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WHEN CHOICE ARRIVES: Competition & Consequences

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BIOSIMILAR APPROVALS

Skylar Jeremias is the Managing Editor for The Center for Biosimilars and The American Journal of Managed Care (AJMC).

Articles

New Danish registry data confirm the safety of switching to infliximab biosimilars, showing low rates of serious adverse events in patients with inflammatory arthritis.

Danish Registry Analysis Finds Consistent Safety After Switching to Infliximab Biosimilar GP1111

A new study confirms KM118, a proposed biosimilar to pertuzumab, shows pharmacokinetic similarity and safety, paving the way for affordable HER2-positive breast cancer treatments.

Early Evidence Supports KM118 as a Biosimilar to Reference Pertuzumab

The US biosimilar market evolves with 90 approvals, significant price drops, and new PBM models enhancing access to cost-effective therapies.

Milestone Approvals, Evolving PBM Models May Redefine the 2026 Biosimilar Landscape

Alex Keeton serves as the executive director of the Biosimilars Council.

FDA Draft Guidance on Biosimilars Is a Win for Patients; Now Congress Must Finish the Job

The Center for Biosimilars connects professionals with insights on biosimilars, health economics, regulatory outcomes, and emerging treatment paradigms.

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1rem

In this special video episode of Not So Different, co-hosts Giuseppe Randazzo and Alex Keeton from the Association of Accessible Medicines tackle the FDA's recent draft guidance on comparative efficacy studies (CES) and interchangeability for biosimilars, addressing some of the confusion around the new announcement and remaining action items for the agency.

All Things Biosimilars: How Streamlined CES Rules Could Shift the Market

Chelsee Jensen, PharmD, BCPS, senior pharmacy specialist and pharmaceutical formulary manager at Mayo Clinic, shared her insights on future biosimilar development amidst recent FDA approvals and policy changes.

In an interview with The Center for Biosimilars

 (CFB), Jensen expanded on how recent changes in the biosimilar landscape might affect payers and patients.

This transcript was lightly edited for clarity. 

CFB: Given that roughly 90% of biologics coming off‑patent may lack a biosimilar, what proactive strategies should health systems adopt now to safeguard patient access and cost containment?

 From a health system perspective, this is a really challenging area because, as costs stay high, reimbursement might not always cover that medication expense from a health system perspective. I think for health systems to keep providing care without taking on major losses, we need to have effective site-of-care management strategies in place and strong contracting skills. The most cost-effective strategy for health systems may be to join forces and advocate with manufacturers, nonprofits, and coalitions to develop biosimilars, especially where spending is high and competition is limited. 

Additionally, I do think incentives are needed to encourage biosimilar development and help lower the overall cost of health care. This could require financial support from the federal government and nonprofit organizations.

It is promising to see that there has been a recent legislative change and efforts aimed at reducing biosimilar development costs by limiting some of those comparative effectiveness studies, especially when that robust analytical data is there to support it. However, I think challenges will still remain, since it is still quoted that the cost to develop a biosimilar in the US ranges anywhere from $75 million up to $250 million.

I think we do have a way to go, from a health care system perspective; the best we can do is create those coalitions so we can try to incentivize the development of biosimilars in some of those vacant categories.

 simplifies analytical comparability and clinical bridging. Which specific elements do you think will most accelerate time-to-market for future biosimilars?

The advancement of analytical technologies that are able to detect those differences or similarities with greater accuracy, and when combined with expanded access to sensitive measurement tools, will enhance the reliability of that analytical data. This improvement is expected to diminish the reliance on those in human trials and therefore reduce or lower the development costs. By having these superior technologies, we should be able to see earlier submissions of biologic license applications (BLAs), potentially leading to expedited approvals and accelerated markets.

 of multiple denosumab biosimilars in a single year shows rapid market expansion. What lessons can be drawn from that experience for upcoming biosimilar launches in other high-revenue biologics?

