Tony Hagen is senior managing editor for The Center for Biosimilars

Tony Hagen

Zydus Cadila, an Ahmedabad, India–based pharmaceutical company, said it has launched the world’s first biosimilar form of trastuzumab emtansine, an antibody drug conjugate that not only counteracts cancer cell growth (trastuzumab) but also delivers a cytotoxic agent to the cancer cell and helps to destroy it.

Zydus Cadila said the biosimilar (Ujvira) will be available on the Indian market and can be of value in treating human epidermal growth factor receptor 2 (HER2)-positive breast cancer, which is highly aggressive and constitutes 20% to 25% of all breast cancers.

“We hope that with this innovation, patients will be able to adhere to the treatment and stand to benefit from the advanced technology without worrying about the cost of the treatment,” said Sharvil Patel, managing director of Cadila Healthcare, in a 

. An estimated 1 in 29 women in India are at risk of developing breast cancer.

In some forms of breast cancer, HER2 receptors are overexpressed on the cancer cell. These receptors receive signals that stimulate the cell to grow and multiply. Trastuzumab attaches to the receptors and blocks the signaling process, causing growth of the cancer cells to stop. Trastuzumab can also alert the immune system to destroy cancer cells.

When trastuzumab attaches to the HER2 receptor, emtansine is able to enter the cancer cell and kill it. The originator trastuzumab emtansine (Kadcycla) was developed by Genentech, a subsidiary of Roche. Zydus Cadila said it would market the biosimilar version “at nearly 80% less than” the originator product.

Articles

An antibody conjugate, Ujvira combines the cancer cell growth–fighting properties of trastuzumab with the cytotoxic capability of emtansine. 

Zydus Cadila Launches Trastuzumab Emtansine Biosimilar

In a study of infliximab originator vs biosimilar use, the choice of regimens was not significantly associated with treatment success at the 6-month cutoff after initiation, investigators said in findings presented at Virtual ISPOR 2021.

Patients (N = 2806) with rheumatoid arthritis who initiated or switched to infliximab originator (Remicade) or biosimilars (Inflectra, Renflexis) since December 2016 were included in the retrospective analysis. Data were retrieved from the American Rheumatology Network–Trio Health Rheumatology registry.

Investigators said 70% received originator product; 69%, Inflectra; and 31%, Renflexis. They said there were differences in demographic and baseline clinical characteristics between the reference product and biosimilar patients that were significant factors in treatment success, based on multivariable analysis.

According to the study findings, the reference product was used earlier in the treatment process than biosimilars, and a higher proportion of reference product patients were likely to be in remission or with low disease activity when treatment began (66% vs 43% for Inflectra and 43% for Renflexis) or at the 6-month cutoff (75% vs 60% for Inflectra and 56% for Renflexis).

Remicade patients had fewer prior synthetic disease-modifying antirheumatic drugs or biologic regimens (mean regimens, 1.4 vs 2.2 and 2 for Inflectra and Renflexis, respectively; 

Patients on the originator product were less likely to be covered by Medicaid (4% vs 8% for Inflectra and 24% for Renflexis). The originator product cohort also demonstrated a smaller improvement in clinical disease activity score by the 6-month point (–1.6 vs –4.9 for both Inflectra and Renflexis).

Variables that significantly affected outcomes were baseline disease activity, payer types, and use of glucocorticoids, but not the choice of a biologic drug. “Patients with high or moderate baseline disease activity on Medicaid as opposed to commercial insurance and those receiving glucocorticoids were less likely to achieve remission or low disease activity at 6 months post regiment initiation,” investigators said.

Helfgott S, Radtchenko J, Soloman N, et al. Outcomes with infliximab and its biosimilars in patients with rheumatoid arthritis: real-world experience in the US. Presented at: Virtual ISPOR 2021; May 17-20, 2021. Accessed May 21, 2021. https://www.ispor.org/conferences-education/conferences/past-conferences/ispor-2021

Adjusting for variables, investigators found little difference in disease outcomes for patients who switched to the infliximab originator vs biosimilars.

