Tony Hagen is senior managing editor for The Center for Biosimilars

Tony Hagen

The Oncology Care Model (OCM), begun in 2016 by CMS to promote value-based care over costly “buy and bill” pharmacy practices, has “led to reduced use of some high-cost supportive care medications, with patterns suggesting more value-conscious care,” according to findings presented at ASCO 2021.

Alternative payment models have potential to drive value-based changes in medication use during cancer care.

Investigators sourced Medicare claims from 2013 to 2019 in an evaluation of outpatient supportive care medication use during chemotherapy treatment at practices participating in the OCM or in “propensity-matched comparison practices,” used as an artificial cohort.

Except for a filgrastim biosimilar analysis, where the adoption trend was assessed, the investigators used a differences-in-differences (DID) statistical method to compare findings between cohorts.

The OCM had no effect on the use of any type of bone supportive medication (denosumab or bisphosphonate) among patients with metastasized bone cancer; however, it did result in lower use of denosumab in patients with breast cancer (DID = –5.0 percentage points; 90% CI, –7.1 to –2.8), prostate cancer (DID = –4.0 percentage points; 90% CI, –5.9 to –2.2), and lung cancer (DID = –4.1 percentage points; 90% CI, –7.4 to –0.9).

The OCM resulted in lower use of neurokinin-1 (NK1) antagonists and serotonin antagonists in patients who were starting chemotherapy with high or moderate emetic risk, according to the authors. This included a 6-percentage-point reduction in use of NK1 antagonists for patients undergoing high–emetic risk chemotherapy (90% CI, –9.0 to –3.1), as opposed to no effect on antiemetic use during low–emetic risk chemotherapy.

No change was noted in use of prophylactic white blood cell growth factors among patients receiving chemotherapy with high risk for febrile neutropenia (FN).

A 7.6-percentage-point reduction in prophylactic granulocyte colony stimulating factor (G-CSF) was observed for patients with breast cancer receiving chemotherapy with intermediate risk for FN (90% CI, –12.6 to –2.7). Conversely, no change in prophylactic G-CSF use was observed for patients with lung or colorectal cancer.

The OCM resulted in faster adoption of filgrastim biosimilar vs originator product for patients treated with this agent (differential trend estimate, 2.6%; 90% CI, 1.0%-4.4%).

“Alternative payment models have potential to drive value-based changes in medication use during cancer care,” the authors concluded.

Brooks GA, Landrum MB, Kapadia NS, et al. Impact of the Oncology Care Model on use of bone supportive medications, antiemetics, and growth factors. Presented at: ASCO 2021: June 3-7, 2021. Abstract 1517. 

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Investigators noted a reduction in use of high-cost supportive care agents, suggesting that the value-based Oncology Care Model (OCM) is working. 

Study: OCM Reduces Use of Some Supportive Care Medications and Boosts Filgrastim Biosimilar Use

Investigators in Alberta, Canada, said no significant differences in pathologic complete response rates (pCRs) were observed in a study of patients with human epidermal growth factor receptor 2–positive (HER2+) treated with the biosimilar trastuzumab Ogivri vs the originator product, Herceptin.

pCR rates were similar for patients treated with [Ogivri] compared with [Herceptin] in our real-world study of HER2+ neoadjuvant [early breast cancer] and comparable to pivotal phase 3 trials.

The study authors postulated that although biosimilars are certified as having no clinically meaningful differences from originator products, there is potential for clinically meaningful differences in outcomes because biosimilar manufacturers must produce new cell lines to replicate originator biologics and are not given access to the originator cell lines.

Concerns about “this inherent alteration in production” are settled through phase 1 pharmacokinetic and pharmacodynamic comparative studies and phase 3 studies to demonstrate biosimilar equivalency in patients for at least 1 indication of the originator product, investigators said.

Prior confirmatory studies have evaluated the biosimilarity of Ogivri and Herceptin in the metastatic HER2+ setting. In this study, investigators sought to elucidate biosimilar equivalence in the neoadjuvant, or early breast cancer (EBC), setting.

The study enrolled patients (N = 136; 56% originator, 43% biosimilar) treated with trastuzumab originator from November 2018 to October 2019 and the biosimilar from December 2019 to September 2020. There was no crossover between products. Investigators used logistic regression to control for factors that might affect pCR in either cohort, such as biosimilar or originator agent, age, tumor type, node positivity, tumor grade, hormone receptor status, treatment with chemotherapy, and whether chemotherapy treatment was completed.