The recent guidance update that removed the requirement for the comparative effectiveness switching studies to achieve interchangeability designations does mark significant progress and has positively impacted the denosumab category, likely encouraging greater adoption. I think this category is particularly noteworthy as well, because denosumab is predominantly a medical benefit drug, though there might be some pharmacy benefit coverage as well, and it mainly affects older adults, where we see more government-insured, Medicare, or Medicare Advantage payer populations.

Here at Mayo Clinic, we're really focused on learning how we can more effectively manage biosimilar switches and biosimilar adoption by utilizing our electronic health record tools and exploring ways to enhance category flexibility through the electronic health record moving forward; meaning, with the product we change, how can we rapidly incentivize and do proactive conversion? And when we do have that flexibility down the road, should the contract change while we're still under negotiation in this category?

I do suspect that most health care institutions may choose to contract with 1 manufacturer for both Prolia and Xgeva (denosumab; Amgen) biosimilars. However, because there's such strong competition in this category, it could be that we select one manufacturer for its Prolia biosimilar and another manufacturer for its Xgeva biosimilar, also in this category. It's not new, because Prolia and Xgeva have always shared the same Healthcare Common Procedure Coding System code. We are seeing that same trend with the biosimilars.

However, there’s still a need to keep a pulse on this, making sure that we're not running into any downstream billing errors and denials because of that shared fixed code. [We should continue] to rely on that provider education and how we build these on the electronic health record to make sure that we are selecting the appropriate product for the appropriate indication.

CFB: When several biosimilars compete for the same reference product, what criteria (clinical data, pricing, real-world evidence, patient-support programs) become most decisive for formulary placement at Mayo Clinic?

At Mayo Clinic, at this stage, we really have a high level of confidence in the clinical data coming from the process for a vast majority of the biosimilar assets. I think the final decision will likely depend on factors such as supply resiliency, manufacturer reputation, and history and pricing, because in the denosumab categories, specifically, this is a heavy government population, and I don't think co-pay assistance really plays a role here, as we know that many of our government programs are exempt from co-pay assistance for assistance programs.

However, other categories that are coming out, like omalizumab, Xolair biosimilars, natalizumab, and Tysabri biosimilars, do have a higher volume of commercially insured populations, and therefore copay assistance and payer coverage are some aspects that I do expect would be important considerations for those categories, but not really a focus for the denosumab category.

CFB: What early warning signals does Mayo Clinic monitor to anticipate a ‘biosimilar void’ for a specific reference product, and how do those signals shape your formulary strategy?

Where we're really pivoting here at Mayo Clinic is [finding] a more robust way to monitor the financial performance and outcomes of our whole drug portfolio. We really worked on internal tools to track our drug costs, our reimbursement, and broader financial trends more efficiently. That way, we can determine where we are having reimbursement issues, and we're able to dig in. Is this due to a denial or to a prior authorization issue that maybe we can update within the electronic health record, or [something to] discuss with our providers? Or is this because our reimbursement is simply not covering our costs? Therefore, is the average sales price far below what we have to purchase the drug at?

When we get into those later line agents, of course, we'll try to negotiate and try to get better pricing on the drug, but this is where we're really seeing that biosimilar void. I know we can't get any better pricing. I know this drug is off patent, and we don't have any competition coming. And that's really where we have to have some of those other harder discussions, saying, What else can we do in this category? Could we potentially start partnering with a coalition (eg, Cost Plus, Civvica) or some of our other coalitions to really incentivize the development of these drugs?

Lowering that development cost because of the greater good that we need this type of drug in the US market, and that's where we're going. Where I think this biosimilar void does factor in is if we're not seeing any competition. This is really where healthcare institutions may have to make difficult decisions to move these drugs out to 340B facilities, or if they're an orphan drug, disproportionate share hospitals, and that's where access really could get limited for patients, and that's really where I hope we don't have to go in the market. But I’m sure that is where some health care institutions currently are in decisions that they might be facing right now.

Mayo Clinic’s Chelsee Jensen, PharmD, discusses FDA policy changes, biosimilar development hurdles, denosumab lessons, and payer access strategies.

