Tony Hagen is senior managing editor for The Center for Biosimilars

Boehringer Ingelheim believes it is on its way toward gaining perhaps the first interchangeable designation for a biosimilar, based on 

, a phase 3 randomized study that compared pharmacokinetic properties for the adalimumab reference product (Humira, RP; 40 mg/0.8 mL) with those of the adalimumab biosimilar Cyltezo (BI 695501) in patients with moderate-to-severe chronic plaque psoriasis.

Patients received RP continuously or switched between the biosimilar and RP, and investigators concluded that patients who were switched multiple times between RP and Cyltezo experienced similar clinical outcomes in terms of pharmacokinetics, efficacy, immunogenicity, and safety.

“This study is, to our knowledge, the first to report outcomes that meet the US FDA’s criteria for interchangeable biologic designation,” investigators stated in findings presented at the American Academy of Dermatology 2021 virtual meeting this month.

There are 29 FDA approved biosimilars but none of them has an interchangeable designation, meaning that, depending on individual state laws, pharmacists could fill prescriptions with biosimilars rather than the originator product without approval from the prescribing physician. It is generally assumed that the lack of interchangeable designations is a chief impediment to patient and physician confidence in biosimilars, which are FDA approved as being “highly similar” to originator brands, and just as safe and efficacious, with no clinically meaningful differences.

For an interchangeable designation from the FDA, a biosimilar is “expected to produce the same clinical result as the reference product in any given patient” and “not present greater risks in terms of safety or diminished efficacy from alternating or switching between the interchangeable candidate and reference product,” Boehringer Ingelheim noted, quoting from FDA guidelines.

Cyltezo was approved in 2017 and is scheduled for launch on July 1, 2023, based on a settlement with AbbVie. Boehringer Ingelheim anticipates an FDA decision on the application for interchangeability in the fourth quarter of 2021.

In VOLTAIRE-X, investigators evaluated area under the curve (AUC), or drug concentration over time in the bloodstream; Cmax, or peak concentration after administration of the first dose; presence of anti-drug antibodies (ADAs), a measure of immunogenicity and the body’s response to adalimumab; and presence of neutralizing antibodies (nAbs), which can diminish or boost biosimilar effectiveness.

They randomized 238 patients to the switching (n = 118) or continuous treatment (n = 120) arms. In the switching and continuous treatment cohorts, the adjusted mean AUC was 2025.83 μg.h/mL vs 1925.90 μg.h/mL, respectively (ratio of adjusted means, 105.19%; 90.2% CI, 96.58-114.64).

Adjusted mean Cmax was 7.08 μg.h/mL and 7.00 μg.h/mL in the switching and continuous arms, respectively (ratio of adjusted means, 101.14%; 90.2% CI, 93.26-109.70). Investigators concluded the 90.2% CIs for AUC and Cmax were within the acceptable bioequivalence boundaries of 80% to 125%.

In the evaluation for immunogenicity, investigators found that at week 32 similar proportions of patients had developed ADAs in the switching vs continuous treatment arms (90.2% vs 94.5%, respectively), and nAb results were similar also between the 2 arms (41.1% and 41.8%, respectively).

In the switching vs continuous treatment arms, the proportions of patients who achieved a psoriasis area and severity index (PASI) score of 75 (75% or better showing improvement over baseline PASI scores) were also similar: 84.7% vs 79.0%, respectively (90% CI, –2.45%-13.96%).

The proportions of patients with physician global assessment (PGA) scores ≤1 at week 32 were also similar between the switching and continuous treatment arms: 70.3% vs 64.7%. The PGA is 5- to 6-point measure for disease severity.

On safety, investigators noted that following randomization, the percentages of patients who experienced at least 1 treatment emergent adverse event (TEAE) were similar in both arms (56.8% and 62.5%, respectively). A slightly higher percentage of patients experienced drug-related TEAEs in the continuous treatment arm (18.3% vs 11.9%).

Menter A, McCabe D, Lang B, et al. Phase III, randomized trial comparing clinical outcomes between patients with moderate-to-severe chronic plaque psoriasis receiving adalimumab reference product continuously versus those who switched between BI 695501 and adalimumab RP. Presented at: American Academy of Dermatology 2021; April 23-25, 2021. 

Articles

American Academy of Dermatology

The results of Voltaire-X could persuade the FDA to authorize automatic substitution of the adalimumab biosimilar Cyltezo for its reference product (Humira), investigators believe. 

Cyltezo Is a Contender for First Interchangeable to Humira, Boehringer Ingelheim Says

An ongoing real-world observational study of bevacizumab biosimilar (Mvasi) vs originator (Avastin) has demonstrated comparable safety and effectiveness for a cohort of patients with metastatic colorectal cancer (mCRC) treated in a US integrated health care system (Kaiser Permanente), according to a poster presentation at the Academy of Managed Care Pharmacy (AMCP) 2021 meeting. 