Based on the logistic regression model, investigators saw no significant difference in pCR odds for patients treated with biosimilar vs originator (odds ratio [OR], 1.1; 95% CI, 0.5-2.4; 

 = .85). However, there was a statistically insignificant lower likelihood of pCR in patients with anthracycline use (OR, 0.72; 95% CI, 0.3-1.6; 

Investigators observed no significant differences in baseline characteristics among patients except the proportion of those with node negative results: 39%, biosimilar; 14.3%, originator (

 = .001). For patients treated with biosimilar vs originator, pCR was a nonstatistically significant 35.6% vs 40.3%, respectively (

“pCR rates were similar for patients treated with [Ogivri] compared with [Herceptin] in our real-world study of HER2+ neoadjuvant EBC and comparable to pivotal phase 3 trials,” the authors concluded.

Yang C, Khwaja R, King K, et al. Trastuzumab-dkst versus trastuzumab: real-world pCR rates in patients with HER2+ breast cancer treated with neoadjuvant chemotherapy plus trastuzumab from Alberta, Canada. Presented at: ASCO 2021; June 3-7, 2021. Abstract e12569.

Investigators further elucidate the equivalence of a trastuzumab biosimilar vs Herceptin in human epidermal growth factor receptor 2–positive (HER2+) breast cancer. 

Ogivri Equivalence Demonstrated in Neoadjuvant HER2+ Comparative Trial

Eleven biosimilars for use in oncology have been launched since the start of 2019, and investigators who sought to measure oncologists’ response to these agents reported initial hesitation, followed by robust uptake and hefty savings.

They noted that the biosimilar competition had little effect on reference product prices, which “remained stable.”

We conclude that uptake of biosimilars among oncology providers between 2019-2020 was rapid, although the extent of biosimilar prescribing varied among products. Biosimilars offered greatly reduced costs to providers, although reference product prices remained stable despite increased biosimilar competition.

The findings were reported in an abstract published at the ASCO 2021 meeting. Investigators drew their data from prescription information published by Wolters Kluwer (n = 130,836), sales data from IQVIA, and dosage information published by ION Solutions.

Investigators found that in 2020, 8.2% of new prescriptions for bevacizumab, rituximab, and trastuzumab were for biosimilar versions. For bevacizumab, there are currently 2 biosimilars available; rituximab, 3; and trastuzumab, 5.

Findings for use of trastuzumab biosimilars revealed a dramatic increase from the first year of availability to the next. In the first 3 months of 2019, 7.3% of initiating first-line patients were prescribed trastuzumab biosimilar vs reference product. In the first quarter of 2020, when all 5 trastuzumab biosimilars had become available, the new prescriptions rate was 80.5% for patients receiving first-line care.

Uptake rates differed for individual biosimilars. The investigators reported that Ruxience, the first available rituximab biosimilar, had initial uptake of just 2.3%.

And further, they did observe willingness among oncologists to switch patients from reference products to biosimilars. They said 11.1% of patients (bevacizumab, 11.3%; trastuzumab, 14.1%; rituximab, 7.9%) were transitioned from the reference biologics to biosimilars during treatment.

“Uptake was particularly rapid for trastuzumab biosimilars,” investigators said. “Among patients on trastuzumab at the time of its first biosimilar launch, 18.2% switched to [the Kanjinti trastuzumab biosimilar] in the first 90 days postlaunch.”

Significant savings were a feature of the use of biosimilars in the oncology practices, the authors said. Costs per biosimilar prescription were lower than the reference product prescription cost by 42.0%, 29.9%, and 89.5% for trastuzumab, rituximab, and bevacizumab, respectively.

“However, biosimilar launches had little impact on reference product pricing, with 2019 to 2020 year-over-year (YOY) differences in price per prescription close to the YOY averages in previous years (2015-2019) for all 3 reference products,” the authors wrote.

McGlynn KA, McGarry J, Patel KB, Clinton N. Real-world trends in biosimilar prescribing among oncology providers, 2019-2021. Presented at: ASCO 2021: June 3-7, 2021. Abstract e18701.

When biosimilars emerged in oncology, oncologists dipped in a toe and then got serious, according to a retrospective study on usage and savings presented at ASCO 2021.

Study Suggests Oncologists' Use of Biosimilars Grew From Trickle to Flood

An experiment with automatic prescribing of biosimilars at Texas Oncology resulted in a dramatic savings and increase in biosimilar vs originator usage rates, investigators reported at ASCO 2021.

