Cameron Santoro is an associate editor for The Center for Biosimilars

Cameron Santoro

Here are the top 5 biosimilar articles for the week of January 20, 2025. 

 (PBMs) increased many specialty generic drugs prices by hundreds of percent, with some drugs seeing thousands of percent markups, according to the Federal Trade Commission (FTC)’s second interim report on PBM practices.

: Achieving global regulatory harmonization for 

 is essential to improving market access, reducing costs, and enhancing patient outcomes by streamlining approval processes, fostering international collaboration, and addressing regulatory disparities.

 from Humira (reference adalimumab) to biosimilar adalimumab in Denmark led to no increase in total health care costs over 9 months, with significant cost reductions for those who switched to GP2017 specifically, highlighting the economic feasibility of biosimilar adoption.

: Biosimilar launches achieve a 53% market share and a 53% reduction in average drug costs after 5 years of biosimilar competition, according to 

Samsung Bioepis’ most recent market report

, showcasing notable pricing trends and market share disparities across therapeutic areas.

 has rapidly evolved since its launch in 2017, driven by steep price discounts, payer adoption, and provider confidence, with an upcoming wave of biosimilars targeting blockbuster biologics promising further market growth, cost savings, and broader patient access.

To read all of these articles and more, visit 

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The Top 5 Biosimilar Articles for the Week of January 20

Here are the top 5 biosimilar articles for the week of January 13, 2025. 

: Korean drugmakers hold over 50% market share in the 6 best-selling 

, 2 companies sign exclusive licensing partnership for a denosumab biosimilar, and 2 others join forces for an eculizumab biosimilar.

 demonstrated equivalent efficacy, safety, and immunogenicity compared with the originator in a phase 3 trial involving postmenopausal women with osteoporosis, paving the way for improved accessibility and cost savings in osteoporosis treatment.

 to mirror successful outcomes across Europe could significantly accelerate US biosimilar market entry.

: Sarfaraz K. Niazi argues that the Indian Central Drugs Standard Control Organisation 

(CDSCO) Biosimilar Guidelines need revision

 to align with current scientific understanding and focus on better manufacturing practices.

 showed biosimilar CT-P42 (Celltrion) is therapeutically equivalent to reference aflibercept in improving visual acuity in patients with diabetic macular edema (DME), with comparable efficacy, safety, pharmacokinetics, and immunogenicity at 24 weeks, with more long-term data expected.

The Top 5 Biosimilar Articles for the Week of January 13

A study from Spain found a subcutaneous tocilizumab biosimilar to be cost-effective when treating patients with RA after experiencing improved outcomes. | Image Credit: andranik123 - stock.adobe.com

Biosimilar tocilizumab (RoActemra; TCZ) improved outcomes of patients with rheumatoid arthritis (RA) living in Spain and saved health care costs compared with other treatments, suggesting a promising avenue for enhancing patient care and optimizing resource allocation, according to a study published in 

Patients diagnosed with RA experience high economic and humanistic burdens based on increased costs for the appropriate management of the disease and the associated morbidity. In Spain, about 5% of the total burden of rheumatic diseases are a result of RA. The prevalence of RA is increasing while mortality is decreasing, mainly in high-income countries where better management of disease control is practiced.

The development of biological disease modifying anti-rheumatic drugs (bDMARDs) altered the treatment paradigm 20 years ago, leading to improvements in disease control, less steroid consumption, and the attainment of a better overall quality of life. Disease effect and its progression are largely impacted by the bDMARDs. 

The European Commission approved TCZ for the treatment of moderate-to-severe RA in 2009 under Roche manufacturing.

 TCZ is noted as the first interleukin-6 receptor and inhibits monoclonal antibodies. The drug is indicated to be combined with methotrexate among patients with RA who responded inadequately or were intolerant to bDMARDs or tumor necrosis factor-α antagonists.

The current biosimilar therapeutic alternatives for RA management include abatacept, adalimumab, baricitinib, certolizumab, etanercept, golimumab, infliximab, rituximab, sarilumab, tofacitinib, upadacitinib, and TCZ.