Patients were enrolled in the study based on initiation of biosimilar bevacizumab between July 1, 2019 and March 30, 2020 (n = 232) or initiation of bevacizumab reference product between July 1, 2015 and June 30, 2018 (n = 1128).

The primary end point was overall survival (OS) and mortality, and secondary end points were treatment persistence, defined as the total number of doses received, time between first and last dose, and the proportion of patients who switched to the reference product. Other secondary end points were the incidence of serious adverse events (SAEs) and hospitalizations and emergency department visits of any type.

Investigators said OS for the bevacizumab biosimilar cohort (82.8%) was noninferior to that of the reference product group (81.7%), based on a 4% margin of acceptability. They said that between the 2 groups, there were no significant differences in treatment persistence, SAEs, or hospitalizations and emergency department visits.

They said the study successfully captured real-world outcomes for patients treated with bevacizumab biosimilar immediately after the product was launched. They also said a strength of the study was its use of a large historical control group. Limitations of the study included that it was observational, which is not considered as reliable as a clinical study, and that it had a relatively short follow-up period, investigators said.

Pham C, Chiu T, Ekinci E, et al. Real-world evaluation of biosimilar bevacizumab-awwb versus bevacizumab in patients with metastatic colorectal cancer in a U.S. integrated healthcare delivery system. Presented at: AMCP 2021; April 12-16, 2021. Accessed April 23, 2021. https://amcpannual2021.pathable.co/organizations/7nYnTLzA3j3JZpccw#/?limit=10&sortByFields[0]=isPinned&sortByFields[1]=lastActivityAt&sortByOrders[0]=-1&sortByOrders[1]=-1&uid=pAcLoMw6BXog7ypr6

AMCP: Academy of Managed Care Pharmacy

Investigators tapped health system data to conduct an observational, real-world comparison of bevacizumab (Mvasi) vs the reference product (Avastin). 

Kaiser Permanente Study Demonstrates Equivalence for Mvasi

It’s going to be an issue for accessibility of medicine if competing companies won’t produce biosimilars of drugs that aren't as lucrative as biosimilars of blockbuster medicines, a panel of European experts said at the Medicines for Europe Biosimilar Medicines Virtual Summit 2021.

“It’s well known that development costs of biosimilars are very high compared with the development costs of generics,” said moderator Adrian van den Hoven, director general of Medicines for Europe. “Are we, in Europe, going toward a market where biosimilars will be up only against very big blockbuster biologics, whereas the smaller, more medium-size biologics won’t be worthwhile?” he asked.

In Denmark, the market for biosimilars is small (population 6 million), and yet there has been robust interest from biosimilars developers. Health authorities have to be careful not to get into a situation where prices are too low that companies might withdraw their bids to supply biosimilars, said Dorthe Bartels, senior strategic advisory at Amgros, the national procurement organization for Denmark. 

However, she said, a positive sign is that in China many companies are developing biosimilars for a broad range of biologics that are not limited to the most lucrative of biologics. 

Given the high cost of developing biosimilars, manufacturers might have minimum sales revenues requirements, which could preclude them from producing biosimilars for relatively minor indications, said Phillip van Wilder, a professor at Université Libre de Bruxelles School of Public Health in Belgium. This issue is connected to the problem of sustainability of biosimilars and needs to be part of the general discussion, “because it’s something where resilience is necessary,” he said.

Europe may be perceived as a place where biosimilars have in general been widely accepted, compared with the United States, and yet biosimilar success varies across EU member states. Panelists discussed the value of “top down” approaches to impose the use of biosimilars where market dynamics appear not to be working.

The European Union as a whole cannot force the use of biosimilars on member states, but it can influence biosimilar uptake via recommendations issued to countries that receive money from the European Union, van den Hoven said. “Many EU countries are now in the situation where they are receiving recommendations from the [European Commission], so should the commission be recommending or telling member states “you should have more biosimilar competition in your market?” he asked.

Bartels said that based on the Denmark experience, it might be better to use an education approach to communicate to stakeholders the gains that have been achieved by using biosimilars. For example, in Denmark, the country has achieved an initial 85% discount on the cost of originator adalimumab. “In the rheumatoid arthritis area, around 15% more patients have gained medicine, because we have introduced biosimilars, so maybe the story should be around the success of introducing biosimilars and the treatment for patients,” she said.

Have conversations with physicians and patients about switching to biosimilars and provide information that supports this education and influences behavior.

Use a top-down policy approach that provides a structure for biosimilar uptake.