Q&A With Chelsee Jensen, PharmD: FDA Policy Shifts, Biosimilar Development Hurdles, and Market Access in 2026

Stakeholders across the US health care system navigated a maturing biological market that reached a significant milestone of 90 total approvals by the end of 2025.

 This progress, detailed in a recent industry report from Samsung Bioepis, highlighted how the biosimilar sector moved beyond early-stage growth into a complex era of high market penetration and shifting financial incentives.

As of December 2025, the FDA had cleared biosimilars for 20 unique biological molecules, with 63 of those 90 approvals (70%) successfully reaching the commercial market. These launches led to substantial price reductions over time; on average, the average sales price for biosimilars decreased by 52% within 5 years of the initial class launch. In more mature therapeutic areas, these price reductions reached as high as 77%.

Market adoption patterns revealed a distinct divide between "fast" and "slow" uptake markets. Oncology, ophthalmology, and pegfilgrastim biosimilars were categorized as fast-uptake products, achieving an average market share of 81% within 5 years of launch. In contrast, sectors such as immunology, filgrastim, and insulin glargine saw much slower adoption, averaging only a 25% market share in the same timeframe. By the third quarter of 2025, specific molecules like bevacizumab and trastuzumab reached biosimilar market shares of 92% and 88%, respectively.

Despite these gains, the industry faced significant issues regarding traditional pharmacy benefit management (PBM) contracting. Historically, the PBM model favored high-wholesale acquisition cost (WAC), high-rebate products because those products contributed more heavily to the "rebate guarantees" that PBMs promised to self-funded employers. This structure created a "rebate trap" where a lower-cost biosimilar might have a lower net price than the reference biologic but was excluded from formularies because it did not provide the necessary rebate volume to satisfy aggregate contractual guarantees.

In 2026, however, the report pointed to a critical shift toward fiduciary and transparent PBM models. These emerging frameworks prioritized trend management and cost control over rebate maximization. Some PBMs introduced "rebate credits," which allowed the price difference between a reference product and a biosimilar to count as a "phantom credit" toward rebate guarantees, effectively removing a major barrier to biosimilar adoption.

Thomas Newcomer, vice president and head of US commercial operations at Samsung Bioepis, commented on these systemic changes in the report's press release: “As the US healthcare market enters 2026, stakeholders’ approaches to prescription drug pricing and management continue to evolve. Alongside established PBM contracting structures, new models emphasizing alternative pricing reimbursement, transparency, and a shift towards more fiduciary responsibility have emerged in response to changing market conditions.”

Specific therapeutic areas also faced unique challenges as 2026 began.

 In the ophthalmology space, although 4 aflibercept biosimilar products are awaiting clearance to launch, the reference product faces only 1 competitor offering a 12% WAC discount. Meanwhile, the immunology sector saw a proliferation of complex pricing strategies; while private label brands became common for adalimumab and ustekinumab, most ustekinumab manufacturers avoided the dual "high WAC/low WAC" strategy that characterized the adalimumab market in previous years.

Looking forward through 2026, the continued erosion of reference product dominance appeared likely as PBMs pledged fuller rebate pass-throughs by 2028 and more employers adopted biosimilar-first strategies.

 These shifts suggested that the primary challenge for the industry was no longer demonstrating clinical parity but rather aligning financial incentives to ensure that the most cost-effective therapies reached the patient.

Biosimilar approvals. The Center for Biosimilars

. Updated December 22, 2025. Accessed January 27, 2026. 

https://www.centerforbiosimilars.com/biosimilar-approvals

SAMSUNG BIOEPIS: Biosimilar market report 12th edition, Q1 2026. January 23, 2026. Accessed January 27, 2026.

