Economics of Intravitreal Medications for Neovascular AMD
Cost, VA improvement, and number of treatments factor into a balancing act.
ATUL JAIN, MD • NEETA VARSHNEY, MD
|Atul Jain, MD, is a vitreoretinal surgeon and partner at San Diego (CA) Retina Associates. Neeta Varshney, MD, is in private practice in San Diego. Dr. Jain receives research support from NIH and Regeneron and is a speaker for Regeneron and Alcon. Dr. Varshney has no relationships to disclose. Dr. Jain’s e-mail is email@example.com.|
Less than a decade ago, the goal of treatment for neovascular or “wet” age-related macular degeneration was, at best, a reduction in the rate of moderate to severe vision loss. Only for the past seven years have we been fortunate enough to have modalities available to us as retinal physicians to actually stabilize and improve visual acuity in patients with wet AMD.
In this article, we briefly compare the direct costs and efficacy of the various treatments available for wet AMD and delve further into how they play into the economics of a retinal practice.
SOMETHING IS BETTER THAN NOTHING
In 2005, the mainstay of treatment for wet AMD was photodynamic therapy with verteporfin (Visudyne, Valeant Ophthalmics, Bridgewater, NJ), with marginal benefits for particular subgroups compared to others (classic vs minimally classic vs occult neovascular membranes).
The bottom line is that PDT became an economic burden on patients and the health-care system, with the end result still loss of vision. With PDT, patients lost between 3 and 10 ETDRS letters over one to three years, with a mean VA loss of 8 letters.
Of course, this treatment proved superior to nonintervention, given that untreated eyes lost between 5 and 18 letters during the same period, with a mean VA loss of 14 letters.1–3
Matters of Cost
Each PDT treatment costs approximately $2,500: on average $1,400 for the medication, $500 for the physician fee, and $500/year for imaging.4 Patients required about four treatments per involved eye over a three-year period, with significantly fewer treatments thereafter.
Over three years, a patient on PDT therapy loses 6 fewer letters of VA compared to nonintervention, at a cost of approximately $10,000 (or $3,333/year). To simplify, if we say that observation results in 14 letters of VA loss, and PDT treatment is a 6-letter gain over observation (while still a net loss of 8 letters of VA), the cost of PDT is approximately $556 per letter of VA gained/year.
A treatment-naïve eye would experience a decrease in VA from 20/40 (Snellen) to 20/80+, while an eye that received treatment would decrease from 20/40 to 20/50-. We should also bear in mind that moving beyond three years, the number of PDT treatments required to maintain vision approaches zero.
THE DAWN OF ANTI-VEGF
By 2006, we had two anti-VEGF molecules available for the treatment of wet AMD: ranibizumab (Lucentis, Genentech, South San Francisco, CA) and bevacizumab (Avastin, Genentech).
These drugs were game changers for the treatment of wet AMD and the field of retina as a whole. Overnight, the goal of treating wet AMD became not only the prevention of central vision loss but also improvement in VA.
In the pivotal ANCHOR study,5 patients in the ranibizumab treatment group gained an average of 10 letters of VA, compared to a loss of 10 letters of VA in the PDT treatment group over two years.
Given this profound difference, PDT largely fell out of favor, and anti-VEGF medications became the new standard of care. Eyes previously treated with PDT that switched over to ranibizumab typically did not experience equivalent gains in VA as seen in eyes treated only with ranibizumab from the time of diagnosis.
Cost and Benefits
Approximately 21 intravitreal injections (IVI) of ranibizumab are necessary over a two-year period for patients to gain 10 letters of VA, compared to losing 10 letters with total of four PDT treatments over the same time period. Ranibizumab costs approximately $2,150 per dose (including the medication, physician injection fees, and OCT imaging).
Each eye treated with ranibizumab gains, on average, 20 letters of VA compared to PDT and 26 letters compared to observation, for a cost of $45,000 (or $22,500/year). The cost of ranibizumab treatment is approximately $868 per letter of VA gained/year compared to PDT, which costs approximately $556 per letter of VA gained/year, using the ANCHOR data.
Thus, a treatment-naïve eye would experience an increase in VA from 20/40 to 20/25, compared to a 20/40 eye decreasing to 20/60 with PDT treatment.