Infliximab Study Yields Evidence of Biosimilar Equivalence

Prestige BioPharma, a Singapore-based company that has a trastuzumab biosimilar (HD201) under regulatory review, said it will build a $152 million research and development facility measuring 45,000 square meters in Busan, Republic of Korea.

The company recently signed a memorandum of understanding with the Busan City government, which in this project is celebrating the construction of its first biopharmaceutical center. Prestige said it would staff the facility over the next 5 years with 209 workers with PhDs and research and development skills.

HD201 recently completed a phase 3 clinical trial and is under review for approval by the European Medicines Agency (EMA). The Prestige pipeline also includes bevacizumab (HD204) and adalimumab (PBP1502) biosimilar candidates. HD204 is in phase 3 development, and the adalimumab candidate is in phase 1.

In addition, Prestige has a first-in-class antibody (PBP1510) under development for pancreatic cancer that targets pancreatic adenocarcinoma upregulated factor. The drug has received orphan designations from the FDA, the EMA, and the Korean Ministry of Food and Drug Safety. These designations streamline the development and review processes that precede marketing approval.

Prestige has also begun a venture into vaccine development and production and participated in the production of Russia’s Sputnik 5 COVID-19 vaccine.

“Prestige BioPharma will be able to accelerate the development of innovative antibody drugs and at the same time contribute to the growing global demands of vaccines in response to COVID-19 and potential future pandemics,” said Lisa S. Park, CEO, in a 

In April 2021, Prestige announced an agreement with Pharmapark, of Moscow, Russia, for the distribution of Prestige’s HD204 in Russia. The monoclonal antibody inhibits the growth of tumors and is useful in the treatment of multiple forms of cancer, including colorectal cancer, non–small cell lung cancer, and kidney cancer, among others.

For more about Prestige BioPharma's growth strategy, click 

Prestige BioPharma aims to expand its drug pipeline with a $152 million research and development facility.

Prestige BioPharma Plans Investment to Boost Its Drug Pipeline

If biosimilar producers are looking to turn a corner in 2021, there’s hope as markets recover from the pandemic, according to panelists who reflected on barriers to uptake and opportunities to expand the use of these alternatives to costly originator biologics. 

Employing lower-cost biosimilar medicines can enable health care institutions to recover financially from the revenue drains of the COVID-19 pandemic, the speakers said. In Europe as in the United States, there remains much room for biosimilar uptake, according to Rebecca Guntern, head of Europe operations for Sandoz.

Guntern joined many authorities from industry and patient advocacy groups in the recent Reuters/Sandoz conference on biosimilar use. They discussed biosimilar advancement in the United States, European Union, and Canada.

“If you compare the Nordic countries where we see biosimilar adoption rates of about 90% and move to Eastern Europe, such as Poland, where less than 1% of the population has access to biologics, this is the gap we really need to close to ensure equality of access to health care; so biosimilars, in a nutshell, if we can unlock them, can really contribute to accelerate recovery,” Guntern said.

This can be accomplished in part by a program of education that targets everybody from prescribers to policy makers to patients, she said. “They really need to understand the benefit and the value of biosimilars."

“It’s a good time to point out that there’s a collective clinical and cost benefit to biosimilars in the US market and partner with health care institutions to really bring them to market faster,” said Robert Spina, vice president of Marketing and Market Access and Patient Services at Sandoz US.

Without good education on biosimilar use, physicians are not liable to be motivated to use them and they’re not going to be able to explain them to patients.

“They need to be convinced that these are a very good solution for their patients,” said Antonella Cardone, director of the European Cancer Patient Coalition.

In the European Union, where public health is often heavily subsidized, patients can be supportive of biosimilar use because they know that lowering the overall cost of health care means that access can be extended to more patients who need it, Cardone said. “We do believe one of the main potentials of biosimilars is to reduce disparities in access to biological cancer medicines and improve overall survival rates in Europe. For us, this is very, very important.”

Another driver could be incentives such as are employed in France, such as a “gain share model” in which institutions that use biosimilars will receive a share of the savings from the use of those agents, Guntern said.

The COVID-19 pandemic has left an “overhang” of untreated patients with cancers that have gone undetected, said panelist Murray Aitken, executive director of the IQVIA Institute for Human Data Science.