The study aimed to develop a cost-effectiveness analysis of subcutaneous biosimilar TCZ for the treatment of RA compared with the most common alternatives in Spain through a health care lens.

The systemic literature review included 13 studies that demonstrated efficacy, meta-analyses, and a series of clinical trials for alternative treatments. The Disease Activity Score 28 (DAS28) had thresholds for each of the 4 health status categories: remission (DAS28 < 2.6); low disease activity (2.6 ≤ DAS28 ≤ 3.2); moderate disease activity (3.2 < DAS28 ≤ 5.1); and high disease activity (DAS28 > 5.1).

After 52 weeks of treatment, better performance was recognized after TCZ, upadacitinib, certolizumab, and filgotinib use. Patients with moderate-high disease activity status at 52 weeks were treated with rituximab, golimumab, and etanercept.

Higher levels of remission status were found among patients taking upadacitinib (12.67%), TCZ (12.61%), and sarilumab (12.58%). The quality-adjusted life years (QALYs) were 13.73 for both TCZ and sarilumab while upadacitinib obtained 13.74 values. Biosimilar TCZ had the lowest total cost per patient (€183,741), followed by infliximab (€184,317). Certolizumab displayed the highest cost per patient (€201,972) compared with biosimilar TCZ and infliximab.

The incremental cost-effectiveness ratio for patients in remission health status or QALY showed the biosimilar TCZ was either dominant or cost-effective compared with the alternative drugs. The most influential factors in variability of the results were the probability of transition from remission to low disease activity health status, long-term costs of biosimilar TCZ, and probability of transition from low to moderate disease activity health status.

Across all scenarios, biosimilar TCZ was the most cost-effective treatment option. There was a 100% chance biosimilar TCZ was cost-effective when compared with the other treatment options for both the €30,000 and the €22,000 thresholds that Spain uses often.

The ex-factory prices are used in this analysis because final reimbursed prices are not publicly available, which could have impacted the results. Biosimilars should be utilized earlier in the treatment setting to leverage all potential benefits. Reports in Spain have found increased biosimilar adoption would allow additional patients to be treated by redirection of savings, improved health care resource allocation, and better patient care.

Pérez-Ruiz F, Crespo-Diz C, Schoenenberger-Arnaiz JA, et al. Cost-effectiveness analysis of subcutaneous biosimilar tocilizumab in patients with rheumatoid arthritis in Spain. 

. Published online December 1, 2024. doi:10.1016/j.farma.2024.11.004

Nataloni R. Tocilizumab approved for rheumatoid arthritis in Europe. Medscape. January 23, 2009. Accessed January 14, 2025. 

https://www.medscape.com/viewarticle/587253

Articles

A study from Spain found a subcutaneous tocilizumab biosimilar to be cost-effective when treating patients with rheumatoid arthritis (RA) after experiencing improved outcomes.

Biosimilar Tocilizumab Cost-Effective for Treatment of Rheumatoid Arthritis in Spain

The top 5 biosimilar articles for the week of January 6, 2025. 

 articles of the year highlight a significant shift in the pharmaceutical industry, with projections indicating strong uptake in biosimilars at the expense of the originator products, despite challenges like uptake disparities and safety concerns.

 for aflibercept biosimilars reflects significant progress in offering cost-effective treatments for retinal conditions like neovascular age-related macular degeneration, although patent disputes pose challenges to their market entry and adoption.

 (Celltrion) is therapeutically equivalent to reference aflibercept in improving visual acuity in patients with diabetic macular edema (DME), with comparable efficacy, safety, pharmacokinetics, and immunogenicity at 24 weeks, with more long-term data expected.

 to introduce a new bipartisan bill to protect biosimilar and generic drug manufacturers from patent litigation when obtaining “skinny label” approvals for their products.

 Sarfaraz K. Niazi argues that the Indian Central Drugs Standard Control Organisation 

Here are the top 5 biosimilar articles for the week of January 6, 2025. 