TABLE: Treatments for Neovascular AMD: Comparison of Cost and Efficacy
|Treatment||2-year cost||VA gain (net loss)||Injections required|
|PDT*||$8,000||(8–10 letters)||4 (IV)|
|Lucentis||$45,000||8 letters**||21 (IVI)|
|Eylea||$27,000||8 letters**||13.5 (IVI)|
|Avastin||$4,800||8 letters**||24 (IVI)|
*3-year cost. PDT treatment rarely goes beyond year 2, so costs approach $0.
**8 letters chosen as average based on numerous studies.
In 2011, the FDA approved aflibercept (Eylea, Regeneron, Tarrytown, NY) for the treatment of neovascular AMD. Soon thereafter, the New England Journal of Medicine published the results of the long-awaited Comparison of Age-Related Macular Degeneration Treatments Trial (CATT) study.6
Aflibercept, a soluble decoy receptor fusion protein that specifically binds to VEGF with a greater affinity than either bevacizumab or ranibizumab, in addition to placental growth factor (PlGF), was clinically equivalent to ranibizumab given every other month (after an initial three-month loading dose), compared to monthly ranibizumab.
After 96 weeks (~1.85 years), the aflibercept arm gained 7.6 letters, compared with a 7.9-letter gain in the ranibizumab arm, requiring 11.2 vs 16.5 injections, respectively (or approximately 12 aflibercept injections vs. 17.7 ranibizumab injections over a two-year period). Aflibercept costs approximately $2,000 (including the medication itself, physician injection fees, and SD-OCT imaging) per intravitreal dose.7,8
THE COST PARADIGM EVOLVES
Here, we begin to see a difference in costs: For two years of treatment with aflibercept for neovascular AMD, the cost is approximately $24,000, compared to $38,000 for ranibizumab, with clinically equivalent results in gains in visual acuity.
The difference in cost for one year of treatment between aflibercept and ranibizumab was roughly $7,000, when we examine the two-year study results aggregately. However, between weeks 52 and 96, only 4.2 aflibercept injections and 4.7 ranibizumab injections were necessary.
We must also bear in mind that ranibizumab has now received FDA labeling for a treatment interval beyond every four weeks (although it is stated that VA results can deteriorate with extension).
Accounting for these changes and mathematically extrapolating for year 2, roughly 4.8 aflibercept injections and 5.4 ranibizumab injections are required for the maintenance of VA gains from an injection burden of roughly seven aflibercept injections and 12 ranibizumab injections for the first year of the study.
The cost differential is most substantial during the first year of treatment, after which the two therapies become more similar. The first year of treatment costs $14,000 for aflibercept and $25,800 for ranibizumab, equaling average costs of $636 and $1,173 per letter of VA gained/year for aflibercept and ranibizumab, respectively.
For the second year (and theoretically all years moving forward), the costs are $436 and $528 per letter of VA gained/year for aflibercept and ranibizumab, respectively.
A treatment-naïve eye would experience an increase in VA from 20/40 to 20/25-, whether treated with ranibizumab or aflibercept, compared to a loss of VA to 20/60 with PDT, with an overall cost per letter gain over observation amortized over three years of $503 for aflibercept, $743 for ranibizumab, and $556 for PDT.
The Role of Bevacizumab
While bevacizumab has received broad off-label use for the treatment of wet AMD, its efficacy was not fully established until 2012, when the CATT results were released.6
At one year, bevacizumab dosed monthly was noninferior to ranibizumab dosed monthly. The bevacizumab group gained 8.0 letters of VA, and the ranibizumab group gained 8.5 letters, requiring 11.9 and 11.7 injections, respectively.
The cost of bevacizumab is approximately $180 (including the medication, physician injection fees, and OCT imaging) per dose. Extrapolating to two years, bevacizumab would require 24 injections at a cost of $4,320, resulting in VA gains of 8 letters. This makes the cost $98 per letter of VA gained/year for bevacizumab.
THE BIG PICTURE
We can assume a fixed cost of approximately $150 per IVI treatment visit for OCT testing and physician/injection fees. The cost of a compounded dose of bevacizumab (1.25 mg) is approximately $30, while aflibercept has a fixed cost of $1,850 per dose (2 mg), but the wholesale acquisition cost (WAC) and average selling price (ASP) are the same.