Samsung Bioepis releases Q1 2026 US biosimilar market report. News release. Samsung Bioepis. January 23, 2026. Accessed January 27, 2026. 

https://www.samsungbioepis.com/en/newsroom/newsroomView.do?idx=531&currentPage=1

Jeremias S. Happy birthday adalimumab biosimilars: reflecting on the first year of US competition. The Center for Biosimilars. January 31, 2024. Accessed January 27, 2026. 

https://www.centerforbiosimilars.com/view/happy-birthday-adalimumab-biosimilars-reflecting-on-the-first-year-of-us-competition

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Qilu Pharmaceutical, Mabpharm, Bio-Thera Solutions

Henlius, Innovent Biologics, Bio-Thera Solutions

Test your knowledge of biosimilar approvals in China.

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Efforts to expand access to vision-saving therapies for people with diabetic eye disease increasingly depend on the availability of lower-cost biologic alternatives, and new comparative data add clarity to how one aflibercept biosimilar performs in routine clinical practice. A recently published retrospective analysis evaluated whether the aflibercept biosimilar QL1207 offered similar outcomes to reference aflibercept for individuals with diabetic macular edema (DME), a leading cause of vision impairment among people with diabetes.

The study was conducted to address a longstanding gap in real-world data. Although QL1207 was approved by China’s National Medical Products Administration in late 2023 based on structural and functional similarity to reference aflibercept, published comparative clinical information in DME populations remained limited. 

Given the high cost of originator anti-VEGF therapy and the chronic, injection-intensive nature of DME management, the investigators sought to determine whether the biosimilar performed comparably in anatomical and functional outcomes, macular perfusion metrics, injection burden, and safety.

The analysis included anonymized clinical data from 80 adults (80 eyes) with nonproliferative diabetic retinopathy and DME who were seen at a single ophthalmology department between June 2023 and April 2024. Participants were treatment-naïve and met diagnostic criteria outlined in the American Academy of Ophthalmology’s 2019 clinical guidelines. Individuals were excluded if they had other retinal diseases, a history of ocular procedures, proliferative disease, significant media opacity, or a hemoglobin A1c greater than 7%.

Demographic characteristics were balanced across treatment groups. The reference aflibercept group included 40 people (20 men and 20 women) with a mean age of 48.6 years. The QL1207 group included 40 people (19 men and 21 women) with a mean age of 46.7 years. Baseline HbA1c levels were similar, and no clinically meaningful differences emerged during the 12-month follow-up period.

All participants received 3 monthly loading doses followed by a pro re nata retreatment approach. Retreatment criteria included central retinal thickness (CRT) greater than 280 µm or a decrease of 5 or more Early Treatment Diabetic Retinopathy Study letters. Best-corrected visual acuity (BCVA), optical coherence tomography measures, and optical coherence tomography angiography parameters—including foveal avascular zone (FAZ) area and superficial and deep vascular density (SVD and DVD)—were collected at baseline and during follow-up. The investigators also recorded injection frequency and adverse events.

The study found no statistically significant differences between groups in BCVA or CRT at baseline or at 1, 3, 6, or 12 months. Both groups demonstrated significant improvement in BCVA relative to their own pretreatment values, as well as substantial reductions in CRT (

 < .05 for all within-group comparisons). At 12 months, mean CRT decreased from 447.1 µm to 280.4 µm in the reference group and from 441.0 µm to 290.3 µm in the QL1207 group. Injection burden was also similar, with mean injection counts of 3.58 in the reference group and 3.40 in the biosimilar group (

Macular microvascular outcomes also aligned closely across groups. FAZ area decreased significantly within each group, while both SVD and DVD increased, indicating improved or stabilized macular perfusion. None of these parameters differed significantly between groups at baseline or month 12.

Safety outcomes were consistent with the known safety profile of intravitreal anti-VEGF therapy. Mild events—including transient intraocular pressure elevations, corneal epithelial damage, and subconjunctival hemorrhage—occurred infrequently and at similar rates in both groups. No individuals experienced endophthalmitis, glaucoma, vitreous hemorrhage, cataract progression, or systemic cardiovascular or cerebrovascular events during the follow-up period.

The authors noted several limitations, including the retrospective design, relatively small sample size, nonrandomized treatment assignment, and 12-month follow-up period. In addition, while statistically significant changes in OCT angiography parameters were documented, their clinical significance remains uncertain. Longer, prospective, randomized studies will be needed to validate long-term comparability between QL1207 and reference aflibercept in DME.

