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Steven Lucio, PharmD, BCPS
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Opportunities and Challenges in Biosimilar Uptake in Oncology
Carina Dolan, PharmD, BCOP

Opportunities and Challenges in Biosimilar Uptake in Oncology

Carina Dolan, PharmD, BCOP
There are now 10 approved biosimilars in the United States, including      3 oncology drugs, and at least 16 others in late-stage development. The introduction of competition into the biologic space launches a new era in the treatment of cancer, possibly increasing access to the extremely costly biologics. The most important and influential stakeholders for biosimilar acceptance and usage are healthcare providers, such as pharmacists and physicians, as well as patients. Gaining their support requires extensive education, postmarketing pharmacovigilance, resolving concerns about immunogenicity, and allowing interchangeability and substitution. Patients require education on the basic definition of biosimilars versus generic drugs, how biosimilars are tested and approved, costs, and availability of clinical trials. Meanwhile, payers may need to find ways to incentivize physicians to prescribe biosimilars over biologics, as well as to provide information on cost and quality directly to patients in order to drive uptake. Finally, legal challenges to approved and pending biosimilars have limited the market access of these agents.
Am J Manag Care. 2018;24(11):-S0
Since 2015, when the FDA approved the first biosimilar under the Biologics Price Competition and Innovation Act of 2009, 9 additional biosimilars have received agency approval, including 3 with an oncology indication.1 Although tbo-filgrastim was approved under the traditional drug approval pathway, many viewed this approval as an example of what biosimilars would look like in the United States following the first approved biosimilar in the European Union. By January 2018, at least 60 biosimilars were enrolled in the FDA’s biosimilar development program, with FDA commissioner Scott Gottlieb, MD, reporting that the agency had received requests for meetings to discuss biosimilars for 27 distinct reference biologics.2

Most recently, pegfilgrastim-jmdb was approved by the FDA to decrease the incidence of infection with febrile neutropenia in patients receiving myelosuppressive chemotherapy similar to its reference product. Bevacizumab-awwb, for the treatment of adult patients with certain colorectal, lung, brain, kidney, and cervical cancers; and trastuzumab-dkst, for the treatment of certain breast and stomach cancers, are approved biosimilars that will have the greatest impact in the oncology arena. The expected lower costs of these drugs are likely to increase access to these therapies, which are among the most expensive drugs in the United States and are often out of reach for the patients who need them most.3-5

The successful uptake of biosimilars in the practice of oncology, however, rests on numerous factors, involving clinicians, patients, payers, legislators, and manufacturers. These include the number and timing of entrants into the market; patient and provider acceptability; development costs; competition and litigation involving reference product manufacturers; market size and share; pricing; payer coverage and utilization policies; cost sharing; and regulatory policies around interchangeability (Figure 1).6,7

Clinician and Patient Uptake of Biosimilars in Oncology

The most important and influential stakeholders for biosimilar acceptance and usage are physicians and patients. However, there is evidence of significant gaps in knowledge for both audiences.

Physician Barriers

A survey of 376 US oncologists (part of a larger survey that included 1245 oncologists total from the United States, Europe, and Latin America) found that they lacked technical knowledge and understanding of the effects of biologics and biosimilars sharing the same nonproprietary name, and misunderstanding if biologics and biosimilars are structurally and therapeutically identical.8 Earlier surveys also found significant knowledge gaps regarding all aspects of biosimilars (chemical structure, difference from reference product, approval process, availability of biosimilars in the United States, etc) among clinicians of various specialties.9-12

Gaining physician support for and confidence in biosimilars will require evidence demonstrating that the biosimilar provides similar efficacy and safety to the reference product. Still, some aspects of the biosimilar concept remain unclear to practitioners surrounding the biosimilar approval process, required clinical trials, and pharmacovigilance. A 2018 statement by the American Society of Clinical Oncology (ASCO) on the appropriate use of biosimilars in clinical practice highlighted the need for postmarketing evidence development to enhance physician and patient confidence in their use. The authors noted that this was particularly important because regulatory review of biosimilars relies less on clinical data and more on structural, functional, and pharmacologic data. ASCO also noted the challenges of such postmarketing evidence, given the fragmentation of the US healthcare system. It suggested that its CancerLinQ database, which provides data on millions of de-identified patients, and the pending FDA surveillance system, Sentinel, designed to monitor safety issues in clinical trials, could be used to collect these data.13

As with any biologic, physicians also have concerns about immunogenicity. Given that biosimilars will, by necessity, be manufactured in a slightly different manner from their reference product, there is concern that switching patients from a biologic to a biosimilar, or vice versa, could result in hypersensitivity reactions. To evaluate that possibility, some clinical trials have included product switching, although assessing immunogenicity often depends on the molecule and the indications studied.14