Having not received adequate care during the pandemic, many will present with more advanced disease and require an advancement directly to biologics in the first-line setting, Aitken said. “That represents an important opportunity for the biosimilars market.”

Adoption rates of 50% to 70% for biosimilars in immunology have been estimated in the European Union, but “in some countries the rate of adoption is extraordinarily high and in others it’s very low or nonexistent, said Pierre Bourdage, head of Global Biopharmaceuticals for Sandoz.

Often, this is partly due to a lack of central administration. For example, he said, hospitals have the advantage of being able to direct the use of medications by policy, but outside of those settings, “you’re really relying on the individual actions of health care practitioners directly with their patients.”

Beyond Europe, Canada is making good progress with biosimilars, Bourdage said. A native of Canada, Bourdage pointed to the success story of 

, which instituted mandatory switching to biosimilars in May 2019 for patients with ankylosing spondylitis, rheumatoid arthritis, psoriatic arthritis, plaque psoriasis, and diabetes. The British Columbia public health system, PharmaCare, expects to save up to $80 million alone by 2024 by switching 6000 patients to biosimilar forms of adalimumab.

The United States is not generally described as a biosimilar success story, but it is not to be dismissed, said Christine Simmon, senior vice president of Policy and Strategic Alliances for the Association for Accessible Medicines and executive director of the Biosimilars Council.

“The United States only came to the party in 2015 with the launch of Sandoz’ Zarxio, and so it stands to reason there’s a great deal of opportunity here,” she said.

There are at least 80 biosimilar candidates under review at the FDA, representing 45 reference biologics, Simmon said. “This could translate into US sales in excess of $80 billion by 2024 and, even more importantly, savings exceeding $100 billion in that same period of time, but it is dependent on some changes.”

Those changes, she said, would include more than getting biosimilars through the FDA review process and onto market. They include incentivizing provider adoption and payer promotion of biosimilar use. Beneficiaries in federal health coverage programs also need encouragement to use biosimilars, she said.

What distinguishes the successful biosimilar adopters from the unsuccessful is invariably “political will,” said Arnold G. Vulto, PhD, a hospital pharmacist and founder of the health care/biopharmaceutical consultancy VuPEC. “What we see is that the wealthy countries in the western part of Europe are better organized and have a stronger political will than the countries in Eastern Europe, and in many Eastern European countries, the uptake of biosimilars and even the availability of biosimilars is a lot lower, and they pay the highest price. It’s unbelievable.”

In the European Union, where countries rely on “tender” systems that may grant virtual exclusivity of market to a single biosimilar producer, reforms are needed to raise these systems to the level of “innovative, smart, and sustainable procurement,” Guntern said. “We see many cases still where the winner takes all, which means there’s only 1 company at the end that is being selected to deliver the biosimilars, and I think we need head-to-head competition.”

Sustainable markets for biosimilars are the ones that encourage the awarding of tenders to multiple bidders, as opposed to single winners, said Aitken. “Those in many ways discourage players from wanting to bid for those tenders and therefore it actually reduces the amount of competition in that market, and that doesn’t help the health system that’s operating there. We think that sort of suboptimizes the contribution that biosimilar are able to make.”

For reading on Europe's first 15 years of biosimilars, click 

Biosimilar education can increase physician motivation to prescribe these alternatives to costly originator products, panelists said in a Sandoz/Reuters discussion.

Sandoz Panel Describes Issues, Opportunities for Biosimilars

Investigators in Quebec, Canada, say they have found significant costs associated with nonmedical switching (NMS) from originator products to biosimilars in patients with rheumatic conditions. The findings were presented at Virtual ISPOR 2021.

Although the direct costs of switching from an originator to a biosimilar are expected to be lower, given the relatively high costs of originator brands, switching is accompanied by costs of patient evaluations, lab tests and X-rays, additional time spent by health care professionals on education, documentation, hospitalization, emergency department use, workplace productivity loss, and other societal and health care resource utilizations (HCRCs) .

“The true economic impact of originator-to-biosimilar NMS requires the assessment of the difference in costs related to HCRU in addition to those related to the originator and biosimilar drugs themselves,” authors of the study wrote.