Even with these limitations, the findings contribute to growing real-world evidence showing that aflibercept biosimilars may offer an effective and potentially more affordable option for individuals living with DME. As biosimilar adoption grows globally, studies like this may help inform formulary decisions and support broader access to sight-preserving therapy.

Zhai G, Liu N, Wang S, Zhang X. Comparative efficacy of intravitreal aflibercept biosimilar QL1207 versus reference aflibercept in the treatment of diabetic macular edema. 

. 2025:12:1662735. doi:10.3389/fmed.2025.1662735

Clinical

Biosimilar QL1207 Demonstrates Equivalent Efficacy and Safety in DME

In 2009, Congress created a regulatory pathway for biosimilars to encourage competition and address rising spending on biologic drugs. One barrier to adopting biosimilars in the US is that the FDA has traditionally required additional testing for biosimilars to be deemed interchangeable with the original biologic. This analysis reviews the history and current status of biosimilar regulation in the US, concluding that changing the FDA’s interchangeability standards—as proposed by some policy makers—is a potentially useful but likely insufficient step to improve biosimilar competition in the US. Other policy options include more state laws allowing pharmacists to automatically substitute biosimilars, addressing strategies by payers and pharmacy benefit managers that inhibit biosimilar competition, and implementing more widespread education of clinicians and patients to build confidence about biosimilars. Other policies to ensure the affordability of biologic drugs include expanding Medicare’s price negotiation to cover biologics with or without biosimilar competition.

Congress created an expedited approval pathway for biosimilar drugs to compete and lower costs of biologic medications, but biosimilar use has been characterized by slow uptake.

Currently, not all biosimilars are deemed interchangeable with the original biologic, and some policy makers have proposed changing the biosimilar interchangeability laws to improve competition in the biosimilar market.

Such a change is a useful first step, but other changes are needed, including amending state laws to allow greater automatic pharmacist substitution, addressing strategies by payers and pharmacy benefit managers that inhibit biosimilar competition, and ensuring more education of clinicians and patients to build confidence about biosimilars.

Biologic drugs—complex products often synthesized from living cells—make up only 2% of prescriptions in the US but account for approximately half of prescription drug spending.

 To address these high costs, Congress passed the Biologics Price Competition and Innovation Act (BPCIA) in 2009. This law created a framework for the FDA to approve biosimilars, which are biologics made by different manufacturers with no clinically meaningful differences from already-approved biologic drugs.

 The goal was to spur competition between biosimilars and biologics to lower costs, just as generic competition has done for small-molecule drugs. In the decade after the passage of the BPCIA, however, the biosimilar marketplace was characterized by delays in biosimilar approval and availability, slow biosimilar uptake,

Challenges to biosimilar competition include limited interchangeability and lack of automatic pharmacist substitution. The FDA certifies nearly all generic drugs as therapeutically equivalent to the original brand-name drugs, and state laws allow—and often mandate—pharmacists to substitute therapeutically equivalent generics in place of brand-name drugs.

 This automatic pharmacist substitution facilitates rapid adoption of generics.

 By contrast, the BPCIA set additional standards for biosimilars to be deemed interchangeable with the originator biologic, and most state pharmacy substitution laws are more restrictive for biosimilars than generics.

 In recent years, the evidence required by the FDA to meet the interchangeability standards has evolved, and some at the FDA have proposed eliminating the separate interchangeability designation entirely.

 Improving the interchangeability of biosimilars could enhance biosimilar uptake in the US, although additional steps are needed to unlock further savings for patients and the health care system.

The BPCIA required the FDA to affirm that biosimilars have no clinically meaningful differences and are as safe and effective as the original biologic. In practice, this has meant that biosimilars are typically tested in head-to-head randomized clinical trials against the original biologic for at least 1 of the drug’s indications. By contrast, the bioequivalence determinations for generic small-molecule drugs are based on more limited pharmacokinetic and pharmacodynamic data from small studies of healthy volunteers.

