Cameron Santoro is an associate editor for The Center for Biosimilars

Cameron Santoro

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

 written by Vibeke Strand, MD, clinical professor in division of immunology/rheumatology at Stanford University School of Medicine, gave an overview of patient-reported outcomes (PROs) in the VOLTAIRE-RA trial.

 was approved simultaneously in the European Union. In the US, it will launch in February 2025.

 diving into the Association for Accessible Medicines' (AAM) latest report discusses that while generics and biosimilars saved $445 billion in 2023, their potential is hindered by high patient costs, drug shortages, and ineffective policies, underscoring the need for reforms to fully realize their benefits.

approved Celltrion's ustekinumab biosimilar

 for chronic inflammatory diseases, Celltrion expanded access to Zymfentra (subcutaneous infliximab-dyyb) through partnerships with Cigna and Express Scripts, and the Association for Accessible Medicines held a policy briefing addressing barriers to biosimilar adoption.

: The Inflation Reduction Act (IRA) has modestly boosted 

 through Medicare reimbursement, but its impact has been limited due to preexisting competitive market conditions.

To read all of these articles and more, visit 

Videos

The Top 5 Biosimilar Articles for the Week of September 30

Ivo Abraham, PhD, RN.

Ivo Abraham, PhD, RN, director of the Center for Health Outcomes and PharmacoEconomic Research at the University of Arizona Cancer Center, discusses the evolvement of the biosimilar landscape throughout the years in an interview with The Center for Biosimilars®.


Abraham addresses both biosimilars and generics, highlighting their potential to provide more access to patients at lower costs while recognizing the challenges of marketing biosimilars and the need for volume contracts to stay competitive.

This transcript was lightly edited for clarity.

The biosimilar landscape is constantly evolving. What emerging trends in health economics or clinical research do you see impacting the future of biosimilar development and access?

Price erosion is one because it can only go so low. We need to make sure that this does not threaten the biosimilar manufacturing side of the formulary. They have more costs to recover, so there needs to be some way, and it's probably going be more of a coordinated way of limiting the price erosion that we see for the reference products. We know a lot of those costs have already been recouped, whereas a biosimilar company still has to do that. Also, we are seeing the high volume agents that the manufacturer or the reference product is willing to go very, very low in terms of their price because it's made up in part by volume. That's an important aspect.

The other aspect that we need to take into account is we're not going to have influence over which biosimilar you're administered. It's the same thing as with a generic. You can go to the pharmacy and receive a 3-month supply from one company, and 3 months later, it may be another company just because your payer has different contracts or your pharmacy provider.

Dealing with the fact that we're talking about commodity markets, and as we've seen shortages in generic cancer drugs, for instance, manufacturers of generics are pulling out of producing certain treatments because of the margin being so minimal. This is not treating hypertensive patients, where you have millions and millions and millions. Just in the US, you may be talking about a much smaller patient population.

Another thing that is important is that, in the US, we need to let go of our xenophobism, that things that come from abroad are not good. When we talk about biosimilars, we're going to have to take into account that we have now entered also an era of bioparallels. These are products developed somewhere else, are of very high quality, very well researched, with clinical trials and so on, and will enter the US market or are entering the US market at a significant price discount relative to other very well-established products—and I'm referring to PD1 inhibitors—and will provide more access to more patients at potentially lower cost.

What we also need to take into account is that especially the manufacturers of biosimilars that also manufacture generics bundle their products. For instance, have a bundle of chemotherapy agents, not biologic agents, but chemotherapy agents with then a biosimilar of a biological product.

For instance, the first line of breast cancer treatment is highly myelotoxic. Patients are at very high risk of developing neutropenia or febrile neutropenia. Why not, as a manufacturer of generics and biosimilars, create a breast cancer bundle of products? Then the products could be priced accordingly and be sold to payers, providers, and patients.

Ivo Abraham, PhD, RN, University of Arizona Cancer Center, explains how biosimilars are becoming more accessible but face challenges like price erosion and potential shortages.

