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Myeloma Drug Pricing But, with each new approval, price tags continued to climb, from $50,000 for a year’s supply of bortezomib to almost $200,000 for pomalidomide. 5 Although these prices are similar to those for therapies in other cancer types, certain aspects of MM escalate the financial burden of its treatment even further, according to Josh J. Carlson, PhD, MPH, of the Comparative Health Outcomes, Policy, and Economics (CHOICE) Institute at the University of Washington. “One of the big issues with pricing in myeloma is the doublet, and now triplet, therapies that are recommended as standard care,” Dr. Carlson said. “Using expensive combinations of drugs really drives up the price.” Also, because myeloma has no cure, many patients are advised to continue on these therapies as mainte- nance treatment. “They can be treated indefinitely,” Dr. Carlson said. “There are no clear guidelines on when to stop therapy, which, again, increases the treatment costs for any given patient.” Who Foots the Bill? Pharmaceutical manufacturers often downplay the high list prices by noting that patients don’t pay the full amount. Instead, they pay a portion through a copay or through coinsurance payments after their deductibles have been met. “With specialty drugs, a patient typically pays about 20% of the drug cost through coinsurance, until he or she reaches the out-of-pocket maximum for the year, which can be quite high,” Dr. Carlson said. “Then it all resets at the beginning of the next year.” However, the risks of financial toxicity are still high, even among patients with private insurance or Medicare. According to a 2015 survey of 111 myeloma patients, 71% reported at least a minor financial burden. 6 Almost half of patients (46%) were forced to dip into their savings, one- third (36%) to apply for financial assistance, and one in five (21%) to borrow money to pay for medications. Even if individual patients aren’t footing the bill for the entire cost of the drug regimen, someone else is cov- ering what they don’t pay. “Organizations may advocate for lower prices for my- eloma drugs, for lower out-of-pocket costs for patients, or for eliminating deductibles, but people have to keep in mind the overall cost to society,” said Vincent Rajkumar, MD, the Edward W. and Betty Knight Scripps Professor of Medicine at the Mayo Clinic in Rochester, Minnesota. For example, in the commercial space, when a health insurance plan has to cover the remaining costs of a medication, that expense ends up being spread out among all of the plan’s members through premiums, Dr. Carlson explained. As more money is spent on drugs, the premiums for health insurance rise. In employer-based plans, increasing premiums are often covered, at least in part, by the employers. “To cover these costs, employers are using money that could have been put into increased employee wages, rather than toward health insurance,” he said. In some cases, health insurers may benefit from prescription drug rebates – a complex and controversial topic itself. With prescription drug rebates, the drug manufacturer may provide a rebate to the PBM, which may share a portion of the rebate with the health insurer. These rebates serve as incentive for the PBM to include one product over another or to list that product in a preferred tier. 7 As evidenced by the Senate testimony that took place in April, regulators and legislators have called for more transparency about how these rebates are nego- tiated. Recently, the U.S. Department of Health and Hu- man Services (HHS) proposed a rule eliminating rebates. As HHS Secretary Alex Azar explained, this rule would 46 ASH Clinical News “end this era of backdoor deals in the drug industry … and deliver savings directly to patients when they walk into the pharmacy.” 8 A Value Proposition The cost of medication is not the only financial burden put on patients, noted Dr. Fonseca. “When patients live for many years, they have ex- penses associated with hospital stays, doctor visits, and medication copays, and many patients cannot continue working,” he said. “This creates a major strain on the finances of a household, which often has limited savings. The cost of drugs is only one part of the story.” A 2017 study by Dr. Fonseca and colleagues looking at trends in overall survival and costs of MM therapy bore that out: From 2000 to 2014, the percentage of patients with MM using a novel therapy increased from 8.7% to 61.3%, which was accompanied by substantial improve- ments in survival outcomes. 