Plan everything over time so everybody is prepared, because then you have people with you instead of against you. And you can do things regionally, nationally, or even in just one hospital.

Use a holistic approach that incorporates biosimilar company contracts (tenders), hospital finances, communication, and quotas.

A somewhat authoritarian policy that imposes biosimilar uptake could be of value in some Central Europe countries where biosimilar competition has not evolved as hoped, said panelist Tomas Tesar, an associate professor of pharmacy with Comenius University in Slovakia. There tends to be segmentation in these markets where originator biologics end up not competing head-to-head with biosimilars. “These are issues which could be solved by a top-down approach,” Tesar said.

Biosimilars have been approved as monotherapies for various indications, but more and more, pharmaceutical companies are developing combination medicines, and the panel viewed this as an opportunity to channel more biosimilar use, because these combinations of 2 or more drugs, which end up getting approved by regulators, could include 1 or more biosimilars from the get-go. The use of biosimilars has the potential to bring down the cost of these combination therapies. “We’ve seen in some countries, mainly in the United Kingdom, that expensive innovator compounds used in combination with biosimilar versions are cost-effective and are therefore accessible to the patients,” van den Hoven said.

This is happening in Denmark, Bartels said. Biosimilar use is written into applications for marketing of biologic combinations. “I think that’s actually the way forward. It will be cheaper for all of us.”

Combining innovator products with biosimilars as a concept appealed to other members of the panel. However, “we need to find a policy in which there is at least some competition in the market between various providers of the same products,” van Wilder said.

European countries have tender systems that allow drug companies to bid to obtain near exclusive license to supply drugs, although countries also work with multi-tender agreements that allow more than 1 supplier. In Denmark for adalimumab, although it is a small country, the tender was awarded to 2 bidders because of concerns that a single supplier might not be able to supply the whole market consistently. For now, that’s the only multi-supplier arrangement in Denmark, Bartels said, but it’s possible it might be tried with other drugs.

Europe has biosimilars approved for 17 different originator drugs, and another 30 innovator biologics are expected to lose market exclusivity over the next 10 to 15 years, according to IQVIA. Van den Hoven asked the group to speculate whether or not the next wave of biosimilars can be incorporated into practice with greater ease than the ones that came before.

Ireland is still on the beginning end of the biosimilar adoption curve, said Bernard Duggan, a chief pharmacist with Trinity Centre for Health Sciences at St James’ Hospital in Dublin. “We’ve come a long way in the last 2 years.” That experience likely could make uptake of the next series of biosimilars much swifter, he said. “I supposed we’ve learned a lot as we’ve gone through the process. It’s not one-size-fits-all. There will be slight nuances that need to be considered, but I think we have a framework here now that, if we’re called upon again, could be used to promote further uptake of other biosimilar medicines.”

Medicines for Europe  Biosimilar Medicines Conference

The European Union is a diverse market with pockets of biosimilar resistance but also cost-saving triumphs, panelists said at the Biosimilar Medicines Virtual Summit 2021.

Medicines for Europe Panel Tackles Biosimilar Uptake

Editor's note: This is part 1 of a series on biologics patents and biosimilars.

The biosimilars pathway in the Biologics Price Competition and Innovation Act (BPCIA) was created to address the needs of biosimilar applicants and speed their products to market for the benefit of patients, but is the pathway working?

Panelists at the Festival of Biologics USA meeting said some tinkering may be necessary to optimize the patent resolution process (aka patent dance) in the BPCIA, particularly when it comes to understanding processes and intellectual property related to manufacturing.

The BPCIA was created in 2010 by legislative fiat, but “whether it’s working or not depends on what expectations you have of the system and how you expected it to work over time,” said Hans Sauer, vice president for Intellectual Property at the Biotechnology Innovation Organization. “The BPCIA as it’s currently interpreted and implemented is perhaps not quite what I and others expected when it was first passed.”

Compared with the 1984 Hatch-Waxman Act for simple molecule chemical compounds (generics), there are more moving parts to the BPCIA. During the patent dance, biosimilar developers and originator companies come to the fence to decide where potential intellectual property infringements may occur and attempt to resolve those issues prior to the biosimilar being launched. It’s one of the vital organs of the BPCIA.

“The patent dance is working for people who chose to use it, right? And it’s not working if litigants make different choices. Does that mean it’s a train wreck? I don’t know,” Sauer said. “I think we see a greater diversity of corporate behavior, of litigation behavior, than certainly what we see in the small molecule space. If you have an expectation that this is supposed to work like the Hatch-Waxman system for small molecules, it does not. It’s certainly working for litigants who have come out on top and who end up getting out of the system what they want, but for the other guys, it’s usually not working.”