Future Biosimilar Trends, Challenges, and Opportunities

Here are the top 5 biosimilar articles for the week of September 23, 2024. 

 assessing patient satisfaction with adalimumab for inflammatory bowel disease (IBD) reported a high level of satisfaction with all adalimumab product, including biosimilars.

 with chemotherapy was effective in treating HER2-positive breast cancer, offering high safety and affordability.

: The article by Sarfaraz K. Niazi, PhD, critiques the irrationality surrounding biosimilars, suggesting that 

 in manufacturing could make biosimilars as affordable as generic drugs.

: Savings from generic and biosimilar drugs totaled $445 billion in 2023, showing promise for the growth of both markets and highlighting the success of expansion policies for these products, according to a new report from the 

: Amgen’s Pavblu (aflibercept-ayyh) is the 

 referencing Eylea (aflibercept) to be approved for American patients with retinal diseases.

Here are the top 5 biosimilar articles for the week of September 23, 2024.

The Top 5 Biosimilar Articles for the Week of September 23

Ivo Abraham, PhD, RN. 

Ivo Abraham, PhD, RN, director of the Center for Health Outcomes and PharmacoEconomic Research at the University of Arizona Cancer Center, highlights the challenges and opportunities of biosimilar development and utilization in an interview with The Center for Biosimilars

Abraham suggests innovative risk-sharing models between manufacturers, payers, and providers to incentivize biosimilar development and ensure efficient utilization.

How can innovative risk-sharing models between manufacturers, payers, and providers incentivize biosimilar development and ensure efficient utilization once available?

We first need to ask ourselves, what are the risks of biosimilars? There is always a possibility that there are some extreme cases of a few patients where a biosimilar does not produce the clinical and safety aspects and it can be attributed purely to the biosimilar. So, if a patient has an adverse event or becomes febrile, neutropenic, then we can say it was not because the patients failed to respond to the treatment, that it was something related to the biosimilar. That probability is going to be very, very small, and it's minimal. We have modelled that statistically.

Now, there's the other part of the risk sharing that is important, and that is the financial risks. Their payers and biosimilar manufacturers need to cooperate, and probably need to cooperate on a little bit different model or approach that payers typically cooperate with manufacturers—that is, basically trying to get the lowest price.

We need to take into account that the manufacturer of the reference product is making proportionately a lot more money than the biosimilar company and has the latitude to also come down in price. We can term that 

 but think of it as competing in an increasingly commoditized markets.

The manufacturer of the reference products, we can ask why is it that they make more money proportionately, and it is because they don't have to recoup development costs, regulatory approval costs, legal costs, and so on and so on.

The manufacturer of the reference product to stay competitive has to also lower its price, come in at a lower price, and then either stay the same or minimally increase, but basically, it's a downsloping curve. In terms of the risk sharing, there is clinical risk, which is minimal, but the financial risk is a lot higher for biosimilar companies.

It took many of us by surprise, when suddenly, we saw the announcements—well some of us knew that there was something in the works—of what 

. They're saying they have an interest in using biosimilars as much as possible as a payer, so if they can also cut out more of the middle people, they can help some biosimilar manufacturers, work with them and help them with their developments and then have some kind of an agreement and then that becomes our biologic. Perhaps, this could even lead to the development of a new version of a particular biologic.

In the risk sharing, we see a lot more happening inside the house of the payer, as opposed to everybody sitting around the table and speaking on how to handle risk sharing. The risk is financial as opposed to in other treatment areas or newer treatment areas, where the risk is also clinical—for instance, a new monoclonal antibody that gets approved.

Ivo Abraham, PhD, RN, University of Arizona Cancer Center, analyzes the need for innovative risk-sharing models to promote biosimilar development and utilization.

The Role of Risk-Sharing Models in Biosimilar Adoption

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

 (aflibercept).1 The new product is approved for the treatment of retinal conditions, including neovascular age-related macular degeneration (wet AMD), macular edema following retinal vein occlusion, diabetic macular edema, and diabetic retinopathy.