Texas Oncology is a network of approximately 460 physicians and oncologists who serve patients with cancer in rural and urban communities throughout Texas. 

A central pharmacy team reviewed all prescriptions and substituted biosimilars for originator biologics, unless payers insisted otherwise or the relevant biosimilar was not in the practice formulary. Texas Oncology also compiled a weekly report identifying all patients who would benefit from switching to biosimilars, and substitutions were then made. In collaboration with McKesson Specialty Health, patient and clinician education was incorporated into the biosimilar usage effort to improve results.

Texas Oncology began the substitution in July 2020 with rituximab and followed up in September 2020 and October 2020 with bevacizumab and trastuzumab substitutions, respectively. By December 2020, utilization of biosimilars rose to 80% from 5% for rituximab, 88% from 9% for bevacizumab, and 74% from 8% for trastuzumab.

Investigators calculated the potential savings per administration at $550 for bevacizumab, $850 for trastuzumab, and $1400 for rituximab. “In 1 month alone, this project dramatically reduced cost by $4 million or 21% by conversion to these 3 biosimilars,” they wrote.

The investigators also predicted that additional savings would be possible by using multidose vials of biosimilar product rather than single-dose vials.

“Our comprehensive team approach successfully deploys therapeutic interchange of biosimilars for brand drugs in a community oncology practice which leads to substantial cost savings. This has real implications in controlling the total cost of care,” the authors of the study wrote.

Wilfong L, Dave N, Garey JS, et al. A successful model of biosimilar adoption in a community oncology practice. Presented at: ASCO 2021: June 3-7, 2021. Abstract 6514.

The substitution program was carried out in 2020 and yielded savings of $4 million in 1 month, investigators reported at ASCO 2021. 

Texas Oncology Reports Savings From Biosimilar Substitution Effort

for the biosimilars and women’s health products company Organon, which was formed as a spinoff from Merck.

Organon is based in Jersey City, New Jersey, and has a portfolio of more than 60 medicines and therapeutic products. The company will start life with an estimated $6.5 billion in annual revenue, 80% of that derived from sales outside the United States.

Organon will not be involved in the research side of drug development. Rather, it aims to partner with research and development innovators in bringing their products to market, Organon Chief Financial Officer Matt Walsh told 

. “For smaller, more agile, faster-moving innovators, they see a company like ours as the ideal partner because we’re not developing [drugs] ourselves,” he said.

The company’s core business is in contraceptives and fertility products for women, supplemented by other women’s health products and Merck’s former biosimilars portfolio. The company will market infliximab (Renflexis), etanercept (Brenzys, Eticovo), bevacizumab (Aybintio), trastuzumab (Ontruzant) and adalimumab (Hadlima) 

in partnership with Samsung Bioepis of the Republic of Korea.

Other products include dermatology, pain, respiratory, and cardiovascular treatments.

Lupin Files Application for Pegfilgrastim Biosimilar

Mumbai, India-based Lupin said the FDA has accepted its biologics license application for a pegfilgrastim biosimilar candidate referencing Amgen’s Neulasta. The company said the product would target an estimated $3.66 billion market for pegfilgrastim in the United States.

“The pegfilgrastim filing is our first biosimilar filing in the United States and is a milestone in our research and innovation journey,” said Nilesh Gupta, managing director.

Lupin develops and markets branded and generic medicines and biotechnology products in the United States, India, South Africa, the Asia Pacific region, Latin America, Europe, and the Middle East. Those include cardiovascular, antidiabetic, respiratory, anti-infective, gastrointestinal, central nervous system, and women’s health therapeutics. The company states that it is the third largest in the United States by prescriptions sold and maintains a Baltimore, Maryland, office.

Positive Results for Tocilizumab Candidate

 from a phase 3 study of a proposed biosimilar tocilizumab (BAT1806), referencing Actemra. “The comparative study met its primary end points and showed equivalent efficacy and [a] comparable safety profile in patients with moderate-to-severe rheumatoid arthritis [RA] inadequately controlled by methotrexate therapy,” they said.

The originator tocilizumab brand is indicated for moderate-to-severe RA in adults, juvenile idiopathic polyarthritis, systemic juvenile idiopathic arthritis, giant cell arteritis, and cytokine release syndrome. The primary end point in the study was American College of Rheumatology 20% response criteria.