The beauty of the patent dance is its flexibility, said Timothy “Tim” J. Shea Jr, biotechnology intellectual property expert and director of Sterne Kessler Golstein and Fox of Washington, DC. “It’s not a one-size-fits-all, as maybe we are more likely to see under Hatch Waxman, and so we see a lot of different strategies in terms of the patent dance and other aspects of the statute.” The BPCIA allows biosimilar applicants to choose the order of battles that are most important to them. “If there are certain patents that are going to drive the decision of whether to launch or when to launch, being able to focus on those early on, I think, is very positive,” he said.

But would more information on manufacturing patents and processes, disclosed earlier, help biosimilar applicants get more products to market faster and with less trouble? Legislation has been drafted to prompt more disclosure from reference product manufacturers to improve clarity and, ultimately, to make the marketplace more competitive. And in December 2020, the Biological Product Patent Transparency Act was signed into law, requiring originator product companies to promptly share relevant patent information with the FDA. Starting in June 2021, this disclosed information would automatically be entered in the Purple Book reference guide for the biologics industry.

However, the risk is that manufacturers burdened with greater disclosure requirements would be fearful of sharing manufacturing secrets and become less willing to innovate, panelists said. “These innovations are extremely valuable, not just to the biosimilar applicant but to the whole industry, and we want to encourage that,” Shea said. “I don’t like the idea of a kind of a draconian provision that just says all this must be disclosed.”

It’s also possible that disclosure requirements could make the process more confusing for the originator product companies, besides too revealing, Sauer said. “If I sit on a portfolio of alternative resins for chromatography columns, columns for purification, or alternative cell culture media that could be used, or others, which do I disclose? The ones that I use may not be the ones the biosimilar company ends up using."

Legislation has raised the specter that companies that fail to sufficiently disclose the patents they hold may lose the right to enforce those patents in the event of infringement. “List it or lose it propositions that we’ve seen throughout these bills have been our greatest concern,” Sauer said. Another reason originator manufacturers may be leery of disclosure laws is that the intellectual property may pertain to multiple products the company produces. Revealing information about one product may compromise another.

One way to enhance the information exchange might be to start the patent discussion earlier in the application process, even several years before anticipated approval and launch of a biosimilar, said Bruce Leicher, moderator of the panel and a strategic law advisor and adjunct processor in Biotechnology Law at the University of New Hampshire Franklin Pierce School of Law.

For that to work, the timing has to be right, said panelist David Korn, vice president of Intellectual Property and Law with PhRMA, a pharmaceutical industry trade association. “Is it that, at some point, it becomes too early to actually engage the full process and the back and forth, and if there are any changes after that, then it would seem like the whole thing needs to be restarted in order to get a true picture of the patents that are relevant to that particular biosimilar.”

Shea agreed that the timing should be worked out so that discussions over intellectual property occur when it’s relevant to have them. “I think you do want to be at a point where the process is fixed enough that it just really makes sense, otherwise it opens up all sorts of cans of worms in terms of being premature.” But an earlier discussion of relevant patents has the potential to “reduce the surprise element for the biosimilar applicant,” he said.

Ultimately, biosimilar developers ought to have a good sense of what information is needed to understand where infringements may lie, Sauer said. After all, they have developed their own manufacturing processes by the time they apply to the FDA for approval. “To my mind, the biosimilar developer is best positioned to know what to look for in the published patent literature and published application literature,” he said. 

“Why is it that we so persistently hear concern about the uncertainty that’s being caused by manufacturing patents?" he asked. "Is it that manufacturers keep getting new patents to improve manufacturing technology that pop out of the system when it’s too late? Is it that biosimilars are genuinely locked into a limited range of technologies, and they discover that all of this ends up being patented by someone?”

Festival of Biologics

More disclosures, earlier in the biosimilar application process, might lead to more competition in biologics, but panelists said this could go too far.

Panel: Should Biologics Manufacturers Have to Disclose More About Their Patents?

Investigators found inferior persistency among patients who used biosimilar vs originator forms of infliximab (Remicade) and epoetin alfa (Epogen/Procrit), although they said adherence was superior among patients on biosimilars included in the study, according to a poster presentation at AMCP 2021.

Investigators conducted a retrospective study using patient information culled from the Optum specialty pharmacy database, representing a 2-year period from January 2018 to December 2019. Investigators defined persistency as “continuation of treatment for the prescribed period” and adherence as the patient acting in accordance with prescription intervals and prescribed dosage.

The percentage of patients who remained on biosimilar infliximab dipped below 20% by the fifth prescription fill, whereas the percentage who remained on the originator product remained above 20% by at least the ninth fill, according to study authors.