The emergence of the study has potential significance for Quebec as it has just announced intentions to 

 most patients from originator biologics to biosimilars with an anticipated savings of US $83 million by 2022. Although the study evaluated HCRU in patients with rheumatic disease, it did not disclose the originator and biosimilar agents included in the analysis.

The study was funded by AbbVie and conducted in part by researchers from AbbVie Canada and from Peripharm, a company that consults with AbbVie and receives AbbVie funding. AbbVie manufactures the adalimumab originator (Humira), indicated for the treatment of rheumatic diseases and ulcerative colitis, and has much at stake in the mandatory switch from originator biologics to biosimilars currently underway in Quebec and 3 other Canadian provinces.

The study findings were reported in Canadian dollars and converted to US dollars for this article. According to results of the study, nonswitchers were associated with HCRU-related costs over a 6-month period of $435 vs $1036 for switchers. Nonswitchers were associated with societal costs over a 6-month period of $1024 vs $1509 for switchers. The total HCRU and societal costs were $1423 vs $2545 for nonswitchers vs switchers, the authors said.

“A patient undergoing an originator-to-biosimilar NMS will incur an additional $1087 over a 6-month period in comparison to patients who remain on the originator,” they said.

Investigators said the main drivers of the difference in costs between those who remained on originators vs those who switched were hospitalization and productivity loss, “with added costs of $465 and $297, respectively, for patients undergoing an originator to biosimilar NMS,” they said.

Other types of costs bear consideration, such as costs associated with adverse events and government costs of implementing an NMS policy, such as physician paid incentives. “It is possible that patients who undergo an originator-to-biosimilar NMS in Quebec are associated with greater costs than what is reported in the current study,” the authors said.

They drew their data from Quebec sources that included governmental publications. They also cited prior UK and Denmark studies of costs associated with nonmedical switching of patients from originator to biosimilar etanercept, a product that also is used for rheumatic diseases and competes with adalimumab.

In the UK study, investigators used a model based on prior data to estimate costs for hypothetical patients who switched from originator etanercept to 1 of 2 etanercept biosimilars (Benepali and Erelzi). Some were assumed to have switched back to the originator or from one biosimliar to the other. A nonresponder population was included, and it was assumed that some patients switched to other types of biologic agents.

 “considerable increases in resource use (procedures and visits) for switching vs nonswitching patients,” although annual per patient costs of Benepali and Erelzi were 92% and 90% of the costs of etanercept originator, respectively.

“Nonmedical switching can result in increased costs to health care payers because of increased healthcare resource use following switching; therefore, switching should be a medical decision based on clinical evidence, and driven by physician decision in collaboration with the patient. Further analyses of the impact of nonmedical switching of etanercept in different markets and over longer time periods are required,” the UK study authors wrote.

 (N = 1620) did a 1-year follow-up of a government-imposed switch of patients with rheumatic conditions from originator etanercept to biosimilar (Benepali). Investigators reported modest increases in use (8%) and costs (7%) of outpatient services after switching, “whereas costs of admissions (55%) and medication (5%) decreased.”

“We demonstrated no obvious changes in overall use and costs of health care services following switch from originator to biosimilar etanercept,” the authors wrote.

Mathurin K, Castonguay A, Parison D, et al. Economic impact of originator-to-biosimilar non-medical switching on health care resource utilization in rheumatic patients in Quebec, Canada. Presented at Virtual ISPOR 2021; May 17-20, 2021. Accessed May 19, 2021. https://www.ispor.org/conferences-education/conferences/upcoming-conferences/ispor-2021

A study funded by AbbVie finds support for maintaining patients on originator rheumatic agents, such as Humira (adalimumab), rather than switching to biosimilars.

AbbVie Study Highlights Switching Costs for Rheumatic Biosimilars

Quebec has become the fourth Canadian province to implement a mandatory biosimilar switching program. With some exceptions, the province is switching to a policy of allowing only biosimilars, if available, on lists of approved biologics.

“Thus, depending on the option considered, patients who use a reference biological drug, for which one or more biosimilar drugs are registered, will have to switch to one of these by April 12, 2022, under the supervision of their doctor,” said Minister of Health and Social Services Christian Dubé 

Manufacturers of reference biologics “have been informed of this shift” and “discussions will take place with the main partners and associations of the health and social services network on this subject in the coming weeks,” the statement said.