 Switching children with juvenile idiopathic arthritis (JIA) from anti–tumor necrosis factor originators to biosimilars showed 

similar disease activity and drug persistence

, with good tolerability, supporting the safety and effectiveness of non-medical switching.

 a 9% revenue increase in the first half of 2024, with over €2 billion in sales, driven in part by biosimilar successes and new product launches.

A study found patients with neovascular age-related macular degeneration (nAMD) 

 from aflibercept to the biosimilar ranibizumab, despite fluid challenges.

 While biosimilars could potentially lower costs and improve access to gene therapies, 

 in regulation, manufacturing, intellectual property, and market size pose challenges to their development and market entry.

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

The Top 5 Biosimilar Articles for the Week of September 16

The combination of trastuzumab biosimilar and pertuzumab with chemotherapy was effective in treating HER2-positive breast cancer, offering high safety and affordability.

Trastuzumab biosimilar (Zercepac) and pertuzumab (Perjeta) combined with chemotherapy regimens showed efficacy among patients with HER2-positive 

HER2-positive breast cancer accounts for about 15% to 25% of all molecular subtypes. Common forms of neoadjuvant therapy for this cancer include targeted medications combined with chemotherapy, whereas adjuvant therapies are often forms of surgery.

The European Medicines Agency (EMA) approved the trastuzumab biosimilar in 2020 after a series of comparative quality, preclinical, and clinical studies confirmed its similar efficacy and safety to the reference product.

The trastuzumab biosimilar is administered through an intravenous drip into a vein for over 90 minutes either once a week or once every 3 weeks for patients with breast cancer.

 Typically, patients endure treatment for a year or until the disease returns. However, treatment for metastatic breast cancer continues for as long as necessary.

The EMA approved pertuzumab for combination use with trastuzumab and docetaxel for adult patients with HER2-positive metastatic or locally recurrent unresectable breast cancer in 2013.

Pertuzumab is infused into the vein at a recommended first dose of 840 mg over 60 minutes, followed by a 420 mg dose every 3 weeks, with each dose administered over half an hour to 1 hour.

Researchers aimed to conduct a single-arm real-world study to evaluate the efficacy and safety of trastuzumab biosimilar and pertuzumab combined with other chemotherapy regimens for patients with HER2-positive early or locally advanced breast cancer.

 The primary endpoint was the total pathological complete response (CR), and secondary endpoints were breast pathological CR, objective response rate (ORR), and disease control rate (DCR).

Participants included 22 female patients with HER2-positive breast cancer who received neoadjuvant therapy with a trastuzumab biosimilar and pertuzumab combined with chemotherapy, followed by surgery after 4 to 8 cycles of treatment. Breast cancer was in the left breast of 14 patients and right breast of 8 patients.

Variations of surgery included modified radical surgery (n = 7), mastectomy with sentinel lymph node biopsy (n = 6), and breast-conserving surgery (n = 9). Pathological evaluations found 15 patients achieved CR while 7 patients reached PR; 3 patients displayed CR in the primary breast lesion but had residual tumor cells in lymph nodes.

The study cohort had a breast pathological CR of 81.8%, a total pathological CR of 68.2%, and a breast retention rate of 40.9%. The combination of trastuzumab biosimilar and pertuzumab was comparable to the originator trastuzumab drug (Herceptin) at a 440 mg dose.

The study had a 100% ORR and DCR, meaning all patients achieved these efficacy end points.Most patients received the TCbHP regimen, a combination of 75 mg/m2 docetaxel and 6 mg/mL/min of carboplatin.

 The other patients received the THP regimen (docetaxel, trastuzumab, and pertuzumab) or EC sequential THP (epirubicin and cyclophosphamide combined with THP).

The study was limited due to the small sample size. However, its findings indicate that trastuzumab biosimilar and pertuzumab targeted treatment is effective among patients with HER2-positive breast cancer and offers high safety at low costs. Further research is required to support these findings, which could support the utilization of trastuzumab biosimilar in clinical practice.