The percentage who remained on epoetin alfa biosimilars dipped below 40% around the third fill, whereas patients on the originator did not dip below the 40% line until the fifth fill.

For patients treated with filgrastim and pegfilgrastim biosimilars, the persistency curves were slightly inferior to originator persistency, although these differences were not considered statistically significant. “Patients in reference drugs had higher persistence at every fill compared to biosimilars. However, significant difference in persistency was seen only between the Remicade and Epogen/Procrit groups,” the authors wrote.

However, when it came to adherence, patients in all therapy groups studied adhered better to biosimilars than reference products and had lower out-of-pocket costs if they used biosimilars, the authors wrote.

For example, adherence for patients on Inflectra and Renflexis, both biosimilars of Remicade, had 93% vs 90% adherence, respectively. The comparable figures for patients on filgrastim biosimilar (Zarxio) vs originator (Neupogen) were 81% and 60%; pegfilgrastim biosimilar (Udenyca, Fulphila) vs Neulasta, 93% vs 86%; and epoetin alfa biosimilar (Retacrit) vs originator (Epogen/Procrit), 88% vs 83%.

The largest per-fill out-of-pocket differences were seen for filgrastim biosimilars vs filgrastim originator ($102 vs $383) and pegfilgrastim biosimilars vs originator ($79 vs $376).

A higher incidence of adverse events was reported for patients on biosimilars for all groups except pegfilgrastim; however, investigators said they were unable to evaluate or categorize adverse events according to severity.

“The findings of this study reflect the positive real-world implications of utilizing biosimilars from a cost-adherence standpoint,” the authors wrote.

The data from the study were obtained from Optum and Avella Specialty Pharmacy, which was acquired by Optum in 2018. “Data collected from only 1 specialty pharmacy may not represent the general population in the United States,” investigators said.

Shah K, Lawler L. Real world evidence: impact of biosimilars on patient outcomes at a specialty pharmacy. Presented at: AMCP 2021; April 12-16, 2021. Accessed April 19, 2021. https://amcpannual2021.pathable.co/organizations/Yxzi8AFuWFPvqnPR2#/?limit=10&sortByFields[0]=isPinned&sortByFields[1]=lastActivityAt&sortByOrders[0]=-1&sortByOrders[1]=-1&uid=pAcLoMw6BXog7ypr6

Weaker persistency and strong adherence were observed among patients taking biosimilar forms of epoetin alfa and infliximab, among others.

Study: Investigators Report Superior Adherence, Savings for Biosimilars

Magellan Rx Pharmacists Discuss Why All Biosimilars Are Not Added to Formularies 

Magellan Rx Pharmacists: Why Payers Should Be More Invested in Promoting Biosimilars

Magellan Rx Pharmacists: Current Biosimilar Market Trends in Oncology

Magellan Rx Pharmacists: What Disease States Have Better Biosimilar Uptake?

Magellan Rx Pharmacist: How to Encourage Payers to Prefer Biosimilars

Magellan Rx Pharmacists: Which Formulary Placement Is Most Beneficial for Biosimilar Uptake?

Magellan Rx Pharmacist: What Is the Cure for Rebate Addiction?

Magellan Rx Pharmacists: What the US can Learn from Europe's Biosimilar Industry

Magellan Rx Pharmacists: What Can Payers Do to Boost Biosimilar Uptake?

Magellan Rx Pharmacist: Cost Savings Potential if Oncology Biosimilar Utilization Increased

Videos

Rebecca Borgert, PharmD, BCOP, and Jim Rebello, PharmD, from Magellan Rx Management talk about how market trends, payer formulary decisions, and international successes are shaping today's biosimilars industry.

Magellan Rx Pharmacists Explore the Payer Perspective on Oncology Biosimilars

Using commercial and public payer data, investigators observed that payer utilization management policies such as step therapy contributed to a sizeable movement toward biosimilar use, according to a poster presentation at AMCP 2021.

“Payers equipped with proactive utilization management strategies for oncology biosimilars were able to capitalize on early utilization shifts to the less expensive biosimilar products,” the authors concluded.

They conducted a retrospective claims analysis for patients with cancer enrolled in commercial and Medicare plans between June 2019 and June 2020. They evaluated the transition to biosimilars from 3 originator products Avastin (bevacizumab), Herceptin (trastuzumab), and Rituxan (rituximab).

The authors of the study also found that, in some cases, physicians were ahead of the curve in prescribing biosimilars and switching patients from originator products to biosimilars, meaning payer coverage preferences did not force them.

Additionally, physicians in private practices were twice as likely to independently switch patients to biosimilars than their counterparts in outpatient hospitals (279 vs 131 switches, respectively, for 5374 prior authorizations).