The Top 5 Biosimilar Articles for the Week of January 6

Reforming patent litigation to mirror successful outcomes across Europe could significantly accelerate US biosimilar market entry. | Image Credit: © md3d - stock.adobe.com

The biosimilar market could be accelerated through patent litigation reforms that expedite biosimilar market availability throughout the US, according to a study published in 

Between 2015 and 2021, the US only had 11 biosimilars marketed compared with the European Union, which had 55 biosimilars marketed between 2008 and 2021. Despite biosimilar approval growth in the US, delayed entry into the market due to patent litigation continues to be an issue.

Often, drug manufacturers hold patents for ingredients, known as primary patents. Other times, patents are filed based on the method of use or manufacture, formulation, route of administration, and sometimes the devices used to administer the drug.

The Current Biosimilar Litigation Framework

When biosimilars aim to enter the market, a biosimilar firm typically has 3 options. They can either preclear the patents prior to entering the market by engaging in a “patent dance” along with the associated patent litigations, launch “at risk,” or settle with the biologic brand to avoid any active patents.

Under the Biologics Price Competition and Innovation Act (BPCIA), the patent dance was designed. This process consists of a structured legal process that aims to streamline patent disputes among biosimilar manufacturers and reference product sponsors.

 Created as part of the BPCIA, the patent dance helps expedite biosimilar entry into the market while balancing the interests of innovators who originally developed the biologic therapies.

The patent dance comes into play when a biosimilar manufacturer submits an FDA approval application and includes an exchange of information with the intention to provide clarity regarding which patents may be relevant for litigation.

Branded drug companies request preliminary injunctions to try to maintain the brand biologic’s market exclusivity until the completion of patent litigation. Once both litigation suits are resolved, the biosimilar firm will know if it can launch the product free from patent risk. 

When manufacturers launch the biosimilar during ongoing litigation, it is referred to as “launching at risk” because if the biosimilar is shown to have infringed on the patent, it could lead to lost profits totaling exceeding millions of dollars. This typically leaves biosimilar firms in difficult situations when they receive FDA approvals for products with litigation still pending.

Shifting Litigation for Expedited Biosimilar Market Entry

Early patent litigation during biosimilar phase 3 trials could facilitate timely market entry, mirroring generic drug practices. However, this approach could face judicial challenges related to ripeness; the 

 case suggests these challenges are surmountable. The case led to the Supreme Court ruling declaring follow-on biologic companies are not required to share their licensing application with the innovator company, as long as there is an additional mandatory 180-day notice to the innovator prior to commercial marketing for the FDA to approve the product.

However, altering clinical trial requirements to accommodate earlier litigation may be impractical due to the need for extensive data and potentially costly modifications.

By allowing patent litigation to begin earlier, biosimilars could have the opportunity to challenge patents at the beginning of the phase 3 clinical trials.This process would help with market entry during the primary patents’ expiration, a parallel of the generic market entry process.

To assess the potential benefits of earlier litigation, the present researchers analyzed biosimilar patent litigation data from 2010 to 2022 using the Lex Machina database to estimate potential cost savings.

Of the 54 biosimilars that initiated phase 3 trials, 92% resulted in a sufficient amount of information to begin litigation without worry of wasting court resources. Between 2010 and 2022, 95 biosimilars were identified in association with 25 brand biologics that reached initiation phase 3 development. 

Data included 59 biosimilars that might have failed to receive FDA approval during a phase 3 trial. This comprised 61% that launched in the US, 31% undergoing litigation, 2% that failed the trial, and 7% that provided limited information. Overall, 92% went on to submit at least 1 dossier to the FDA, leaving court resources unwasted if patent litigation began at initiation of the phase 3 clinical trial.

There were 32 biosimilars that entered the market between 2010 and 2022 with completed judicial proceedings. Sixteen percent of them won in litigation against the brand biologic, 9% lost, and the remainikng 75% settled. On average, litigation duration is 2.9, 0.95, and 4.2 years for biosimilar wins, settlements, and losses, respectively. From patent expiry to biosimilar launch, the correspondig average duration is 2.3, 2.5, and 16.5 years when biosimilars win, settle, or lose litigation.

The BPCIA, intended to facilitate biosimilar market entry, has fallen short of achieving the same level of market penetration as generic drugs. This disparity largely stems from the stringent clinical trial requirements imposed on biosimilars, significantly delaying their market entry compared with generic medications.