For Bio-Thera, based in Guangzhou, China, BAT1806 is the third proposed biosimilar the company has developed that has achieved positive phase 3 results. “These results demonstrate the potential of our proposed tocilizumab biosimilar to be a safe and effective treatment,” said Shengfeng Li, PhD, CEO at Bio-Thera.

“We are excited about these results and believe BAT1806 demonstrates equivalence in safety and pharmacokinetics as well as a comparable safety and immunogenicity profile to the reference product,” said Ian Henshaw, head of Global Biosimilars at Biogen, which is based in Cambridge, Massachusetts, and would handle marketing and manufacture of the product in all counties outside of the China area.

Organon will do marketing but not research and development, Biogen and Bio-Thera move forward with tocilizumab candidate, and Lupin promotes a pegfilgrastim biosimilar.

News Roundup: Organon Starts Life as a Biosimilars Marketer

Investigators have reported a rare incidence of immunogenicity “with possible clinical and biological consequences” for patients treated with biosimilar rituximab (Riximyo, GP2013).

Investigators at the Rheumatology Department of Cochin Hospital, Paris, France, enrolled 159 patients who were treated with GP2013 (Riximyo; Sandoz) since March 2018 and included those who were previously treated with originator rituximab (RTX). The biosimilar is marketed in Canada and the European Union, but not in the United States. 

The immunogenicity of patients treated with rituximab is a rare event with possible clinical and biological consequences, especially in patients with high antibody levels.

Patients had rheumatoid arthritis (RA; n = 108), systemic sclerosis (SSc; n = 16), mixed connective tissue disease (MCTD; n = 15), and various other conditions in smaller proportions. The investigators said 25% of patients overall were RTX naive, and 75% were in maintenance therapy with RTX prior to switching to the biosimilar in March 2018.

Patients were tested for antidrug antibodies (ADAs) and residual rituximab concentrations. In the initial analysis, prior to the second GP2013 infusion, findings showed 8 patients (5%) positive for antidrug antibodies (RA, 5; MCTD, 1; SSc, 1; systemic lupus erythematosus [SLE], 1).

ADA rates were from 6 to greater than 100 ng/mL and “were associated with undetectable residual rituximab concentrations.” Among the 8 patients positive for ADAs, 6 had previously received RTX and 2 were RTX naive.

Investigators reported a trend toward higher mean (SD) body mass index for patients testing positive for ADAs (28 [7] vs 25 [6] kg/m

 = .12). They reported no associations between RTX immunization and age, disease duration, combination with conventional disease-modifying antirheumatic drugs, mean interval between infusions, or cumulative originator rituximab dose.

In stratification, the investigators reported 3 patients with high ADA levels (≥100 ng/mL), including 2 with RA and 1 with MCTD; decreased efficacy for 2 patients; incomplete B-cell depletion; RTX dose escalation from 500 mg to 1 g; and 1 severe allergic reaction.

Among 5 patients with mild ADA levels (6-22 ng/mL), the investigators reported 3 with RA, 1 with SLE, and 1 with SSc. Treatment was continued in all 5 cases with no loss of efficacy within an average of 13 months of follow-up. One minor allergic reaction was reported.

“The immunogenicity of patients treated with rituximab is a rare event with possible clinical and biological consequences, especially in patients with high antibody levels,” the investigators concluded.

Avouac J, Cougnaud Murail R, Goulvestre C, et al. Immunogenicity of rituximab biosimilar GP2013: a rare event, but not without consequences… Presented at: EULAR 2021; June 2-5, 2021. Poster 0600.

Immunogenicity was rare but concerning for patients who switched from originator rituximab to the biosimilar Riximyo, investigators reported. 

French Investigators Report Rituximab Immunogenicity Findings

Real-world findings for 2 Samsung Bioepis biosimilars were presented at EULAR 2021 and offered support for clinicians' use of these products in place of originator agents.  

A real-world analysis has demonstrated that patients with ankylosing spondylitis (axSpA) or rheumatoid arthritis (RA) can be initiated on the infliximab biosimilar SB2 (Flixabi) and patients with axSpA, RA, or psoriatic arthritis (PsA) can be switched to SB2 from the reference product without loss of disease control or dose penalty over the 12-month, post-initiation or transition period.

“Over 56% of SB2-naïve patients and over 79% of patients transitioned from the reference product remained on SB2 at 12 months following initiation,” investigators reported at EULAR 2021. The results were from the PERFUSE study, an ongoing, noninterventional study of patients with rheumatology (n = 496) and gastroenterology (n = 737) conditions receiving infliximab as routine therapy.