For biosimilars to be designated as interchangeable, the FDA requires evidence that a biosimilar could be expected to yield the same results as the original biologic for any individual patient and that switching between the biosimilar and the original poses no additional concerns related to safety or diminished effectiveness. This was initially operationalized via switching studies run by biosimilar manufacturers that evaluated safety and efficacy when patients alternated between a biosimilar and its reference product.

One of the primary motivations for a separate interchangeability standard was concerns that minor differences between biologics and biosimilars could lead to antidrug antibodies when patients switch versions, which could diminish the effectiveness or lead to adverse effects through cross-reactivity with patients’ own proteins. These concerns were based on rare reports of treatment failure related to antidrug antibodies.

 Regulators in other countries, including the European Medicines Agency, did not include similar 2-tier regulatory systems for biosimilars,

 although automatic pharmacist substitution is not standard practice in these countries.

The FDA approved the first biosimilar in 2015, but it was not until 6 years later that the FDA approved the first biosimilar with an interchangeability designation, a version of long-acting insulin glargine-yfgn (Semglee) deemed interchangeable with the original version (Lantus). As of May 2025, the FDA has approved 75 biosimilars, 21 of which were granted interchangeable designations.

Recently, US regulators have signaled a shift in their approach to biosimilar interchangeability. In June 2024, the FDA released an updated draft guidance that eliminated the expectation for switching studies.

 The FDA defended this change based in part on a meta-analysis conducted by FDA scientists that revealed no differences in safety or immunogenicity among patients switching from a reference biologic to a biosimilar.

 These conclusions aligned with those from extensive postmarketing analyses conducted in the European Union and the global experience,

 reinforcing that the FDA’s “highly similar” standards for biosimilars were sufficient for determining interchangeability.

In response to shifting FDA guidance, some policy makers have proposed that Congress alter the BPCIA to eliminate the separate interchangeability standards.

 Such a policy was included in the Biden administration’s 2024-2025 fiscal year budgetand was publicly supported by some leaders at the FDA.

One goal of removing the separate interchangeability designation for biosimilars is to boost competition and further lower costs for biologic drugs in the US. This could be accomplished if the streamlined regulatory standards encourage more drugmakers to introduce biosimilars or if the improved interchangeability standards promote greater uptake of biosimilars by patients.

Key Barriers and Solutions Beyond Interchangeability

Even if Congress were to remove the interchangeability designation, competition in the biosimilar marketplace in the US could be further optimized by addressing state pharmacist substitution laws, reimbursement behavior by pharmacy benefit managers (PBMs), and skepticism from patients and clinicians. Simultaneously, it is sensible to enact alternative policies to ensure the affordability of biologic drugs after patent protection expires, such as expanding Medicare’s price negotiation to cover biologics with or without biosimilar competition.

 The rules about whether pharmacists can (or must) automatically substitute biosimilars in place of the original biologic are set by state legislatures in their oversight of the practice of pharmacists. For generics, substitution laws have been remarkably effective. Generics are used 97% of the time when available, and generic uptake is lower when state substitution laws are more restrictive.

After Congress passed the BCPIA, many state pharmacy substitution laws were modified to allow pharmacist substitution of FDA-designated interchangeable biosimilars. However, these laws were often stricter than the same state’s laws governing generic substitution; for example, many states required physician notification if a pharmacist substituted FDA-approved biosimilars.

 Additionally, unlike the FDA’s generic therapeutic equivalence designations, interchangeable biosimilar designations only apply between each biosimilar and the original drug—the FDA does not certify that 2 biosimilars for the same drug are interchangeable. It remains unclear whether state laws would allow substitution between multiple biosimilars of the same drug.

Thus, current state substitution laws may undermine rapid biosimilar uptake, particularly if these laws do not permit substitution between different biosimilars of the same biologic drug. Even if Congress revises the FDA’s interchangeability standards, it is ultimately up to state lawmakers to determine the role of pharmacists in expanding biosimilar use.