Many European countries, including the United Kingdom, have the same patent litigation pathway for both generics and biosimilars. Both drug manufacturers are allowed to litigate the validity of patents at any point during the product’s development program. Experts like Sarfaraz K. Niazi, PhD, 

 adopt the same system as the UK’s Medicines and Healthcare Products Regulatory Agency surrounding unnecessary clinical efficacy testing.

“To fulfill the intended objectives of the BPCIA, Congress should create a two-track system that grants biosimilars the option for earlier litigation,” the study authors concluded.

1. Tu S, Goode R, Turner M, Van de Wiele V. Accelerating biosimilar market access: the case for allowing earlier standing. 

. 2025;12(1):1-16. doi:10.1093/jlb/lsae030

2. Jeremias S. Breaking down biosimilar barriers: the patent system. The Center for Biosimilars

. November 11, 2024. Accessed January 7, 2025. 

https://www.centerforbiosimilars.com/view/breaking-down-biosimilar-barriers-the-patent-system

3. Sarpatwari A, Gluck AR, Curfman GD. The Supreme Court ruling in Sandoz v Amgen: avictory for follow-on biologics. 

. 2018;178(1):5-6. doi:10.1001/jamainternmed.2017.6145

4. Niazi SK. BioRationality: a critical analysis of Pfizer views on sustainability of biosimilars. The Center for Biosimilars. December 23, 2024. Accessed January 8, 2025. 

https://www.centerforbiosimilars.com/view/biorationality-a-critical-analysis-of-pfizer-views-on-sustainability-of-biosimilars

Reforming patent litigation to mirror successful outcomes across Europe could significantly accelerate US biosimilar market entry.

Earlier Patent Litigation Could Accelerate US Biosimilar Market Entry

No significant difference in the risk of serious infections between etanercept and infliximab biosimilars and their original brand-name medications was identified. | Image Credit: Ouahdou - stock.adobe.com

Patients treated with etanercept and infliximab biosimilars experience a similar risk of serious infections as those treated with the original brand-name drugs, potentially offering patients access to safe and more affordable treatment options, according to a study published in 

Biologic drugs are gaining popularity, especially for the management of autoimmune diseases like inflammatory arthritis and inflammatory bowel disease (IBD). Real-world comparative studies prioritize safety assessment, examining the long-term effects of both biosimilars and bio-originators.

Global skepticism regarding biosimilar safety persists, necessitating ongoing requirements for switching studies to ensure their efficacy and safety.

 Previous studies have found infliximab biosimilars effective and well-tolerated after switching, with no discontinuations or clinical changes within 6 months.

Following the CMS announcement that etanercept is among the 10 drugs selected for price negotiation under the Inflation Reduction Act, increased competition from biosimilars is anticipated within the next few years.

 Etanercept biosimilars are expected to launch in 2029 following the resolution of patent litigation with the original manufacturer. This delay has implications for patient access and affordability of this medication used to treat rheumatic diseases.

Administrative databases are often used as real-world data that can “enable long-term safety assessments in populations not eligible for clinical trials but at higher risk of serious infection and may capture missed rare adverse events.”

This retrospective cohort study compared the occurrence of serious infections in Canadian patients with autoimmune diseases treated with etanercept or infliximab biosimilars vs their corresponding bio-originator from 2015 to 2019. Data included the National Prescription Drug Utilization Information System linked to the hospital Discharge Abstract Database.

There were 6583 and 7202 individuals who initiated etanercept and infliximab, respectively. The etanercept cohort was mostly women with a median age of 62 and about 10% had an inflammatory arthritis diagnosis. Half of the infliximab cohort were women with a median age of 45 but only 2% were identified with inflammatory arthritis and 35% with IBD. Both cohorts had a median follow-up period of 2.2 years.

More patients taking infliximab experienced hospitalization due to infection (7%) compared with patients taking etanercept (2%). Additionally, incidence rates for serious infection among infliximab users (30 cases per 1000 person-year [PY]) was higher than it was for etanercept (9 cases per 1000 PY).