Bao YF, Yang JZ, Li XF, Zhu JJ. Real-world clinical study of trastuzumab biosimilar (Zercepac) and pertuzumab (Perjeta) in combination with chemotherapy for neoadjuvant treatment of HER-2-positive breast cancer. 

. 2024;47(7):3225-3228. doi:10.1016/j.asjsur.2024.03.063

Burstein HJ, Hayes DF, Vora SR. Patient education: treatment of early HER2-positive breast cancer (beyond the basics). UpToDate. October 12, 2022. Accessed September 16, 2024. 

https://www.uptodate.com/contents/treatment-of-early-her2-positive-breast-cancer-beyond-the-basics/print

Henlius and Accord Healthcare receive EMA approval for Zercepac, trastuzumab biosimilar. News release. Henlius. July 29, 2020. Accessed September 16, 2024. 

https://www.henlius.com/en/NewsDetails-2670-26.html#:~:text=The%20approval%20was%20based%20on

‌Zercepac. European Medicines Agency (EMA). July 28, 2020. Accessed September 16, 2024. 

https://www.ema.europa.eu/en/medicines/human/EPAR/zercepac#:~:text=It%20is%20given%20by%20infusion

Boix-Perales H, Borregaard J, Jensen KB, et al. The European Medicines Agency Review of Pertuzumab for the treatment of adult patients with HER2-positive metastatic or locally recurrent unresectable breast cancer: summary of the scientific assessment of the committee for medicinal products for human use. 

. 2014;19(7):766-773. doi:10.1634/theoncologist.2013-0348

‌Perjeta. European Medicines Agency. September 17, 2018. Accessed September 16, 2024. 

https://www.ema.europa.eu/en/medicines/human/EPAR/perjeta

Lv M, Guo H, Wang C, et al. Neoadjuvant docetaxel with or without carboplatin plus dual HER2 blockade for HER2-positive breast cancer: a retrospective multi-center Chinese study. 

. 2020;9(6):2079-2090. doi:10.21037/gs-20-791

‌EC chemotherapy. Breast Cancer Now. Accessed September 16, 2024. 

https://breastcancernow.org/about-breast-cancer/treatment/chemotherapy/chemotherapy-drugs/ec-chemotherapy/

Articles

The combination of trastuzumab biosimilar and pertuzumab with chemotherapy was effective in treating HER2-positive breast cancer, offering high safety and affordability. 

Trastuzumab Biosimilar and Pertuzumab Effective, Safe in Neoadjuvant Breast Cancer Therapy

The Top 5 Biosimilar Articles for the Week of September 9

 on post-approval changes for biosimilars, emphasizing the processes for reporting modifications, comparability assessments, and the potential for biosimilars to introduce new indications or formulation changes, which could significantly impact their market competitiveness and accessibility.

 from 63 countries and found that adalimumab and infliximab biosimilars, primarily chosen for their lower cost, are widely available and have improved access to biologic treatment in inflammatory bowel disease (IBD).

switched from the etanercept originator to a biosimilar

 exhibited similar disease activity and drug persistence compared with those who remained on the originator, indicating that nonmedical switching does not negatively impact treatment outcomes.

 that although biosimilars have led to significant price reductions, originator products with sole preferred coverage strategies have maintained market share, suggesting that increased biosimilar uptake alone may not fully leverage the market's competitive and cost-saving potential.

 and specialty drugs, the impact of the Inflation Reduction Act on drug pricing, and the evolving role of pharmacy benefit managers in the market.

Here are the top 5 biosimilar articles for the week of September 9, 2024. 

A study foundpatients with neovascular age-related macular degeneration (nAMD) successfully switched from aflibercept to the biosimilar ranibizumab, despite fluid challenges. | Image Credit: MQ-Illustrations - stock.adobe.com

Patients with neovascular age-related macular degeneration (nAMD) demonstrated maintained visual acuity and macular anatomy when switching from intravitreal aflibercept to biosimilar ranibizumab, but some challenges in fluid management persisted, according to a study published in 

Both AMD and nAMD are common among the elderly population, and cases have increased over the years. Treatment for AMD was revolutionized with the development of anti-vascular endothelial growth factor (VEGF) therapy, which inhibits the growth of abnormal blood vessels in the retina while reducing fluid leakage. Anti-VEGF drugs include bevacizumab, ranibizumab, aflibercept, brolucizumab, and faricimab, which typically come athigh costs, creating access barriers for most patients.