The study also included a model of savings that could be achieved from biosimilar use based on the utilization and pricing data included. For example, use of originator bevacizumab was associated with an extra $35.6 million in spending compared with use of bevacizumab biosimilars, based on overall costs of 20,076 claims.

The comparable excess spending for trastuzumab originator was $11.7 million for 25,511 claims and $19.9 million for rituximab originator based on 9275 claims.

However, they cautioned that “true savings” could not be determined because variable rebate arrangements between payers and manufacturers made it challenging to calculate.

The study evaluated formulary policies across 16 commercial and 12 Medicaid Advantage plans, and investigators said 30% of those plans had policies that preferred biosimilars, 4% of them had non-preferred coverage, meaning originator biologics had to be used first, and 66% covered biosimilars and originators equally, or “on par.”

Biosimilar utilization actually surpassed the use of innovator brands by the first quarter of 2020 (51%), roughly half a year after the beginning of the study period.

Fowler A, Borgert R, Polson M, et al. The emergence of therapeutic oncology biosimilars: payer’s perspective. Presented at: AMCP 2021; April 12-16, 2021. Accessed April 15, 2021. https://amcpannual2021.pathable.co/organizations/AETMfk4CdeFgWTR4v

Study authors measured savings, conversions to biosimilars, and payer policies for 3 originator brands 

Study: Step Therapy Contributes to Biosimilar Utilization 

A New York state Medicaid biosimilar preference initiative was successful in significantly boosting biosimilar use over 2019, according to a poster presentation at AMCP 2021.

For example, from the second to fourth quarters of 2019, the total percent utilization of infliximab (Remicade) biosimilars went from 59% to 78%; filgrastim (Neupogen), 87% to 94%; pegfilgrastim (Neulasta), 70% to 89%, and epoetin alfa (Epogen), 51% to 86%, investigators said.

Although they are as safe and efficacious as originator brands, and often cheaper, biosimilars in New York state cannot be automatically substituted at the pharmacy counter for originators, so provider prescriptions are required for them to be used. It was therefore necessary to bring providers on board with the biosimilar preference plan to get them to help make the conversion to biosimilar use, the investigators said.

The state Medicaid plan launched a concerted effort 6 months prior to launch of the plan to communicate with providers and share information on biosimilar equivalence to reference products. In addition, a pharmacy team reached out to providers to promote the authorization of biosimilar use among plan beneficiaries who were already receiving originator biologics.

According to the poster information provided, use of the 4 originator drugs was at or close to 100% of total utilization prior to the start of the program in the first quarter of 2019. Use of all originator brands dropped below 25% of total utilization by the fourth quarter of 2019. Conversely, biosimilar use for these 4 drug types exceeded 75% of total utilization by the end of that year.

The year-long rise in biosimilar use was steep, not gradual. Biosimilar use as a percent of total utilization exceeded 50% by the second quarter of 2019, investigators said.

“The upward trend in the utilization of the biosimilar vs reference products show that a provider-focused strategy with a phased approach was successful,” the study authors said.

Among the strategies employed to make the biosimilar promotion plan successful were not only provider outreach and communication, but also the establishment of biosimilar preferences in clinical criteria and reconfiguration of the medical and pharmacy benefit. As part of the latter, coding was adjusted to reflect biosimilar preferences and formulary documents and authorization grids were updated.

The outreach effort included communications to 1560 hematologist/oncologists, 378 rheumatologists, 1498 gastroenterologists, 823 nephrologists, and 805 dermatologists. A retrospective claims analysis was used to determine how rapidly the conversion from reference products to biosimilars occurred.

Explaining the desire to switch to lower-cost biologics, such as biosimilars, the authors wrote that although biologics are valuable for treatment of patients with complex and chronic health conditions, “these medicines come with a high cost, creating challenges for both the patient and the payer.”

Huang D, Sikder A, Banbaji F, Felton C, Patel A, Moncayo E. Conversion from the reference product to the biosimilar: experience of a New York state Medicaid plan. Presented at: AMCP 2021; April 12-16, 2021. Accessed April 14, 2021. https://amcpannual2021.pathable.co/organizations/DgLQkoXaW5MohLp7H#/?

New York Medicaid achieved 78% to 94% biosimilar utilization for 4 originator brands during a focused effort in 2019. 

New York Medicaid Ramps Up Biosimilar Use

Based on the success of a biosimilar switching program, Nedzad Pojskic, PhD, MSc, vice president of Pharmacy Benefits Management for Green Shield Canada, detailed why payers should become bigger advocates for biosimilar uptake, at the Festival of Biologics USA meeting.

Canada ranks third in the world in per capita spending on drugs ($1012 vs $1324 in Switzerland and $1457 in the United States), he said, explaining the need for biosimilar savings.