There were no clear differences identified in the risk of incidence of serious infection between biosimilar and bio-originator for both cohorts, even when adjusted for confounders. Higher infection risk was found among both etanercept and infliximab groups after independent corticosteroid use was previously noted. Older age was found to be a risk factor for infection in etanercept initiators.

Patients with inflammatory arthritis treated with etanercept (n = 695) or with infliximab (n = 154) did not have a clear difference between biosimilar and bio-originator use in terms of first serious infection. Individuals with IBD diagnosis treated with infliximab (n = 2506) did not have an established difference between biosimilar vs bio-originator in terms of serious infection.

Study limitations include potential widespread selection bias and the availability and consistency of data elements across different jurisdictions that may vary and require consideration during data analysis and interpretation. This is also like other claims databases that lack clinical and laboratory details that may neglect to fully assess disease severity and treatment response.

There are limited real-world studies that have addressed the safety of etanercept and infliximab in large populations because most of them have focused on comparing the first biosimilar to its corresponding bio-originator, often overlooking other competitors.

The study was unable to demonstrate a difference regarding hospitalized infection risk when comparing biosimilars and their corresponding bio-originators. Utilizing ongoing safety methods, “we can enhance our understanding of the safety profiles of biosimilars and foster evidence-based decision-making in managing chronic inflammatory diseases,” concluded study authors.

1. Birck MG, Lukusa L, Choquette D, et al. Incidence of serious infection among etanercept and infliximab initiators: safety comparison between biosimilars and bio-originators with Canadian population-based data. 

. 2024;8(1):47. doi:10.1186/s41927-024-00415-5

2. Jeremias S. New evidence confirms safe biosimilar-to-biosimilar switching. The Center for Biosimilars

. May 28, 2024. Accessed January 2, 2025. 

https://www.centerforbiosimilars.com/view/new-evidence-confirms-safe-biosimilar-to-biosimilar-switching

3. Jeremias S. CMS announces new drug prices under the IRA, including for Stelara and Enbrel. The Center for Biosimilars. August 19, 2024. Accessed January 2, 2024. 

https://www.centerforbiosimilars.com/view/cms-announces-new-drug-prices-under-the-ira-including-for-stelara-and-enbrel

No significant difference in the risk of serious infections between etanercept and infliximab biosimilars and their original brand-name medications was identified.

Etanercept and Infliximab Biosimilars Show No Increased Infection Risk, Comparable Safety

Here are the top 5 biosimilar articles for the week of December 30, 2024. 

 highlight advancements that include FDA guidance to simplify biosimilar interchangeability and CMS drug price negotiations under the Inflation Reduction Act, alongside challenges posed by pharmacy benefit manager rebate practices and the need for more active stakeholder engagement.

top 5 biosimilar conference articles in 2024

 highlight significant progress in the biosimilar landscape, including strategies for market sustainability, safety of switching to biosimilars, and substantial savings through high biosimilar adoption, while also addressing ongoing challenges.

 were granted by the American and European regulatory agencies, including the first interchangeability designations for biosimilars referencing ustekinumab, adalimumab, denosumab, and aflibercept, marking key regulatory milestones in improving patient access to cost-effective treatments.

top legal stories in biosimilars from 2024

 emphasize the ongoing struggle between ensuring timely patient access and addressing challenges like litigation, regulatory hurdles, and patent disputes that shape the competitive landscape of affordable biologics.

: Sarfaraz K. Niazi, PhD, highlights the 

The Top 5 Biosimilar Articles for the Week of December 30

Here are the top 5 biosimilar articles for the week of December 16, 2024. 

 The impact of pharmaceutical companies' 

 on the adoption of trastuzumab biosimilars in the Netherlands led to significant price reductions and increased market share.

 found patient satisfaction was stable after switching from either the reference product or a low-concentration adalimumab biosimilar to the adalimumab biosimilar CT-P17, a high-concentration, citrate-free formulation.

 (Jubbonti/Wyost) has demonstrated analytical, pharmacokinetic, pharmacodynamic, and clinical equivalence to reference denosumab (Prolia/Xgeva), supporting its approval and extrapolation to all approved indications.