The province anticipates US $83 million in annual savings by 2022. Officials said the move follows failure to achieve sufficient uptake of biosimilars in Quebec even though they have been recommended by the National Institute of Excellence in Health and Social Services and placed on drug formularies “for many years.”

“This situation generates a considerable additional cost for the general drug insurance plan because biosimilar drugs are significantly less expensive than reference drugs, with no difference in [quality of] therapy for patients," according to Dubé.

Innovation is giving rise to incredible medical advances and the development of health care practices and services that are always better suited to people’s needs. The decisive shift we are taking toward the judicious use of biosimilar drugs is a good example of this.

Canadian health authorities stressed that biosimilars are safe and effective, proven similar to originator brand drugs, and authorized by use by the public health authority Health Canada. In 1997, Quebec adopted a general prescription drug insurance plan that provides universal health coverage for all citizens of the province. The cost of this plan from 2019 to 2020 was $5.1 billion.

Health Canada has approved 36 biosimilars for 14 innovator products. There are 13 other biosimilar candidates under review, and these include 5 bevacizumabs and 2 adalimumabs, according to an 

 by Smart & Bigggar, an intellectual property law firm. Regulatory reviews of biosimilars in Canada generally take about a year, although some are considerably longer. 

“Innovation is giving rise to incredible medical advances and the development of health care practices and services that are always better suited to people’s needs. The decisive shift we are taking toward the judicious use of biosimilar drugs is a good example of this,” Dubé said.

Biosimilars Canada, a trade group representing biosimilar distributors and manufacturers, applauded the move.

“These savings will be reinvested into the health care system and will also improve access to innovative drug therapies,” 

Under the policy, patients who are being treated with an originator biologic drug for which a biosimilar biologic drug is available will switch to a biosimilar under the supervision of their treating physician by April 12, 2022.

“Biosimilar switching policies are essential to ensuring the long-term sustainability of drug benefit plans and health care systems,” said Jim Keon, president of Biosimilars Canada.

Quebec follows British Columbia, Alberta, and New Brunswick in implementing the biosimilars plan. Biosimilars Canada indicated that residents of Quebec were 85% in favor of a switching policy according to a recent poll.

Read about the New Brunswick, Canada, switch to biosimilars 

Read about Amgen Canada's launch of an adalimumab biosimilar 

Biosimilars were on formulary for years but nobody was using them, Canadian authorities explain as their reasons for dropping originators from approved lists.

Quebec Makes It Harder to Use Originator Biologics

Various House members have asked the Federal Trade Commission (FTC) to open an antitrust investigation into pharmaceutical giant AbbVie, which allegedly has exceeded its patent rights in preventing biosimilar competition to arthritis drug Humira (adalimumab) in the United States.

The request follows the release of a report from the House Committee on Oversight and Reform that outlines attempts by AbbVie to prevent competition and thereby reap $107 billion in US revenues alone since 2003. Biosimilar competitors have attempted to enter the US market but have been delayed until 2023 by AbbVie litigation and negotiated settlements.

“We make this request in light of previously non-public documents obtained by the Committee on Oversight and Reform during its multi-year investigation of AbbVie,” the members 

“Based on our review, these documents indicate that AbbVie delayed biosimilar competition for far longer than warranted by its own internal evaluations of the strength of its patent portfolio, which anticipated biosimilar entry no later than 2017.”

The FTC request was authored by Representatives Carolyn B. Maloney, D-New York, chairwoman of the Committee on Oversight and Reform; Jerrold Nadler, D-New York, chairman of the Committee on the Judiciary; and David N. Cicilline, D-Rhode Island, chairman of the Committee on the Judiciary’s Subcommittee on Antitrust, Commercial, and Administrative Law.

The request preceded a daylong hearing involving testimony and inquiry into AbbVie’s pricing and marketing practices, during which AbbVie CEO Richard Gonzalez also testified. Audience members heard expert opinion and also commentary from patients who said that AbbVie’s pricing policies for Humira had placed this drug beyond their reach or forced them to make very difficult tradeoffs. The report stated that AbbVie now charges roughly $77,000 for an annual supply of Humira, 470% higher than when the drug was launched in 2003.