“The advent of anti-VEGF therapy has been a game-changer in the management of this condition, particularly wet AMD. However, the high costs of these drugs remain a challenge,” the authors wrote. "Biosimilar anti-VEGF agents offer a promising solution to this problem, potentially making effective AMD treatment accessible to more patients and easing the financial burden on the health care system. Therefore, they have the potential to play a crucial role in the future landscape of AMD treatment.”

Biosimilar anti-VEGF agents were created with the intention of lowering drug costs while offering lifesaving drugs at an affordable, accessible rate. Some patent expirations have led to reduced biosimilar drug costs while further facilitating the approval and adoption of various other biosimilar treatments.

 In places like Singapore, Denmark, and Sweden, biosimilar promotion has led to quicker adoption through analysis of the cost benefits.

Researchers aim for similar cost savings to be emulated globally through biosimilar manufacturing. Biosimilar development has prompted market growth among major drug companies, offering potential cost savings and profit.

The new study aimed to determine how eyes with nAMD respond to the switch from aflibercept to the biosimilar ranibizumab, as data in this area are lacking, according to the study authors.

The multicenter, retrospective, observational study was led in a group of eye hospitals in eastern India with participants who were 50 years or older with baseline visual acuity of 20/40 or worse. The primary outcome measure was the change in best corrected visual acuity (BCVA) before and after switching. Changes in central macular thickness (CMT) from baseline to follow-up at 12 months were measured as secondary outcomes.

A total of 29 patients were included in the study, with a median age of 72.55 years. The study population had slightly more female (58.6%) than male (41.4%) participants. The mean visual acuity improved from baseline (55 ± 10.2) to the switch (70 ± 8.5). By the 12-month final follow-up, the mean visual acuity was 62.3 ±8.9.,There was an improvement of around 7.6 Early Treatment Diabetic Retinopathy Study letters in visual acuity from baseline.

The analysis revealed a positive association between higher initial visual acuity and subsequent visual acuity outcomes. Although noninferiority to the switch was not demonstrated at the final follow-up, there was a significant improvement in overall visual acuity.

There was a significant decrease in average CMT from baseline (400 ± 50 mm) to the switch (290 ± 45 mm). This reduction persisted throughout the 12-month follow-up period, with a final CMT of 280 ± 40 mm. The consistent changes in CMT over time were statistically significant(P< .01).

The proportion of patients with subretinal fluid (SRF) decreased significantly to 17.24% from the time of switching to biosimilar ranibizumab. Follow-ups that occurred after switching to the biosimilar ranibizumab showed a moderate increase in the presence of SRF, reaching 44.83% after 12 months. Similarly, 55.17% of patients had intraretinal fluid at baseline but decreased from aflibercept to 6.9% at the time of switching, indicating an effective response to the original treatment.

There was a strong, positive correlation between patient age and the total number of injections received, indicating that older patients tended to receive more injections.

No serious adverse events (AEs) were found during the initial phase of aflibercept treatment or subsequent treatment with the biosimilar ranibizumab. However, it is important to note that it is difficult to make definite assumptions on AEs due to the small number of participants.

Study limitations include the retrospective design, small sample size, brief follow-up period, lack of control group, and the use of the PRN regimen. Additionally, the study was not powered for safety analysis, and AEs could have been underreported because the study was based on medical chart analysis, the authors noted.

Regardless of study limitations, the research provides insight into the potential of biosimilar anti-VEGF therapy to offer more accessible and affordable treatment options, especially among patients with financial or insurance restrictions.

“Biosimilar anti-VEGF agents offer a promising solution to this problem, potentially making effective AMD treatment accessible to more patients and easing the financial burden on the health care system,” the study authors concluded.