PERFUSE was initiated to provide understanding of long-term outcomes in patients who were started on SB2 in the real-world setting. Dosage, disease activity, and persistence on SB2 over time and up to 24 months after initiation were end points.

Investigators aim to continue the study to 24 months post initiation of SB2.

A real-world study of patients with autoimmune diseases demonstrated equivalence between adalimumab reference product and the biosimilar SB5 (Hadlima).

Investigators enrolled patients with RA, axSpA, PsA, ulcerative colitis, and Crohn disease who were initiated on SB5 following a minimum 16 weeks of treatment with the originator product (Humira). The study was conducted at clinics in Belgium, Germany, Ireland, Italy, Spain, and the United Kingdom.

Investigators sourced retrospective clinical data on patients (N = 504) for the 24 weeks prior to transition to SB5 and prospective or retrospective data for the 48 weeks following transition. Primary outcomes were baseline clinical characteristics, disease activity, and clinical management over time.

Authors of the study said for most patients there was no meaningful difference in disease score or dose regimen of SB5 by week 48 after transition to the biosimilar. Follow-up will continue until the fourth quarter of 2021.

“This investigative analysis provides a first insight into clinical management of patients over 48 weeks, in a contemporary cohort of European Union patients with established RA, axSpA, and PsA, switched from reference product to SB5 in clinical practice,” they wrote.

1. Fautrel B, Bouhnik Y, Dougados M, Freudensprung U, Addison J. PERFUSE: a French prospective/retrospective noninterventional cohort study of infliximab-naïve and transitioned patients receiving infliximab biosimilar SB2; 12-month analysis. Presented at: EULAR 2021; June 2-5, 2021. Poster 0614.

2. Müller-Ladner U, Gaffney K, Jadon D, Freudensprung U, Addison J. The PROPER study: interim analysis of a pan-EU real world study of SB5 biosimilar following transition from reference adalimumab in patients with rheumatoid arthritis, axial spondyloarthritis or psoriatic arthritis. Presented at: EULAR 2021; June 2-5, 2021. Abstract 0204.

Real-world clinical data compiled for patients with autoimmune disorders were presented at EULAR 2021.

Poster Roundup: Results Presented for Samsung Bioepis Biosimilars for Adalimumab, Infliximab

With its sights set on launching a high-concentration, citrate-free formulation of adalimumab in the European Union this year, Celltrion Healthcare presented positive 1-year results confirming equivalence of the biosimilar (CT-P17, Yuflyma) in patients with rheumatoid arthritis (RA) at EULAR 2021.

Celltrion hopes to gain a share of the lucrative market for high-concentration, citrate-free adalimumab (Humira; AbbVie), which has been displacing sales of lower-concentration adalimumab since 

. The Incheon, Republic of Korea, company would be the first to launch a biosimilar formulation of the high-concentration 100-mg/mL adalimumab product.

“We anticipate launching Yuflyma in 7 European countries, including Germany and France, in the third quarter of 2021 and in 3 additional European countries, including Italy, in the fourth quarter,” Celltrion told The Center for Biosimilars

No date for a US launch has been established so far; however, access to the US market is tightly controlled by the originator company’s extensive patent portfolio on adalimumab, and lower-concentration formulations are not expected to debut in the United States until 2023.

The randomized, double-blind, phase 3 trial for Yuflyma presented at EULAR, the annual European Congress of Rheumatology, met primary and secondary end points for efficacy, pharmacokinetics, safety, and immunogenicity, demonstrating outcomes comparable to reference adalimumab in patients (N = 648) with moderate to severe RA despite methotrexate treatment.

Patients were randomized 1:1 to receive a 40-mg dose of the biosimilar or reference adalimumab every 2 weeks through week 24. At week 26, patients were randomized again to treatment maintenance on the biosimilar (n = 303) or reference product (n = 153), or a switch from reference adalimumab to Yuflyma (n = 151). This round of treatment continued through week 48.

Demonstration of equivalent efficacy and comparable safety of CT-P17 to EU-sourced adalimumab in this study supports the ongoing clinical evaluation of CT-P17 as an adalimumab biosimilar.

For patients receiving maintenance therapy and those switched from reference adalimumab to Yuflyma up to week 52, the investigators reported comparable efficacy in terms of American College of Rheumatology–defined response rates for reduction in joint swelling and tenderness.

Similarly, drug concentrations at the lowest point prior to redosing (C

) also were comparable in all 3 treatment groups. Observed mean C

 levels fell within parameters reported for reference adalimumab (5-8 mcg/mL).