 For pharmacists to freely substitute FDA-approved biosimilars, payers and their PBMs would need to adjust reimbursement policies to be agnostic to which version of a biologic drug patients receive. For generic drugs, public and private payers usually reimburse pharmacies based on a maximum allowable cost schedule, which incentivizes pharmacies to dispense the lowest-cost generic version.

By contrast, PBMs have generally treated biologics and biosimilars separately, negotiating rebates and formulary position with each manufacturer, similar to how they handle competition among multiple brand-name drugs in the same class. Thus, even if biosimilars are interchangeable, pharmacists must fill whichever version is preferred by a patient’s insurance formulary. Additionally, biologic manufacturers can leverage their rebates to block biosimilar competitors.

 For example, several biosimilar versions of the blockbuster drug adalimumab (Humira) entered the market in 2023. However, brand-name Humira continued to account for more than 98% of adalimumab prescriptions, likely because AbbVie offered substantial rebates to PBMs to maintain Humira’s advantage over biosimilars.

In August 2023, CVS Caremark, one of the 3 largest PBMs in the US, announced that it would stop covering Humira and instead cover a biosimilar that it would produce via a comarketing arrangement with the drug’s manufacturer. Three PBMs account for approximately 80% of all prescriptions in the US,

 so if other PBMs pursue a similar comarketing strategy, this could mean that only a limited number of biosimilar makers are able to secure such contracts and market their products successfully in the US. These arrangements may result in short-term savings for patients and the health system, but a market characterized by such agreements might dissuade companies from investing in developing future biosimilars without assurance that their product will generate sufficient sales to cover these costs.

Some members of Congress have asked federal regulators to scrutinize comarketing agreements between PBMs and biosimilar makers for anticompetitive behavior.

 Additionally, state and federal policy makers could consider prohibiting confidential rebates for biologic drugs once biosimilar versions become available in the US to improve price transparency and facilitate more direct price competition. For federal programs such as Medicare, this may require Congress to revise the safe harbor protections that currently exempt rebates from federal antikickback statute. For clinician-administered drugs, CMS could revise its Part B reimbursement rules to create bundled payment rates for biologics and biosimilars, like the current reimbursement rules for generics.

 A prerequisite for relying on pharmacist substitution to facilitate a competitive biosimilar marketplace is that patients and prescribers be comfortable freely switching between versions, even after they have initiated treatment. Switches between generic drug manufacturers are commonplace; although these changes are safe and effective,

 patients who experience a change in the size, shape, or color of their medication (eg, because they receive a version made by a different manufacturer) are more likely to stop taking it.

For biosimilars, regulators in the US and internationally have not found evidence that switching between versions poses risks in terms of safety or effectiveness. Still, surveys of prescribers have shown varying degrees of confidence; some prescribers have expressed concerns about patients switching to a biosimilar after achieving clinical stability with the original biologic.

 Although these concerns are well intentioned, they raise a fundamental question about whether prescribers (and patients) would accept widespread automatic biosimilar substitution. If regulations and laws allowed pharmacist substitution only for new users, for example, this would dramatically limit the ability to rely on substitution to promote competition between biologics and biosimilars.

Although FDA regulators are convinced that switching between different versions of a biologic is safe, more evidence or better communication of existing evidence is needed to educate patients and clinicians. Similar knowledge barriers existed in the early days of generics, when patients and clinicians expressed skepticism about the safety and efficacy of generic medications. Even as late as 2009, 23% of physicians surveyed harbored doubts about the effectiveness of generics, and 50% had concerns about their quality, leading more than 25% to avoid recommending generics as first-line therapy.

 Overcoming these barriers will require robust educational campaigns for patients and prescribers.

 Competition from low-cost generics has been remarkably effective in lowering costs of small-molecule drugs, in large part due to interchangeability and pharmacy substitution. If the same approach proves insufficient for biologic drugs, another option is regulation of prices after a period that allows biologics to earn sufficient sales revenue to recoup research and development costs. The Inflation Reduction Act of 2022 allows Medicare to negotiate prices for certain drugs and includes a statutory minimum price reduction of 60% lower than the nonfederal average manufacturer price after a drug has been on the US market for 16 years.