Katherine Pepper, of Bellingham, Washington, said she suffers from debilitating pain and reduced mobility caused by psoriatic arthritis. She was prescribed twice-weekly Humira injections, costing $5900 for a pack of 2 injection pens. “Even as a Medicare beneficiary on a fixed income, I still have to pay nearly $1200 out of pocket every single month,” she said. “I can’t afford this. I don’t know any average person who can. The excessive Humira price forces me to choose every month whether to eat or fill my prescriptions. This company’s price gouging needs to stop,” she said.

For an overview of the House committee’s investigative report on AbbVie, which reviewed 170,000 pages of internal company documents, click 

In his testimony, Gonzalez stated that much of AbbVie’s revenues go toward research and development into new products that might yield substantial benefit for patients—$50 billion since 2013. “As we tackle the issues of drug pricing and access, it’s important that we focus on what’s working and what needs to change to make sure that patients get the medicines they need,” he said.

Gonzalez said a major culprit for the payment gap suffered by patients is the Medicare Part D program, which he said fails to cover drugs costs adequately. “For these patients, reducing drug prices alone will not alleviate the challenge of access and affordability,” he said.  

“What’s not working in Part D is that some patients must bear too much of the out-of-pocket cost, and there’s no cap on drug spending. Part D enrollees cannot access co-pay support, they cannot purchase insurance to defray these costs, and they must pay open-ended drug expenses. The average out-of-pocket cost is almost 100 times higher for a medicine like Humira than any other US patient group. No other prescription drug insurance program puts so much cost burden on the patient,” he said.

AbbVie does have a patient assistance program, and 1 out of 3 patients in Part D are seeking assistance or receiving free medicine, he said. This “stands in stark contrast” to commercially insured Humira patients. One out of 100 seek assistance from the AbbVie patient assistance program, he said. “Medicare Part D patients’ out-of-pocket costs are the single biggest issue when it comes to drug affordability.”

Accused of unfair trade practices, AbbVie's CEO Richard Gonzalez pointed the finger at Medicare Part D. 

AbbVie's Gonzalez Is on Defense as House Members Petition FTC

 from the House Committee on Oversight and Reform describes a “cold and heartless” methodology allegedly employed by AbbVie to keep biosimilar competition away from its increasingly lucrative adalimumab (Humira) franchise. There aren’t any adalimumab biosimilars on the US market currently, although 6 have been approved by the FDA.

AbbVie’s CEO Richard Gonzalez is on the hot plate this week as the House committee questions him and hears testimony from various opponents to adalimumab patent exclusivities that have helped AbbVie receive $170 billion in worldwide net revenue from Humira since 2003, “including $107 billion from the US health care system,” according to the report. 

 requested comment from AbbVie prior to publication but there was no response.

AbbVie has at least 136 US patents protecting adalimumab and most recently has asserted 62 of them in a battle with Icelandic company 

, which seeks to bring a high-concentration formulation of adalimumab to market.

The Humira company has at times even surprised itself with the cleverness of its biosimilar competition defense strategy, the House report alleges, citing internal documents it obtained from AbbVie.

“In 2014, AbbVie’s executives estimated that 3 to 5 biosimilar competitors would enter the market by the first quarter of 2017, [but] AbbVie ultimately entered into settlement agreements with 4 of these competitors, delaying their entry into the market until 2023,” the report said, citing AbbVie documents. In fact, the company has delayed entry until 2023 for all 6 adalimumab biosimilars currently approved for the US market.

Part of this strategy was to “raise barriers to competitor ability to replicate” adalimumab, the report said, citing language used by AbbVie employees in documents. The House report contends these barriers included filing hundreds of patent applications for Humira, in the hopes that many would stick, and launching follow-on products that kept the core adalimumab franchise out of reach of competitors. For example, high-concentration Humira was introduced in 2018 and has captured a large share of the adalimumab market. The product’s advantage was a reduction in pain upon injection.