9 The new wave of FDA approvals in myeloma have successfully extended survival, but there are plenty of investigational drugs that never made it to market. The pharmaceutical industry argues that prices for ap- proved drugs are set high to recover the costs of failed drugs. According to the Pharmaceutical Research and Manufacturers of America (PhRMA), the trade organization representing biopharmaceutical research companies, research and development of a new medi- cine takes between 10 to 15 years and costs an average of $2.6 billion. 10 “This reasoning is a function of how hard it is to conduct clinical trials and how many different attempts companies have to make to bring a successful drug to market,” Dr. Carlson said. “They try to recuperate all failed attempts with a single successful attempt.” “The fact that pharmaceutical companies can price a drug high regardless of whether or not it is innovative or just a modification, like an analog rather than a new class of drugs, is the enemy of innovation.” —VINCENT RAJKUMAR, MD “It’s a little bit unfair just to look at the cost of the rela- tively few winners that you have in this business and say, ‘Aren’t you making a lot of money on those winners?’” Kenneth Frazier, CEO of Merck, told Harvard Business Review. “When in fact, in order to be a sustainable, ongo- ing business, you have to be able to pay for the cost of all those programs that inevitably don’t succeed.” The pharmaceutical industry is a business, and com- panies are beholden to shareholders who “keep giving us the capital to do the research that’s going to produce to- morrow’s drugs, while at the same time allowing patients and health systems to have access,” Mr. Frazier continued. In 2015, the FDA approved Merck’s PD-L1 inhibitor Keytruda (pembrolizumab) for advanced lung cancer, at a price of roughly $150,000 per year, per patient. When asked if he considered the cost reasonable, Mr. Frazier said, for patients who need pembrolizumab in this setting, “we’re talking about a life-and-death situation. … When you say the $150,000 for this successful drug doesn’t make sense, you have to realize that we’re actually paying for the 90% -plus projects that fail. Because we can’t have the winners if we’re not able to pay for the cost of the losers, so to speak.” This argument is harder to justify when one looks at some of the year-over-year price increases, however, Dr. Carlson said. A recent study looked at the contributions of both new and existing drugs to the changes in costs of oral and injectable brand-name drugs. 11 Between 2008 and 2016, the costs of oral brand-name drugs increased 9.2% annually, and the cost of injectables increased 15.1%. Ac- cording to the study, these increases were largely driven by existing drugs. Killing Competition There is also a lack of understanding about how drug prices are derived. According to Mr. Frazier, at Merck, determining the list price for a newly approved medica- tion involves asking first, “What is the value that this new medicine provides to patients and to the health-care system? … And the second [question asked] implicitly is, ‘What can patients and the health system afford?’” Pharmaceutical companies often fix their prices ac- cording to other available agents within that drug class. However, in the myeloma space, there is a definite lack of competition; the proteasome inhibitors are owned by two companies, and all three IMIDs are owned by the same company. Pharmaceutical manufacturers have been accused of using unsavory tactics to keep potential competitors at bay, which, in turn, keep prices high. For example, “product hopping,” also known as “forced switching” or “evergreen- ing,” involves companies issuing a reformulated version of a branded drug before the original product’s patent expires. Patients are switched to the reformulated drug that offers little to no therapeutic advantage over the original version, but it has an expanded patent, meaning a longer market exclusivity period. 12 If a generic version of the original drug becomes available after a clinician has switched to the new drug formulation, pharmacists cannot substitute the refor- mulated version for this generic because state laws allow for substitutions only when the dosage strength or other characteristics remain the same. Regardless, competition between companies does not always have a big impact on price, Dr. Carlson said. This is especially true with cancer therapies; even if patients receive one company’s drug as firstline treatment, they may use another company’s drug as second- or thirdline treatment. “In myeloma, because patients go through many sequences of drugs, the companies are not getting completely excluded [from the treatment plan]; they may just get a smaller market share,” he explained. “The health care marketplace doesn’t operate like a full free- market system.” The CEOs who testified before Congress earlier this year also justified the high costs of medicine on the com- plexities of the U.S. drug-pricing system. According to June 2019