An important issue affecting physician uptake of biosimilars is interchangeability and substitution. To receive interchangeability designation, the manufacturer must demonstrate not only that the biosimilar has similar efficacy and safety to the biologic, but also that there is no greater risk in switching between the biologic and biosimilar than remaining on the reference product.15 The advantage to the manufacturer is some level of exclusivity.16 The FDA announced a pathway to interchangeability in January 2017 and is expected to designate the first interchangeable products within the next 2 years.17

An interchangeability designation allows the biosimilar to be substituted for the reference product at the pharmacy level similar to the way generic products are substituted for brand drugs today. The physician can still reserve the right to designate the drug by name. Substitution, however, is controlled at the state level. By March 2018, nearly all states, the District of Columbia, and Puerto Rico had passed some type of legislation allowing substitution of biosimilars, although the details vary by state.18

The aforementioned survey of 376 US oncologists found that 80% believed it is critically or very important that they be notified if a biosimilar is substituted for the prescribed reference drug. They were also more likely than their Latin American or European peers to believe that patients could switch biologics mid-treatment and expect the same results.8

Early experience with the filgrastim biosimilar showed that providers were slower to incorporate biosimilars into their practice until they gained experience and felt comfortable prescribing the biosimilar. One health plan in the United States reported that 30% of filgrastim prescriptions were for the biosimilar, while another reported that prescriptions for the biologic had dropped by a third since the biosimilars entered the market, disclosing initial hesitation from oncologists to prescribe them. Today, many payers are beginning to give biosimilars preferred status on their formularies.19

Oncologists also tend to be more comfortable with trying new therapies for patients and adding newly approved drugs to their armamentarium fairly quickly. Moreover, practitioners are feeling pressure from patients about high-cost biologic therapies, causing many physicians to speak out about the cost of therapies.20

Patient Knowledge Gaps

Patients need to understand the concept of biosimilars and their place in the treatment continuum. To accomplish this level of awareness requires education, so patients can make an informed decision on their care. A 2015 American Autoimmune-Related Diseases Association survey of 362 of its members, 96% of whom have an autoimmune disease, found that more than 80% did not know what biosimilar medicines were, while about half understood the difference between biologics and biosimilars.21

In another consumer-focused survey from the consulting firm PricewaterhouseCoopers conducted in 2015, 67% of consumers did not know what a biosimilar was, while just 17% chose the correct definition from several choices.22

Patients require education on the basic definition of biosimilars versus generic drugs; how they are tested and approved; costs; and availability of clinical trials.14 The ASCO recommendations call for healthcare professionals to educate patients, and for medical societies, government sources, and patient advocacy organizations to provide public awareness and education programs, as well as use standardized, publicly available materials.13

Payers may also target patients directly with information about lower costs for biosimilars compared with the biologic medication. Medicare patients today pay a 20% co-payment for Part B drugs, which can be a significant cost for the higher priced biologics.23 In addition, a growing percentage of commercially insured individuals have high-deductible health plans.24 Thus, patients are becoming more aware of the cost of their healthcare.25-27

Payers and Reimbursement

The majority of cancer biologics are administered in an outpatient setting and paid for under the medical rather than pharmacy benefit (Part B for Medicare). Medicare typically reimburses for medication administered in a physician office or infusion clinic at a rate of the average sales price (ASP) plus 6% as an administrative fee.28 To incentivize the prescribing of biosimilars, CMS set the administrative fee for the biosimilar based on the ASP of the reference product plus 6% of the reference product’s ASP. How individual states will handle reimbursement under their Medicaid programs remains to be seen.29 Moreover, in January 2018, CMS finalized a ruling on the hospital outpatient prospective payment system (OPPS) for 340b hospitals, adjusting reimbursement to ASP minus 22.5%.30 This may impact the utilization of biosimilars in the ambulatory setting.

In the acute-care setting, biosimilars can be incorporated through the pharmacy and therapeutics (P&T) committee within the institution. This committee is primarily responsible for approving the pharmacy formulary system for the hospital and includes pharmacists, physicians, hospital administrators, nurses, and additional staff who support the medication use process. Many factors are taken into consideration when reviewing a drug to be placed on the formulary, including clinical effectiveness, operational objectives, cost, and product supply chain. Policies and procedures are approved that can include automatic substitution for medications to match the hospital formulary. Furthermore, the P&T committee can assist and direct staff educational programs that reflect changes to the formulary.

Additional payer reimbursement and requirements may also affect biosimilar uptake. Germany, which has one of the strongest uptakes of biosimilars in the world, incentivizes its doctors to prescribe biosimilars through quotas, budgeting, and monitoring programs, while key opinion leaders and medical associations provide education and integrate the use of biosimilars into their guidelines.30 Providing similar incentives for clinicians could drive uptake in the United States and, with the movement toward value-based reimbursement, may help drive the utilization of biosimilars. For instance, payers could offer higher in-office payments for clinicians who meet certain prescribing levels for biosimilars versus biologics.25

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