“I think it's really important to recognize that as payers in this country, we have to be explicit around being leaders in educating various stakeholders, whether they be physicians, other sorts of players in the system, patients, or those in leadership roles, to support a viable biosimilar market and to move forward,” said Pojskic.

 have begun executing biosimilars switching initiatives, Pojskic noted that Green Shield Canada was the first payer to have a policy that preferred biosimilars to originators.

Under the program, patients with a number of rheumatic conditions are either started on or switched to biosimilar versions of infliximab, etanercept, and rituximab, whose respective originator brands are Remicade, Enbrel, and Rituxan. Other biosimilar switches are expected with future program expansions.

Pojskic said that, for him, one of the most important lessons to come out of implementing a biosimilar transition program such as this was that payers are the real “gatekeepers” to biosimilar uptake.

“Evidence has shown us time and again that when payers allow open access to an originator and a biosimilar with no preferential policies for biosimilars, the uptake naturally flows to the originators….However, with more aggressive policies that target a sustainable biosimilar market and the uptake of biosimilars in preferential fashion, we start to see payers being a really important part of this equation,” he said.

When biosimilars and originators are treated equally on the formulary, patients and providers flock to originator products because they have historical comfort with using the dominant brands. As a result, biosimilar uptake occurs very slowly, Pojskic said.

So far, Green Shield Canada’s program is a success, generating an average of $8500 in savings per member annually.

Of the patients involved in the program, 55% transitioned to a biosimilar and 14% stayed on the originator but were billed for the price of the biosimilar, which resulted in reduced costs, Pojskic noted.

Pojskic also said that Green Shield Canada made it a priority to work with patients to ensure comfort with biosimilar switching, and this was successful. He reported that patients understood and were receptive to the change, had talked with their physicians about transitioning, and appreciated the support and aid given by nurses.

The Canadian health care system primarily functions as a Medicare-like structure that covers most aspects of hospital and physician care. However, pharmaceuticals are different in that they are funded both privately and publicly. Canada spent $39.8 billion on drugs in 2018, and of that, $12.30 billion and $14.33 billion was privately and publicly funded, respectively, and out-of-pocket costs for pharmaceuticals were $13.10 billion, Pojskic said.

The share of total pharmaceutical costs generated by biologics spending 

 year-over-year, from 20% in 2015 to 24.7% in 2019. Pojskic said that

number to grow as more biologics enter the market.

As biosimilars have entered the market, discounts from originator costs have ranged from 17% for filgrastim biosimilars to 50% for some infliximab biosimilars, he said 

Canada is one of the largest purchasers of originator infliximab, but at the end of 2018, uptake of infliximab biosimilars was only at 8% of total use, slightly above the United States (7%) but significantly trailing Norway (98%), Poland (96%), the United Kingdom (92%), Austria (89%), and Italy (79%), according to Pojskic’s presentation.

everal factors pose barriers to biosimilar uptake in Canada:

There are no interchangeability policies (pharmacists cannot simply substitute biosimilars without physician approval)

Payer policies offer reimbursement for biosimilars without making them preferred products

Switching to biosimilars was not encouraged until recently

Originator manufacturers interfere with biosimilar uptake

Pojskic said a major hurdle that had to be overcome when implementing the biosimilar transition program was addressing the common concern that there is not enough evidence to support the safety of biosimilar switching.

To combat this, Green Shield Canada produced a systematic review of studies showing that switching between originators and biosimilars was safe and effective. The review encompassed 178 studies, of which 140 were based on real world evidence, and included data on 21,000 patients and 10 biologic agents.

“There's plenty of evidence to support biosimilar transitioning and it all points in exactly the same direction. We knew that this evidence was more than enough to safely engage in biosimilar transitioning and to create a program,” said Pojskic.

To overcome provider and patient preferences for brand originators, there has to be more of an incentive to use biosimilars, explains Nedzad Pojskic, PhD, MSc, Green Shield Canada.

Green Shield Canada: Preferential Status Is Vital to Biosimilar Uptake

Providers and health care institutions are going to need a lot more real-world data on how patients respond to various biosimilars and switches between biosimilars and reference products, according to a varied panel of private practice, academic hospital, and group purchasing organization experts in a discussion at the Community Oncology Alliance virtual Community Oncology Conference 2021.

“If we can solve the issue of real-world evidence and data and supply that, I think that will support the use of biosimilars moving forward,” said Sandeep Parsad, PharmD, MBA, BCOP, assistant director of pharmacy at University of Chicago Medicine (UCM).