 The United States Patent and Trademark Office (USPTO)’s withdrawal of its proposed terminal disclaimer rule is seen as a setback for biosimilar developers, as it preserves patent prosecution practices that favor originator companies and 

increases costs for biosimilar competition

submitted a European marketing application

 for their golimumab biosimilar to treat inflammatory diseases, while Celltrion secured Korean approval for denosumab biosimilars, and Intas Pharmaceuticals partnered with Xbrane Biopharma on a nivolumab biosimilar.

Here are the top 5 biosimilar articles for the week of December 16, 2024.

The Top 5 Biosimilar Articles for the Week of December 16

China's trastuzumab biosimilar market is growing but lags behind European countries, with biosimilars gradually increasing market share and reducing costs despite initial barriers. | Image Credit: diy13 - stock.adobe.com

Despite rapid growth of the biosimilar industry in China, the market uptake of trastuzumab biosimilars in China is lower compared with major European countries, according to a study published in 

High costs of biologics put heavy burdens on worldwide health care systems with the global expenditure reaching $452 billion in 2022. For patients with inflammatory bowel disease, average direct health care expenses are $9000 to $12,000 per person per year in various high-income areas.

 Medication prices in the US typically surpass international costs due to lack of nationwide price regulation, the fragmentation of the health care system, prolonged market exclusivity periods, and confidential rebates negotiated between private insurers and pharmaceutical manufacturers.

It is vital to develop a balance between biomedical innovation and the sustainability of health care systems.

 Biosimilars have the potential to increase payer preferences and market share which led to major price reductions and evidence of a competitive market between 2017 to 2022.

 However, barriers persist, especially surrounding doubt about the safety and efficacy of biosimilars that lead to negative attitudes and unwillingness.

In recent years, the Chinese biosimilar industry has grown but there is limited research on the uptake of biosimilars at the national level. With the approval of the trastuzumab biosimilar, the Chinese market now has access to both individual hospitals and provincial-level administrative divisions (PLADs) to analyze a large sample size.

The study authors looked to provide evidence for promoting the clinical use of biosimilars and improve the accessibility for biological therapy, which would also help other resource-limited countries to address the issue of access to expensive bio-therapy. They conducted the study because "there is a lack of research on the uptake of biosimilars at the national level."

Researchers conducted an analysis based on monthly time series consumption data of trastuzumab in Chinese hospitals on a national scale and applied the interrupted time series regression. The latent class trajectory model (LCTM) was adopted to demonstrate provincial differences and acknowledge potential factors that may alter biosimilar market penetration across PLADs.

On a national level, trastuzumab consumption volume fluctuated upward during the observation period. After the first biosimilar was introduced in July 2021, consumption of originator trastuzumab decreased by 0.5% per month (

= .008) and the growth rate of the overall trastuzumab consumption decreased by 1.1% per month (

 = .014). The national market penetration of biosimilars expressed a moderate increasing trend that reached 27% in February 2023.

Between March 2018 to January 2020, the national consumption of the trastuzumab originator grew at a rate of 2.5% per month (

 < .001). During this period, the overall trastuzumab consumption volume showed an increasing trend, with an average monthly growth rate of 2.5% (

Following the price reduction of trastuzumab originator in January 2020, consumption dropped by 13.1% (

 = .029), accompanied by a 1.9% decrease in growth (

 = .001). In July 2021, the introduction of the first biosimilar brought a decreased growth rate of the originator consumption by 1.1% (

 = .019) with steady decreases by 0.5% per month (

When the price of the originator reduced (

 = .016), the overall consumption of trastuzumab instantly decreased by 14.7%, while the growth rate declined by 1.6% (

 = .005) and maintained a growth rate of 0.9% per month (

The LCTM fit the best when the amount of trajectory classes for biosimilar market penetration rate was 2, leading to 30 PLADs divided into a group demonstrating a faster increase in biosimilar penetration and the other with a slower increase.