Safety profiles for patients receiving Yuflyma also were comparable. The most common treatment-emergent adverse event (TEAE) was neutropenia. Injection site reactions, hypersensitivity/allergic reactions, and infections also were similar to established TEAEs for reference adalimumab.

The investigators said antidrug antibody (ADA) and neutralising antibody (NAb) results also were equivalent among patient cohorts. ADA/Nabs were 28.4%/24.8%, 27.0%/24.3%, and 28.3%/26.3% in patients maintained on Yuflyma or reference adalimumab or switched to Yuflyma, respectively.

“Demonstration of equivalent efficacy and comparable safety of CT-P17 to EU-sourced adalimumab in this study supports the ongoing clinical evaluation of CT-P17 as an adalimumab biosimilar,” said Jonathan Kay, MD, a professor at the University of Massachusetts Medical School and the trial's principal investigator. 

In tandem with the trial results presentation, Celltrion stated that the European Commission has granted marketing authorization for the company’s infliximab biosimilar (Remsima) for use without intravenous (IV) infusion for new and existing patients with RA. Remsima received a positive recommendation for approval from the European Medicines Agency (EMA) as subcutaneous therapy without IV loading in adults with RA in March 2021.

Alvotech, a Reykjavik, Iceland–based company, also has developed a 100-mg/mL low-volume formulation of adalimumab (AVT02) but is facing legal action from AbbVie, which has made patent infringement 

 on its AVT02 marketing applications in September 2021 and late 2021, respectively. Alvotech has responded to the AbbVie litigation with a 

 seeking to invalidate Humira patents the company says are unjustified.

Celltrion announces the launch timing for its much anticipated high-concentration formulation of adalimumab and presents trial data supporting equivalence to the reference product.

Celltrion Supports High-Concentration Adalimumab Biosimilar Launch With Phase 3 Trial Data

It is often said that legislators and patient advocates hope the biosimilars market will evolve as successfully as the generic market has, providing for robust competition and price declines that improve access. But a drug industry expert who spoke at the Association for Accessible Medicines' Access! meeting said generic and specialty drug markets, which include biosimilars, are evolving in very different ways.

The high costs of specialty drugs have caused payers and pharmacy benefit managers (PBMs) to develop distribution systems that afford high levels of control over patient behavior and access to these medications. “The PBMs will say to their plan sponsors—the insurers—‘Hey, if you limit the number of specialty pharmacies, limit the number of entities that can dispense this, we can keep an eye on the patient, make sure they’re doing the right thing,’” said Adam Fein, PhD, CEO of the Drug Channels Institute.

“One of the risks they have is a bad policy coming through, not because there’s some sort of bad intent but because there’s just a lack of understanding of what’s happening. 

As a result, manufacturers may end up launching their specialty drugs into limited networks of specialty pharmacies, typically mail order pharmacies, as opposed to the tens of thousands of retail pharmacies that might be involved in the distribution of generic brands.

Another issue affecting distribution of biosimilars is the dependence on rebates, which manufacturers offer as incentives for use of their product over 1 or more rivals. Narrow specialty drug networks and rebates are going to present unique challenges for biosimilar competition over the next few years as the number of biosimilars increases, Fein said.

“There’s a battle for control of the specialty patient," he said. "Biosimilar manufacturers are going to be dealing with payers who now control the dispensing and distribution channels for specialty drugs on the pharmacy side, and that’s going to create a challenge."

Biosimilars are certified by the FDA to be as safe and efficacious as their originator biologics. Once biosimilars start being approved as interchangeable to originators, meaning substitutable for originators without physician approval, the issue of access will become more complex, Fein said.

He cited the example of the 6 FDA-approved adalimumab (Humira) biosimilars scheduled to launch in 2023 in the United States. “One, and possibly 2, of these Humira biosimilars may be interchangeable for specific indications. It’s not clear what that’s going to mean and how the payers are going to play that game, how companies will come to market, how they’re going to price their products, and how the PBMs are going to maximize their own profits to save money for their clients,” he said.

“It’s really going to be a very exciting time for the study of biosimilars and probably a very challenging time if you’re living it,” Fein told the Access! audience, which included a contingent of generic and biosimilar company executives.

