2 vials) + [$(2 vials) X .09]
100-125 kg
4200 IU = 2 vialsb
$(2 vials) + [$(2 vials) X .09]
a
Estimated need for re-dosing in a single attack: factors were 1% for pnfC1-INH, 9% for icatibant, 12% for ecallantide, and 9% for rhC1-INH,
based on lowest percentage available in published studies (see Table 1)
b Vial quantities rounded up to nearest whole vial
pnfC1-INH = pasteurized, nanofiltered C1-INH; rhC1-INH = human recombinant C1-INH
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