Chakraborty D, Boral S, Sinha TK, et al. Transitioning from aflibercept to biosimilar ranibizumab in neovascular AMD (The TRANSFORM Trial): amulticenter observational study. Clin Ophthalmol. 2024;18:1819-1828. doi:10.2147/OPTH.S459085

Jeremias S. Singapore experience shows benefit of value-driven strategies in generating biosimilar savings.The Center for Biosimilars®. July 30, 2024. Accessed September 5, 2024. 

https://www.centerforbiosimilars.com/view/singapore-experience-shows-benefits-of-value-driven-strategies-in-generating-biosimilar-savings

Sharma A, Reddy P, Kuppermann BD, Bandello F, Lowenstein A. Biosimilars in ophthalmology: "Is there a big change on the horizon?". Clin Ophthalmol. 2018;12:2137-2143. doi:10.2147/OPTH.S180393

A study found patients with neovascular age-related macular degeneration (nAMD) successfully switched from aflibercept to the biosimilar ranibizumab, despite fluid challenges.

Patients With nAMD Successfully Switch From Aflibercept to Ranibizumab

Ivo Abraham, PhD, RN, director of the Center for Health Outcomes and PharmacoEconomic Research at the University of Arizona Cancer Center, offered insight on how to effectively engage with patient advocacy groups to address concerns regarding biosimilars in an interview with The Center for Biosimilars®.


Abraham suggests combining information for patient advocacy organizations so they are educated on certain drugs and drug classes because this will promote a greater awareness about biosimilars.


Patients often have concerns regarding biosimilars. How can we effectively engage patient advocacy groups to address these concerns and promote informed decision-making?

Well, patient advocacy organizations obviously have an enormous role here. We need to make a distinction here between clinically based patient advocacy organizations—let's say, patient advocacy organizations for leukemia patients—vs more general population advocacy organizations.

The diagnosis- or disease-based patient advocacy organizations are in a dilemma because a good part of their budget comes from the pharmaceutical industry, and that's good that pharma supports that, but it comes with some strings attached.

What if the manufacturer of a reference product or from an originator is one of your great benefactors, has more money to spend, and then you have a midsize—let alone a small—biosimilar company who cannot provide the level of financial support to patient advocacy organizations?

There, I think we need to work with patient advocacy organizations on bundling the information that patients need to know and bundling it in first instance about what a drug or class of drugs does.

Now there's choices and your insurer may make the choice, the decision for you in terms of what is covered. More generally I think we will see greater awareness, we're already seeing it in patient advocacy organizations with regard to biosimilars.

Ivo Abraham, PhD, RN, University of Arizona Cancer Center, urges stakeholders to provide patient advocacy groups with comprehensive information about specific drugs and drug classes to increase patient understanding of biosimilars and promote informed decision-making.

Promoting Informed Decision-Making Through Biosimilar Awareness

The top 5 biosimilar articles for the week of September 2, 2024. 

 comes expense reports, new biosimilar business deals, and insights into how federal policy impacts biosimilar company pursuits.

2023 European Alliance of Associations for Rheumatology (EULAR)

 recommendations for psoriatic arthritis (PsA) provide an evidence-based treatment strategy, prioritizing conventional and biological disease-modifying antirheumatic drugs, including biosimilars, tailored to disease manifestations, with an emphasis on safety, cost-effectiveness, and patient-centered care.

 led to significant price increases for etanercept, resulting in over €3.42 million in excess health care costs, according to a recent study.

urges stakeholders to engage with the FDA on its Reddit forum

—where a representative will answer complex biosimilar questions—encourages clearing misconceptions, and advocates for updates to the Biologics Price Competition and Innovation Act guidelines.

 for the first half of 2024 revealed 29% growth in biosimilar revenue, as well as a 7% increase in net sales, showcasing the value of biosimilars for biopharmaceutical manufacturers.

Here are the top 5 biosimilar articles for the week of September 2, 2024. 