The WAC does not include any discounts or incentives, while the ASP includes virtually all of the available discounts averaged over all purchasers. Ranibizumab (0.5 mg) is more complicated because the WAC is $1,950 per dose, but the ASP was $1,909 in 2010 due to discounts from rebates given to high-volume purchasing organizations/practices.9
The average Medicare reimbursements per dose in 2012 were $61, $1,961, and $2,023 for bevacizumab, aflibercept, and ranibizumab, respectively. The reimbursement for aflibercept and ranibizumab was 6% greater than ASP (to cover overhead and storage fees).
However, after sequestration was implemented on April 1, 2013, the reimbursement decreased to 4.3% greater than ASP (Medicare reimbursement decreased by 2% for the 80% portion of drug costs that Medicare pays, while supplemental or beneficiary insurance continues to cover the full 20% of the ASP).
As a result, the reimbursements for aflibercept and ranibizumab are now approximately $1,930 and 1,991, respectively. The reimbursement for bevacizumab has not yet changed. What does this mean for a retinal practice?
Affordable Care Act and Anti-VEGF
The profit margins for administration of intravitreal bevacizumab will remain largely unchanged after health-care reform at approximately $30 per dose. Profit per dose of aflibercept will decline from $111 to $80, or by roughly 28%.
Ranibizumab, again, is more complicated because of the rebate program offered for this medication. High-volume practices can receive a rebate of up to 3.5% of the WAC of ranibizumab. Translated, a practice that receives no rebate will have a profit of $41 ($73 pre-sequestration) per dose of ranibizumab, while a practice receiving the maximal rebate will realize a profit of $109 ($141 pre-sequestration).
SEEING THE FUTURE
Over the past 15 years, the treatment of wet AMD has gone from a loss of 14 letters (observation) of VA to a gain of 8 letters (IVI of anti-VEGF medications) — that is, a difference of 22 letters. This equates to change from baseline VA of 20/40 resulting in 20/80 vs. 20/25-, for observation and IVI, respectively.
We have gone from minimizing the severity of vision loss to gaining vision! But this gain comes at a cost of approximately $100, $500, and $700 per letter of VA gained/year for bevacizumab, aflibercept, and ranibizumab, respectively. RP
1. Blinder KJ, Bradley S, Bressler NM, et al. Treatment of Age-related Macular Degeneration with Photodynamic Therapy Study Group; Verteporfin in Photodynamic Therapy study group. Effect of lesion size, visual acuity, and lesion composition on visual acuity change with and without verteporfin therapy for choroidal neovascularization secondary to age-related macular degeneration: TAP and VIP report no. 1. Am J Ophthalmol. 2003;136:407-418.
2. Treatment of Age-related macular degeneration with Photodynamic therapy (TAP) Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of 2 randomized clinical trials — TAP report. Arch Ophthalmol. 1999;117:1329-1345.
3. Verteporfin in Photodynamic Therapy Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in pathologic myopia with verteporfin. 1-year results of a randomized clinical trial--VIP report no. 1. Ophthalmology. 2001;108:841-852.
4. Brown MM, Brown GC, Lieske HB, Lieske PA. Preference-based comparative effectiveness and cost–effectiveness: a review and relevance of value-based medicine for vitreoretinal interventions. Curr Opin Ophthalmol. 2012;23:163-174.
5. Brown DM, Kaiser PK, Michels M, et al; ANCHOR Study Group. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1432-1444.
6. CATT Research Group; Martin DF, Maguire MG, Ying GS, Grunwald JE, Fine SL, Jaffe GJ. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med. 2011;364:1897-1908.
7. Heier JS, Brown DM, Chong V, et al; VIEW 1 and VIEW 2 Study Groups. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology. 2012;119:2537-2548.
8. Gragoudas ES, Adamis TP, Cunningham ET Jr, Feinsod M, Guyer DR; VEGF Inhibition Study in Ocular Neovascularization Clinical Trial Group. Pegaptanib for neovascular age-related macular degeneration. N Engl J Med. 2004;351:2805-2816.
9. Levinson DR. Medical Payments for Drugs Used to Treat Wet Age-related Macular Degeneration. Washington, DC; Department of Health and Human Services; 2012.