Inmaculada Hernandez, PharmD, PhD; Samuel W. Bott, BS; Anish S. Patel, BS; Collin G. Wolf, BS; Alexa R. Hospodar, BS; Shivani Sampathkumar, BS; and William H. Shrank, MD, MSHS
The unsustainable rising prices of specialty drugs have prompted a debate about how medications are priced. Manufacturers contend that high prices are essential to recoup research and development costs; however, a growing societal chorus believes that manufacturers are maximizing profits at the expense of patients and the healthcare system. Concerns about drug pricing policies are amplified in oncology and hematology,1-6
where vulnerable patients and their families often have unrealistic expectations about the value of treatment.7
Of note, the mean price of a cancer drug has doubled in the last decade, and targeted therapies represent an important driver of this increase.1,7,8
In this study, we compared the annual price of monoclonal antibody (mAb) therapies approved in the last 20 years by the FDA across disease states. Specifically, we evaluated whether the prices were higher for mAbs used in cancer than for those used in other disease states. We limited our analysis to mAbs to minimize the potential impact of varying production costs among different types of molecules.
We identified all indications approved by the FDA for mAbs from 1997 to 2016 using the FDA website.9
After excluding radioactive mAb–indication combinations (n = 1), antidotes (n = 1), and those approved for diagnostic purposes (n = 3), withdrawn from the market by 2016 (n = 2), or not available to the public for other reasons (n = 2), our sample included 107 unique mAb–indication combinations (eAppendix Table 1
[eAppendices available at ajmc.com
]). From the FDA-approved label of each mAb, we extracted the recommended dose for each indication, chemical structure (whole mAb, antigen-binding fragment antibody, or other), source (human, humanized, chimeric, or murine), and route of administration (subcutaneous, intravenous, intramuscular, or intraocular). We categorized indications into 5 disease states: oncology or hematology, cardiology or endocrinology, immunology, infectious diseases or allergy, and ophthalmology. We further classified oncology and hematology indications into 7 categories: bone cancer; breast cancer; gastrointestinal cancer; lung, head, or neck cancer; melanoma; hematologic malignancies and hematologic disorders; and other types of cancer, which included glioblastoma, metastatic renal cell carcinoma, urothelial carcinoma, and neuroblastoma (details in Figure
We extracted the US average wholesale price per milligram as of January 2017 from UpToDate10
and calculated the annual price of treatment for a standard patient—a 70-kg/1.80-m adult, a 40-kg patient in the case of mAb–indication combinations approved for juvenile conditions (ie, with childhood onset), or a 4.5-kg infant for mAb–indication combinations used in pediatrics (ie, for diseases that occur in the first weeks of life)—for each mAb–indication combination as the product of the recommended dose for 1 year of treatment and the price per milligram. We used lower-bound values for the weight of a standard patient because dosing is based on weight only for some mAbs, so using a higher value would increase the probability of type I error when comparing prices of mAbs that require dose adjustment with those that do not.
We constructed generalized linear models with gamma distribution and log link to evaluate how the annual price of treatment differed across disease states. We controlled for route of administration, chemical structure, time since FDA approval, and source, all of which can
affect production costs.11
We followed the same methodology to examine how pricing of oncology and hematology mAb–indication combinations differed by type of cancer or hematologic disorder. All analyses were conducted at the mAb–indication combination level, meaning that for mAbs approved for more than 1 indication, each indication counted as a separate observation (details in Table [part A and part B]
Our sample included 107 mAb–indication combinations, with a mean (median) annual price of $96,731 ($58,968). The annual price of treatment exceeded $100,000 for 34 (32%) mAb–indication combinations and was highest for 2 indications of eculizumab ($800,280 for atypical hemolytic uremic syndrome and $592,654 for paroxysmal nocturnal hemoglobinuria) and lowest for denosumab, which is indicated for fracture prevention ($2465) (eAppendix Table 1). The annual price of treatment was highest for mAbs used in oncology or hematology (median, $142,833; interquartile range [IQR], $73,920-$164,291], followed by immunology (median, $53,969; IQR, $28,056-$68,770) (Figure and eAppendix Table 2
). Of 43 oncology and hematology mAb–indication combinations, 29 (67%) were priced higher than $100,000 per year of treatment. Although oncology and hematology mAb–indication combinations represented only 40% of all mAb–indication combinations approved in the last 20 years (43 of 107), they accounted for more than 85% of those priced $100,000 or higher (29 of 34). Within oncology and hematology indications, the annual price of treatment was highest for mAbs indicated for types of cancer delineated as “other,” which included glioblastoma, metastatic renal cell carcinoma, urothelial carcinoma, and neuroblastoma (median, $167,152; IQR, $158,456-$230,225), followed by lung, head, or neck cancer (median, $163,746; IQR, $162,086-$181,417).