Providers are going to need convincing, particularly as the choices among biosimilars become more numerous, the panel said. In the oncology space, biosimilars as therapeutic drugs are fairly new, although in supportive care these have been used much longer. And it is often stated that oncologists, especially, become more circumspect in the disease setting about the choice of agents, preferring to go with a well-established originator brand that both they and the patient may have come to trust. To encourage more switching to biosimilars, more evidence is going to be the tool for that, said E. Randolph “Randy” Broun, MD, a blood and marrow transplant specialist with Oncology Hematology Care (OHC), of Cincinnati, Ohio.

“I think data are really lacking in this area. Physicians are going to want data to understand that these truly are biosimilars that are interchangeable and they’re not shortchanging their patients by doing this, even under pressure from payers,” he said.

There’s an important distinction to be made, he said. At his practice, at least, biosimilars are a concept that physicians are very familiar with and they now use these agents in many settings and are comfortable with them. But their confidence in biosimilars can be strained when multiple versions of a single reference product start to appear and they are tasked with making the right choices for their patients.

“Once we have 8 different Herceptins (trastuzumab), are they all the same? Is it reasonable to simply pull a different one off the shelf for a patient who got something different 3 months ago? That will be a barrier, I believe. And you’re only going to solve that with a lot of data that are very convincing that these things are perfectly interchangeable,” Broun said.

Cardinal Health has recognized the value in using biosimilars, as their discounts, particularly when many are available on the market, can be significant, and became proactive with its participating physician practices to cultivate an understanding of these agents that would translate into greater use, according to Sonia T. Oskouei, PharmD, BCMAS, DPLA, vice president of Biosimilars for Cardinal Health.

Parsad said the same goes for her institution. “We took a very purposeful approach to meeting with physicians and nursing staff to talk about the regulatory requirements for approval and demonstrate how biosimilars are similar to reference products, how they have a high standard for safety and quality,” she said.

When it approves a biosimilar, the FDA certifies that it is as safe and effective as the original biologic, and that it has been rigorously evaluated, but the FDA doesn’t give it automatic interchangeable status, meaning pharmacists would be free to substitute the biosimilar with a reference product without informing the physician. Additional requirements are needed for that. It has been hard to explain to physicians that that shouldn’t stop them from prescribing biosimilars, Parsad said. “We felt that was a bit of a bump for us. This is what I’ve heard as well with other colleagues around the country, that physicians do prefer that they are informed when there is a decision whether we should switch or not from the reference product to the biosimilar. But I feel like it went fairly smoothly once there was this very open dialogue.”

It was more of a challenge to develop policies about switching from reference products to biosimilars and in what instances this should occur, she said. A lot of issues arose, such as whether patients should be asked for fresh consent before they are prescribed a biosimilar after having been on a reference product, and if a patient’s condition is stable on a reference product, is it really wise to “rock the boat” and prescribe a biosimilar? And further, following a new diagnosis of metastatic disease, should patients be started on a biosimilar instead of the reference product?

“We had to really work through this saying this is something that we believe as an organization. We believe in the literature, we believe in the data, and we would like to move forward. So, we’ve gotten past that hump,” Parsad said. 

All that said, UCM still wants to see more real-world evidence that shows biosimilars can stand the test of time outside of clinical trials performed in limited numbers of patients for the purposes of FDA approval, she said.

Oskouei agreed. “The conversation has definitely evolved with a desire for more real world evidence and studies around biosimilar to biosimilar switching. With 5 trastuzumab biosimilars on the market now for example, and more in the pipeline, this dynamic is becoming something that providers must navigate.”

At OHC, providers are now using biosimilars in practically 100% of situations when it comes to trastuzumab, rituximab, and supportive care products, such as growth factors for the control of neutropenia in patients treated with chemotherapy products, Broun said. But the practice has found it more manageable to administer a single brand of biosimilar overall except in instances where payers demand something different. “Actually, the ones that give us the most trouble as far as the payers are concerned are the growth factors. Every insurance company seems to have their favorite [pegfilgrastim], and so we stock 3 or 4 of those and we have to sort of interchange them.” 

It would be nice if payers were more lenient about the choice of biosimilars, panelists said. For example, Parsad noted that the administrative work that goes into payer authorizations could be used on something more beneficial, such as patient education and support. “We’re dealing with it as best we can, but it’s unfortunate,” she said.

These issues resemble growing pains for a relatively new option in medicine that is already proving its value, said Kathy Oubre, MS, CEO of Pontchartrain Cancer Center in Louisiana, who served as panel moderator. “The US market is still in its infancy. We just need to let it mature. Biosimilars have been, at least for our organization, a great way to help provide some cost savings to the system and to the patient.”

Community Oncology Alliance

Next-stage biosimlar acceptance will stand on the strength and availability of real-world data as more of these biologics are launched, a Community Oncology Alliance (COA) conference panel said.

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