“If AbbVie had truly developed the concentration formulation to reduce pain for patients, it would have launched the drug immediately. Instead, AbbVie held the formulation off the market until July 2018, possibly waiting until biosimilar manufacturers had invested significant resources in developing biosimilar versions of the original formulation of Humira,” the report alleged.

Through regular and frequent price increases, along with an expanding market for adalimumab, AbbVie has succeeded in increasing its annual US Humira revenues from $200,000 in 2003 to $16.1 billion in 2020. The report contends this was partly accomplished by tying executive compensation at the company directly to Humira net revenue.

“The first year this net revenue incentive was added to the calculation coincided with the highest period of price increases in Humira’s history—over 30% in a 10-month period,” the report said.

AbbVie has raised the price of Humira 27 times, so that a 40-mg/mL syringe of adalimumab in the United States is now priced at $2984 ($77,586 annually), which represents a 470% increase from when the drug launched in 2003. Meanwhile, Humira prices in the European Union, where adalimumab biosimilars have been marketed, are often less than half or one-third the cost of adalimumab in the United States. 

Another allegation in the report suggests, if not price fixing, an unspoken collaboration with a competitor to avoid allowing either company’s product to undersell the other. The report states that Humira’s closest competing drug is Amgen’s etanercept (Enbrel), which also has full exclusivity in the United States, owing to patent protections.

“Instead of pricing Humira and Enbrel below one another to gain market share—as expected in a competitive market—AbbVie and Amgen engaged in a practice known as 'shadow pricing,' consistently following the other company’s price increases.”

From 2003 to 2021, the prices of Humira and Enbrel mirrored each other almost exactly throughout dozens of price increases, according to the report (

The House report also describes similar practices for another AbbVie blockbuster drug, ibrutinib (Imbruvica), a small molecule product used for the treatment of hematologic cancers.

“These price hikes contributed to billions of dollars in corporate profits and enriched company executives while harming American patients and taxpayers,” the report said.

The House Committee on Oversight and Reform contends AbbVie's "biosimilar defense strategy" has succeeded beyond the company's wildest imagination. 

House Committee Issues Blistering Report on AbbVie's Humira Tactics

In an action that comes at a key time in the debate over product exclusivity and patient access, Sandoz, a Novartis division, has l

 to bring its etanercept biosimilar Erelzi to market before 2029, as the high court declined to review the company’s petition to invalidate 2 patents held by the originator company Amgen for the reference drug, Enbrel. 

The originator product has garnered billions of dollars in yearly revenues over 22 years of product exclusivity in the United States so far.

Enbrel is a tumor necrosis factor inhibitor that was first approved in 1998. It is currently indicated for rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, and plaque psoriasis. The product brought in $4.9 billion in revenues for Amgen in 2020, down from $5.2 billion in 2019. There are 3 approved etanercept biosimilars in the European Union, the earliest of which (Benepali) was launched in January 2016.

In the United States, Erelzi got FDA approval in August 2016 and Samsung Bioepis received approval for its etanercept biosimilar (Eticovo) in April 2019, but patent exclusivities are holding that off the market, too.

In its legal effort, Sandoz had targeted patents asserted by Amgen in defense of Enbrel’s exclusivity, namely US Patent 8,063,182, covering the fusion protein etanercept, and US Patent 8,163,522, covering a manufacturing process. The patents are 

“We are disappointed the Supreme Court decided not to review our case,” said Keren Haruvi, president of Sandoz US and Head of North America. “Today’s decision means Erelzi, a more affordable biosimilar, will not be available to US patients with autoimmune and inflammatory diseases until 2029; nonetheless we remain committed to providing important treatment options for patients affected by these diseases.”

Sandoz was the first company to receive FDA approval for an etanercept biosimilar. The other was Samsung Bioepis, which saw its Eticovo product approved in April 2019.

The Supreme Court bid by Sandoz was an appeal of a Federal Circuit court 2-1 ruling in mid-2020 that upheld the 2 patents in question. Previously, a US District Court judge found that Sandoz had failed to demonstrate that the patents were invalid.

Whatever the merits of the case, the highest court’s decision not to review the etanercept patents intensifies the spotlight already on originator products that enjoy lengthy periods of exclusivity and that prevent competitors’ products from entering market at lower cost and thereby improving access to health care for patients.