After adjusting for route of administration, source, chemical structure, and time since FDA approval, the annual price of oncology or hematology mAbs was $149,622 higher than those used in cardiovascular or metabolic disorders; $98,981 higher than in immunology; $128,856 higher than in infectious diseases or allergy; and $106,830 higher than in ophthalmology (all P
<.001) (Table). Other than disease state, the chemical structure of a mAb was the only factor significantly associated with pricing. In subgroup analysis, we found no significant differences in prices of mAbs by type of cancer or hematologic disorder, which was probably due to the small sample size of each group, as well as the large price variability of hematology mAbs.
Our analysis is the first to compare the price of mAbs approved by the FDA in the last 20 years across disease states. Our results document the high prices of this type of medication; with an average price of $96,731, the annual price of treatment exceeded $100,000 for 32% of 107 mAb–indication combinations approved by the FDA between 1997 and 2016. Oncology and hematology mAbs represented 40% of the combinations approved, yet they accounted for more than 85% of those priced $100,000 or higher. After adjusting for factors that can affect production costs, we found that mAb therapies approved for the treatment of cancer and hematologic disorders are around $100,000 per year of treatment more expensive than mAbs used in other disease states.
Higher prices for mAbs used in oncology and hematology may be explained by multiple factors. First, in order to recover development costs, manufacturers set higher prices for drugs used for a short period of time or for drugs indicated in rare conditions. This likely explains why the 2 most expensive mAb–indication combinations were those with eculizumab, originally approved for paroxysmal nocturnal hemoglobinuria, which affects only 5000 patients in the United States.12
In addition, duration of treatment is usually shorter in cancer, where drugs are commonly used for weeks or months, than in other disease states where drugs may be used for years. Second, the therapeutic arsenal available for the treatment of some types of cancer and hematologic disorders is narrower than in other disease states, which makes patients and providers less responsive to the prices of these medications. Third, payers have limited levers to restrict access to, and hence lower prices for, cancer drugs.6,13
This is because Medicare Part D plans are required to include all cancer drugs in their formularies and some states also mandate the coverage of cancer drugs by private insurers.6,14
This study was designed to describe patterns in pricing and did not aim to assess the process manufacturers apply when determining the asking price for their medications. Moreover, our study did not attempt to assess the value of the agents studied in terms of cost-effectiveness or clinical outcomes. In addition, our study did not evaluate the pricing of targeted therapies other than mAbs, and we used average wholesale prices, which do not account for manufacturers’ rebates. Nevertheless, this does not invalidate our results because the objective of our study was not to estimate net drug prices after discounts but to compare prices across disease states, and rebates should not differ across disease states.
Despite these limitations, our study has important implications. At a time when healthcare resources are constrained and threaten state and federal budgets, the rapidly rising costs of prescription drugs, specialty drugs in particular, will continue to garner media and policy attention.7
In the absence of some type of value framework where prices are justified by the value they bring to specific patients or the population, attention to drug pricing is likely to grow. There may be a unique opportunity for clinical experts and manufacturers to collaborate and redefine how the value of pharmaceuticals is measured and fundamentally shift the way manufacturers are reimbursed for high-cost medications like mAbs.5,15-17