There will also be what Fein described as “public policy risk,” because the pace and complexity of the specialty drug market is often far ahead of the working understanding that legislators have, based on his experience. “One of the risks is a bad policy coming through, not because there’s some sort of bad intent but because there’s just a lack of understanding of what’s happening. So, I see that as potentially very problematic for this industry and, frankly, most parts of the pharmaceutical industry and pharmaceutical channel.”

We've reached peak generic penetration. If my math is correct, we’re not going to grow by another 50 percentage points.

If the evolution on the biosimilar side is hazy, so is what has happened on the generic side. Fein said that 5 years ago he could not have predicted the extreme “vertical” consolidation in the pharmaceutical industry or how this would have affected the management of generic drug distribution.

Mergers among industry titans have completely reshaped the way business is done, he said. “These companies are not just horizontally consolidating, with one company buying another company like it. We’ve now seen a dramatic trend toward vertical consolidation. The largest PBMs have integrated with the largest health insurers, which have also become merged with the largest specialty pharmacies and, in many cases, are moving into providing health care services.”

This means that at any level in one of these pharmaceutical totem poles, an entity cannot focus, as before, on maximizing its own profits but must consider the needs of the other members in the chain.

“There’s not a lot of consolidation left to go. There’ll be a few more deals, but we’re getting to a point where it’s going to be hard to consolidate this much further,“ Fein predicted.

Another important consideration is that generics now represent 90% of prescriptions filled, up from 40% 20 years ago, Fein said. He called this state of affairs “peak generic penetration. If my math is correct, we’re not going to grow by another 50 percentage points.”

Government has become the largest payer of all. “More than 40% of all prescriptions in 2019 were paid by Medicare or Medicaid or another government program. This will grow with the aging population. Medicaid expanded enrollment during the pandemic by about 10% to 12%,” Fein said.

Many commercial entities are responsible for the management of government payer programs, and the implication is that their influence will shape these programs, he said. “These are the companies that are controlling access to pharmaceuticals, that are controlling benefit designs that are essentially part of the system. So, keep in mind that if the government does extend its role in health care, you can be pretty sure [this activity] is going to be mediated by the companies that are already the significant contractors for the government in managing health care and, particularly, prescription drugs and generics and biosimilars.”

On the generics side, with peak consolidation, there will be a diminishing number of ways to eke out a profit, to achieve efficiencies that improve margins, Fein said. “The pharmacies will have to work harder and harder to make money dispensing prescriptions. That’s not just a reimbursement challenge. That’s simply an issue of there are only so many dollars they can make when the prescription is $20 or $30.”

A key development amid these industry changes is a snowballing trend toward the use of discount drug cards, such as GoodRx provides. Owing to the rise of generics and the government’s encouragement of generic competition, there has been steep deflation in the cost of small molecule drugs, such that costs of these drugs for many families may never reach coverage thresholds (beyond out-of-pocket costs), whether government or commercial. The average family deductible is $4500, Fein said.

Some consumers may find that they can obtain drugs for less using discount cards than if they rely on their insurance plans, Fein said. This is what's driving even covered consumers to flock to these discount cards. 

Increasingly, health care consumers are using discount cards rather than their health plan coverage for prescriptions, whether it has a prescription benefit or not. That means families and companies are sometimes paying premiums for prescription coverage needlessly. Fein said 36% of people who have commercial insurance use GoodRx instead, and this doesn’t include the many other discount card services available.

In 2016, the retail value of prescriptions GoodRx handled was $700 million in terms of consumer out-of-pocket costs, and that has grown so that this year it will be around $4.5 billion out of pocket, Fein said.

Biosimilar manufacturers may encounter roadblocks in the months and years ahead, and generics manufacturers will find they've hit a ceiling, according to Adam Fein, PhD, CEO of the Drug Channels Institute.

Pharmacy Economist Describes Fork in the Road for Generics and Biosimilars

More education about the value of biosimilars for doctors, nurses, and especially patients could help significantly with getting more of these agents into circulation and achieving savings that, in turn, could be plowed into health care system improvements. This observation came from a recent Medicines for Europe expert panel discussion on biosimilar use in Europe.

“Whenever I speak about biosimilars, the prior knowledge of patients makes them believe that I’m giving them something cheaper that is not the same quality, and they will look at me in a way that says, ‘Are you certain you really want to give me that stuff?’” said Matti Aapro, MD, president of the European Cancer Organization. “I think education is extremely important.”

The news about the pharmacovigilance is that there is ‘no news,’ or nothing [untoward] has happened. 

The panelists suggested moving education about biosimilars into early training for health care professionals, such as doctors and nurses, many of whom can influence how patients perceive biosimilars.