There were more PLADs in the fast-increasing group with higher proportions of the population covered by the national basic health insurance but had a lower proportion of the urban population to the total population. There was also a lower proportion of the population covered by the urban employee health insurance program, a lower gross domestic product per capita, a lower total health expenditure per capita, and a lower out-of-pocket expenditure. Overall, national sales volume of trastuzumab emtansine showed average growth, reaching $1 million in September 2021 and fluctuated around $0.9 million.

Study results suggest biosimilars can invoke a transition in treatment from the originator to the biosimilars. The biosimilar market penetration in China is close to several developed countries across Asia and North America. However, uptake remains low in China compared with European countries where market shares show increases over time leading to reductions in expenditures. For instance, the Netherlands experienced significant price reductions and increased market share following the introduction of the trastuzumab biosimilar.

Limitations include a focus on hospital consumption, ultimately neglecting community pharmacies. Additionally, market fluctuations and the brief availability of biosimilars introduced barriers. The study was restricted to a single biological agent and lacked individual case study data for deeper analysis. Future research should consider a broader market perspective and quantitative analysis of competitive agents' influence.

By enhancing comprehension of biosimilars between physicians and patients while implementing provider payment reforms, competition could stimulate and foster market penetration of biosimilars.

“These measures are also meaningful for other resource-limited countries to promote biosimilar uptake and address the issue of access to expensive bio-therapy,” concluded study authors.

1. Wu Q, Wang Z, Fu Y, Luo R, Sun J. Uptake of biosimilars in China: a retrospective analysis of the case of trastuzumab from 2018 to 2023. 

. 2024;9(1):42. doi:10.1186/s41256-024-00372-z

2. Ferreri D. Making the cost of IBD care sustainable. The Center for Biosimilars

. November 2, 2024. Accessed December 16, 2024. 

https://www.centerforbiosimilars.com/view/making-the-cost-of-ibd-care-sustainable

3. Jeremias S. Commercial payer coverage of biosimilars: market share, pricing, and policy shifts. The Center for Biosimilars. December 4, 2024. Accessed December 16, 2024. 

https://www.centerforbiosimilars.com/view/commercial-payer-coverage-of-biosimilars-market-share-pricing-and-policy-shifts

4. Santoro C. Trastuzumab’s evergreening impact on biosimilars, health care costs. The Center for Biosimilars. December 13, 2024. Accessed December 17, 2024. 

https://www.centerforbiosimilars.com/view/trastuzumab-s-evergreening-impact-on-biosimilars-health-care-costs

China's trastuzumab biosimilar market is growing but lags behind European countries, with biosimilars gradually increasing market share and reducing costs despite initial barriers.

China's Biosimilar Market: Trastuzumab Uptake and Future Trends

The impact of pharmaceutical companies' evergreening strategies on the adoption of trastuzumab biosimilars in the Netherlands led to significant price reductions and increased market share. | Image Credit: Valeri Luzina - stock.adobe.com

The introduction of trastuzumab biosimilars in the Netherlands led to significant price reductions and increased market share, despite the evergreening strategy implemented by the pharmaceutical company, according to a study published in 

Major concerns exist regarding the expensive costs of medicines that apply pressure on total health care expenditures, a result of monopoly prices set by pharmaceutical companies since the drugs they manufacture are protected by patents. Original patents are usually valid for 20 years and can extend for an additional 5 years if the development process is lengthier and market authorization is successful.

The "patent dance" is a US legal process designed to streamline patent disputes between biosimilar manufacturers and reference product sponsors.

 It involves exchanging information on patents and their potential infringement, aiming to minimize future legal costs.

Pharmaceutical companies often use "evergreening" to extend drug exclusivity by filing new patents on slightly modified versions.

 This can delay the entry of biosimilars like trastuzumab, potentially leading to societal losses. Assessing the impact of evergreening on biosimilar uptake is crucial.

The study authors set out to explore “the dynamic market share and public health care costs of trastuzumab’s evergreening (subcutaneous) variant during introduction of trastuzumab’s competitive biosimilar variant in the Netherlands.”

Trastuzumab (Herceptin) was approved for the European market by Roche in August 2000 to treat patients with early-stage and metastatic breast cancers. The drug entered the market as an intravenously administered medication that drastically improves survival outcomes for patients with HER2-overexpressing breast cancer.