On Tuesday, May 18, 2021, Richard Gonzalez, CEO of AbbVie, is 

 before the House Oversight Committee on his company’s exclusivity protections for adalimumab (Humira), a blockbuster drug that has been available in the European Union since 2018, but not in the United States, where the first of 6 adalimumab biosimilars was approved in 2016. Each of the 6 adalimumab biosimilar developers has settled out of court with AbbVie rather than pursue a patent battle with the company, which according to Gonzalez has at least 136 patents protecting its lucrative adalimumab franchise.

Most recently, Alvotech of Reykjavik, Iceland, 

 with AbbVie over a high-concentration formulation of adalimumab. AbbVie filed suit against Alvotech alleging the company stole trade secrets regarding the manufacturing process for this formulation, and Alvotech sued in return, alleging that AbbVie’s patents are invalid.

Return to The Center for Biosimilars® website later this week for further coverage of these issues. 

Originator company Amgen has won another round in defending its lucrative etanercept franchise, but the decision is sure to intensify scrutiny of extended patent protections. 

Sandoz Is 0-3 in Enbrel Patent Case

Investigators in Germany said that a comparison of adalimumab biosimilar (Amgevita) vs originator (Humira) treatment for patients with rheumatoid arthritis (RA) has demonstrated significant cost savings both for earlier treatment overall and for use of the lower-cost biosimilar vs the originator product.

Findings were presented at the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 2021 virtual meeting, May 17-20, 2021.

RA is a chronic autoimmune condition associated with persistent joint inflammation, organ involvement, significant comorbidities, and “considerable adverse physical, economic, emotional, and social consequences,” authors of the study said. “The negative impact of RA can be cumulative over the course of a patient’s life.”

Investigators sought to weigh the economic effect of delaying the start of biologic treatment for RA and the potential savings from earlier treatment with adalimumab, which would be more feasible with the biosimilar than originator product because in Germany at current prices Amgevita is cheaper than Humira, investigators said.

They said that a 6-month delay in initiation of treatment with biologics was associated with cumulative incremental costs of $8177 per patient, which included loss of productivity. After 3 years, the cumulative costs of delayed treatment were more than $12,146 per patient; after 8 years, the cumulative costs were more than $24,291.

In addition, use of the biosimilar vs the originator product resulted in an overall lifetime reduction in costs (including drug costs, medical resource use, indirect costs, and monetized health outcomes) of $30,519 per patient, and this calculation is based on a 6-month delayed initiation of treatment for the more-costly originator product. This figure also represents a lifetime reduction in drug cost of $26,823 (Amgevita, $199,478; Humira, $226,303). Note that figures were converted from Euro values and rounded. 

“Excluding the monetary value of health outcomes, cost neutrality compared with later treatment with adalimumab at current originator pricing was estimate to be achieved treating 3 years earlier, assuming patients are eligible to receive biologic treatment at that time,” authors concluded.

Investigators said significant savings on hospitalization and productivity loss were possible by initiating treatment earlier in the disease cycle.

“The model demonstrated the value of biologic treatment for eligible patients with RA and that avoiding delays in the initiation of biologic treatment could be cost saving,” they said. “Treating patients earlier may result in better health outcomes in the long term.”

Further, they concluded, “The costs of treating eligible patients earlier with Amgevita at current pricing levels are expected to be offset by later cost savings.”

In the European Union, competing biosimilar forms of adalimumab have been approved for use since 2017. In 2018, non-US sales of Humira peaked at $6.25 billion and began a swift decline. They measured $4.3 billion in 2019 and $3.7 billion in 2020. For a list of approved adalimumab biosimilars in the European Union, click 

Porter J, Stuart P, Bartsch R, Lebioda A. cost-effectiveness analysis of adalimumab biosimilar compared to delayed biologic treatment initiation in patients with rheumatoid arthritis in Germany. Presented at: Virtual ISPOR 2021; May 17-20, 2021. Accessed May 16, 2021. https://www.ispor.org/conferences-education/conferences/upcoming-conferences/ispor-2021

Investigators evaluated both biosimilar vs originator savings and savings from earlier use of a lower-cost adalimumab biosimilar (Amgevita).