 Currently, Medicare’s ability to negotiate prices ends once generic or biosimilar competition begins, but Congress could amend this to continue leveraging Medicare’s negotiation authority to lower biologic prices rather than relying solely on biosimilar competition.

Changing the FDA’s interchangeability standards is a necessary step to improve biosimilar dissemination in the US market and thereby increase competition, reduce prices, and improve access to these medications. However, such a policy change would likely be insufficient on its own to optimize the uptake and affordability of biologic medications. So far, the evidence supports the safety and effectiveness of switching between a biologic and its biosimilars, but additional evidence and guidance from regulatory bodies, including the FDA, could help build confidence among providers and patients, which could pave the way for more flexible state pharmacy substitution laws. Policies are also needed to prevent payers and PBMs from inhibiting biosimilar competition and potentially to ensure that biologic prices fall after a period, regardless of biosimilar competition.

 Program On Regulation, Therapeutics, And Law (PORTAL), Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School (BNR, AB, ASK), Boston, MA.

 This project was funded by a grant from Arnold Ventures.

 Dr Rome and Dr Kesselheim have received consulting fees from Alosa Health and grant funding from the Elevance Health Public Policy Institute and the National Academy for State Health Policy. Dr Kesselheim has served as an expert on behalf of a class of payers in a case against Johnson & Johnson relating to patents on the biologic drug Stelara and on behalf of the Federal Trade Commission in a case against pharmacy benefit managers. Ms Bhaskar reports no relationship or financial interest with any entity that would pose a conflict of interest with the subject matter of this article.

 Concept and design (BNR, AB, ASK); drafting of the manuscript (BNR, AB); critical revision of the manuscript for important intellectual content (BNR, AB, ASK); obtaining funding (ASK); administrative, technical, or logistic support (AB); and supervision (BNR, ASK).

 Benjamin N. Rome, MD, MPH, Brigham and Women’s Hospital Division of Pharmacoepidemiology and Pharmacoeconomics, 1620 Tremont St, Ste 3030, Boston, MA 02120. Email: brome@bwh.harvard.edu.

The U.S. Generic & Biosimilar Medicines Savings Report

. Association for Accessible Medicines; September 2023. Accessed January 18, 2025. 

https://accessiblemeds.org/wp-content/uploads/2024/11/AAM-2023-Generic-Biosimilar-Medicines-Savings-Report-web.pdf

2. Implementation of the Biologics Price Competition and Innovation Act of 2009. FDA. Updated February 12, 2016. Accessed January 18, 2025. 

https://www.fda.gov/drugs/guidance-compliance-regulatory-information/implementation-biologics-price-competition-and-innovation-act-2009

3. Rome BN, Bhaskar A, Kesselheim AS. Use, spending, and prices of adalimumab following biosimilar competition. 

. 2024;5(12):e243964. doi:10.1001/jamahealthforum.2024.3964

4. Hong D, Kesselheim AS, Sarpatwari A, Rome BN. Biosimilar uptake in the US: patient and prescriber factors. 

5. Feng K, Russo M, Maini L, Kesselheim AS, Rome BN. Patient out-of-pocket costs for biologic drugs after biosimilar competition. 

. 2024;5(3):e235429. doi:10.1001/jamahealthforum.2023.5429

6. Sacks CA, Van de Wiele VL, Fulchino LA, Patel L, Kesselheim AS, Sarpatwari A. Assessment of variation in state regulation of generic drug and interchangeable biologic substitutions. 

. 2021;181(1):16-22. doi:10.1001/jamainternmed.2020.3588

7. Rome BN, Lee CC, Gagne JJ, Kesselheim AS. Factors associated with generic drug uptake in the United States, 2012 to 2017. 

. 2021;24(6):804-811. doi:10.1016/j.jval.2020.12.020

Changing the FDA biosimilar interchangeability standards is a necessary but likely insufficient step to improve biosimilar competition in the US.

Alex Keeton

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