“As we know in biosimilars, the switching process is very important for patients to take biosimilars up, because we sometimes see the nocebo effect with patients and they go back to the innovator product, and this could be prevented if you educate your patients the right way, and it’s not just the nurse’s job. It’s about aligning every health care professional to make this happen,” said Johan De Munter, president of the European Oncology Nursing Society and assistant nurse manager in the University Hospital Ghent Cancer Center, Belgium.

Digestive Cancers Europe (DiCE) has done extensive project work to promote the use of biosimilars in colorectal and gastric cancers, and these efforts have involved participation from pharmacy, clinical, industry, and nursing, said Zorana Maravic, acting DiCE CEO. She’s observed  that patients become more supportive of biosimilar use if you let them know that the savings from these often lower-cost agents can be spent to broaden and improve their care and care facilities.

There should be a setting of health care system priorities that says if the drugs are equivalent, you use the cheapest one.

“If you say to a patient a biosimilar saves money for the health care system, this doesn’t mean anything to them; but if you say biosimilars save money and, in turn, facilities can be improved or patients will have an additional nurse or support from a nutritionist or psychologist, this is something tangible for them,” Maravic said.

She recalled an educational meeting with a group of patients that transformed their attitudes toward these agents. “That was really a magical experience, because we were in a room together with 8 or 9 patients, and we organized the session during an afternoon where, I have to say, patients in the beginning were skeptical about biosimilars because, you know, ‘They’re similar but not equal.’

“That was their perception, and then the experts presented the science and the safety and the role of the European Medicines Agency [in approving biosimilars]. And all that information really changed their perspective, and those 8 or 9 patients are now really advocates for biosimilars,” she said.

Europe is ahead of the United States in biosimilar use and has closely studied the pharmacologic effects of biosimilars. European regulators have made good use of this growing body of evidence to help convince a skeptical public that biosimilars as safe and efficacious as their reference products, said Maja Sercic, policy and science manager for Medicines for Europe.

“The news about the pharmacovigilance is that there is ‘no news,’ or nothing [untoward] has happened. So, I think this is such an important piece of information, that biosimilars are actually safe and there were no complications in the last 15 years. So, regulators share this clinical experience. I think that is really the key, and I think it can really comfort the whole community,” Sercic said.

A big theme with the panel was the existing inefficiencies in health care, which they said are quite large in some instances and in serious need of attention. “We think it’s really important to look at the health care budgets overall. Too often—for us and for everybody—it’s difficult to find the data. We don’t know how the money is invested in every hospital, according to the outcomes that happen, so there are a lot of inefficiencies, and it’s important to stop wasting the money,” Maravic said. “I think that biosimilars can contribute to, if not making some surpluses, definitely in decreasing the budget deficit.”

Waste may involve inefficiencies at the practice level, such as preparing drug for patients who do not show up for their appointments, Aapro said.

The savings from biosimilars can be deployed strategically to cut down on overall requirements for care, Maravic said. “Currently we have a budget for prevention, we have a budget for treatment, and we can use the savings from biosimilars and deploy this into screening. We could save money because a lot of cancers would be detected at an earlier stage.”

It costs $4881 on average to treat a patient with stage I colorectal cancer, whereas stage IV disease requires treatment that costs $48,800. Currently just 14% of the population in the European Union has access to screening, and this just shows the value of earlier screening, Maravic said.

Adding to this, Sercic said that optimal use of biosimilars for just 3 molecules routinely used in cancer could save up to $2.9 billion in Europe. “I think that’s a huge value. And I’m not sure if my perception personally is that not everyone is aware how great the potential actually is.”

The panelists suggested a range of core objectives that, if implemented, would get biosimilars used more often and foster trickle-down savings and health care quality improvements:

“There should be no discussion. There should be a setting of health care system priorities that says if the drugs are equivalent, you use the cheapest one,” Aapro said.

“We should reinvest the biosimilar savings locally in a transparent and tangible way, because then everybody would be able to recognize the value of biosimilars,” Maravic said. 

“Experience and best practices among member states will need to be shared. It’s important to translate that experience into the different country settings. And the European Commission can serve as a platform for doing so,” Sercic said.

“Competition is something that has to be sustainable over the long term, so we need to make sure that we will always have a couple of players in the market to make sure this competition takes place,” she added.

More transparency in how health care money is spent could improve utilization and efficiency, panelists said at the Medicines for Europe event.