Trastuzumab is also one of the first biological drugs where the patent expired and an evergreening strategy was applied. The patent for the intravenous trastuzumab expired in 2014, allowing biosimilars to enter the market.

The patent for the subcutaneous administration form remains valid until 2030, limiting the current availability of biosimilars to intravenous trastuzumab.

The study utilized proprietary insurance claim data of all patients who were treated with trastuzumab in Dutch hospitals between January 2013 and December 2020. The average number of treatments per month is 3519.95 with 580.61 average treatments per hospital per year and 4628.97 for all years. About 410.48 mg of trastuzumab and 451.99 mg of the biosimilar were administered per intravenous treatment. The subcutaneous trastuzumab originator has a fixed dosage of 600 mg.

Almost all the participants were women (99.67%) with an average of 56.78 years old. Treatments were given across 73 hospitals in the Netherlands, including 8 academic hospitals, 25 top clinical hospitals, and 40 general hospitals.

The average treatment cycle of a patient consisted of 4.80 treatments of trastuzumab given in combination with chemotherapy whereas 13.16 treatments were given without chemotherapy. There was 33.13% of all intravenous-administered trastuzumab treatments (originator and biosimilars) given in combination with chemotherapy.

An upward trend was identified in the total amount of trastuzumab treatments from January 2013 until January 2014 but then decreases slightly, remaining steady at 3500 treatments per month until June 2018. Following the introduction of biosimilars in 2018, the total use increases until a peak in January 2019. A significant drop in trastuzumab treatments around April 2020 could be attributed to the COVID-19 pandemic.

When the subcutaneous trastuzumab originator was introduced in 2014, it led to a decrease in the use of the intravenous originator and an increase in subcutaneous originators up to a point in 2017 with a 50% to 50% distribution. There was a steep decline in intravenous trastuzumab originator after 2018 when the biosimilars were introduced but it is barely used a few months later. By 2020, biosimilars are used for an estimated 80% of the treatments and subcutaneous trastuzumab originator for 20%.

Hospitals displayed different uptake patterns of both subcutaneous trastuzumab following the introduction in 2014 and biosimilars in 2018. One hospital kept administering subcutaneous trastuzumab for all treatments while others switched using biosimilars for 90% of the treatments. Some hospitals decided not to switch to subcutaneous trastuzumab but replaced intravenous trastuzumab for biosimilars shortly after the introduction. Hospitals also differed in speed in which they switched to subcutaneous trastuzumab and biosimilars.

The study found the introduction of subcutaneous administration form did not change the price level of trastuzumab, whereas the introduction of biosimilars was accompanied by lowering price effects associated with biosimilars. The study also found an increased volume effect after biosimilar introduction, switching decisions made on the hospital level and influenced by patient volume, and health insurer specific effects in the use of subcutaneous trastuzumab.

The financial impact of the evergreening strategy is difficult to determine, potentially limiting study results, and should be interpreted with caution. Additionally, claims data was unable to differentiate between actual costs of administering intravenously or subcutaneously.

Future research is necessary on the impact of pharmaceutical strategies nearing patent expiration on the uptake of biosimilars and the public health care costs. A higher uptake for trastuzumab was recognized in the Dutch market that led to more competitive market structure and significant price drops.

“We recommend a more explicit societal debate to consider if the potential benefits of subcutaneous trastuzumab are worth the additional costs, and at which price it should be reimbursed as the part of the benefit package,” study authors concluded.

1. Kirshner G, Makai P, Brouns C, Timmers L, Kemp R. The impact of an 'evergreening' strategy nearing patent expiration on the uptake of biosimilars and public healthcare costs: a case study on the introduction of a second administration form of trastuzumab in The Netherlands. 

. 2024;25(7):1147-1163. doi:10.1007/s10198-023-01648-w

. November 11, 2024. Accessed December 12, 2024. 

The impact of pharmaceutical companies' evergreening strategies on the adoption of trastuzumab biosimilars in the Netherlands led to significant price reductions and increased market share.