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 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.

To read all of these articles and more, visit 

Videos

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.

This transcript was lightly edited for clarity.

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. 

The Top 5 Biosimilar Articles for the Week of September 2

Patients with rheumatoid arthritis (RA) who switched from the etanercept originator to a biosimilar had similar disease activity and drug persistence as those who remained on the originator, indicating that nonmedical switching does not negatively impact treatment outcomes, according to a Danish study.

, investigated clinical outcomes associated with switching between etanercept products. Patients were monitored for changes in 28-joint disease activity scores (DAS28) at 6 and 12 months.

Although FDA and European Medicines Agency approval of a biosimilar confirms the safety and efficacy of the product in comparison with its originator in a particular patient population, switching studies can provide additional context into the safety of moving a patient off of the originator and putting them on a biosimilar. | Image credit: AI generated using Dall-E3

Reference etanercept, marketed as Enbrel, has been on the European market since 2000, making it one of the first tumor necrosis (TNF) inhibitors to be approved in the European Union for the treatment of RA.

 The prevalence percentages of RA in the US and Northern European countries are typically higher than the worldwide prevalence percentage (0.5%-1.0% vs 0.24%).

 The annual incidence of RA in the US and Northern Europe is estimated to be about 40 per 100,000 persons.

After the patent for the Enbrel expired in 2015, biosimilar versions were introduced, leading to many patients being switched from the originator to the biosimilar for cost-saving reasons. While small studies on other TNF inhibitors have shown mixed results regarding treatment discontinuation and the nocebo effect, there is limited research comparing patients who switch from the etanercept originator to a biosimilar with those who do not. The present analysis aimed to address this gap by investigating drug survival and disease activity in RA patients after switching from the originator to the biosimilar.

The study was conducted using data from the British Society for Rheumatology Biologics Register for RA (BSRBR-RA), an observational prospective cohort that tracks patients with RA who start biologic or targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs).

Patients were matched based on factors such as gender, age, and disease duration. Data on disease activity and drug persistence were collected at the time of switching, as well as 6 and 12 months afterward. Statistical methods were used to assess drug survival, while logistic regression and multiple imputation were employed to analyze changes in disease activity. Sensitivity analyses were also conducted to ensure the robustness of the findings.

In this study, 1024 patients who switched from etanercept originator to a biosimilar were matched 1:1 with patients who remained on the originator. At the point of switching (or the index date for the originator cohort), both groups were similar in age (median, 64 years), gender (female, 76%), and disease duration (median, 19 years). Most patients (71% in the biosimilar cohort and 69% in the originator cohort) had initiated etanercept as their first-line b/tsDMARD therapy. The median time on the originator before switching was 9.3 years for the biosimilar cohort and 9.6 years for the originator cohort. The biosimilar group had a slightly longer median follow-up after the switch (2.7 years) compared to the originator group (2.2 years).

Kaplan-Meier estimates showed that 81% of biosimilar patients and 84% of originator patients remained on treatment after 1 year, 72% and 74% remained on treatment at 2 years, and 65% and 65% remained on treatment at 3 years, respectively. The HR for discontinuation was 1.06 (95% CI, 0.89-1.26), indicating no significant difference between the groups.

In the originator cohort, 326 patients (32%) switched to a biosimilar during the follow-up period, while 205 patients (20%) stopped etanercept treatment altogether. In the biosimilar cohort, 346 patients (34%) discontinued therapy, with 127 of these patients (37%) switching back to the originator, and 95 of them (9% of the entire biosimilar group) doing so within the first year. Most biosimilar patients stopped treatment due to ineffectiveness (n = 161), with 42% switching back to the originator and 55% changing to another b/tsDMARD. Among those who stopped due to adverse events (n = 96), 48% remained off b/tsDMARD therapy at their last follow-up.

For the 505 patients in each cohort with available disease activity data, disease activity at the index date was low and similar across both groups. The median tender joint count was 1, the median C-reactive protein level was 5 mg/L, and the median DAS28 score was 2.9. After 6 months, disease activity remained stable, with no significant differences between the cohorts.

The median DAS28 was 3.1 in the biosimilar group and 2.8 in the originator group, with no median change in DAS28. The proportion of patients in DAS28 remission was 34% in the biosimilar group and 42% in the originator group. At 1 year, the median DAS28 was 2.8 for the biosimilar cohort and 3.0 for the originator cohort, with 42% and 38% in remission, respectively. Additionally, 36% of the biosimilar patients and 31% of the originator cohort experienced an improvement in DAS28 by more than 0.6 units.

Similar results were observed when the analysis was restricted to patients who started etanercept as their first b/tsDMARD therapy.

1. Kearsley-Fleet L, Rokad A, Tsoi M-F, et al. Outcomes following switching from etanercept originator to etanercept biosimilar in 1024 patients with RA: a matched-analysis of the BSRBR-RA. 

. 2024;63(8):2082-2092. doi:10.1093/rheumatology/kead470

2. Hassett B, Singh E, Mahgoub E, O’Brien J, Vicik SM, Fitzpatrick B. Manufacturing history of etanercept (Enbrel): consistency of product quality through major process revisions. 

. 2018;10(1):159-165. doi:10.1080/19420862.2017.1388483

3. England BR, Mikuls TR. Epidemiology of, risk factors for, and possible causes of rheumatoid arthritis. UpToDate. Updated February 19, 2024. Accessed August 20, 2024. 

https://www.uptodate.com/contents/epidemiology-of-risk-factors-for-and-possible-causes-of-rheumatoid-arthritis#:~:text=Estimates%20of%20RA%20prevalence%20in,persons%20%5B2%2C4%5D

Patients with rheumatoid arthritis who 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.

Switching From Originator Etanercept to Biosimilar Version Proves Safe, Effective in RA

In an interview with The Center for Biosimilars

, Jeffrey Casberg, senior vice president of pharmacy at IPD Analytics, discussed key products facing upcoming generic and biosimilar competition. He highlighted the importance of monitoring ustekinumab biosimilars, which are set to launch in early 2025, and aflibercept biosimilars, which may be delayed until 2025 or later. Casberg also addressed the impact of the Inflation Reduction Act (IRA) and pharmacy benefit manager (PBM) legislation on drug pricing, predicting increased transparency and changes in benefit designs.

He touched on the potential of value-based pricing models, suggesting they may offer opportunities, particularly for high-cost therapies, but are unlikely to become the dominant pricing strategy. Casberg identified three promising specialty drugs: donanemab for Alzheimer disease, resmetirom for nonalcoholic steatohepatitis, and Winrevair for pulmonary arterial hypertension.

Regarding the FDA approval of denosumab and tocilizumab biosimilars, Casberg noted their potential impact but cautioned that pricing competition might be limited due to the small number of manufacturers. Finally, he observed that pharmacy and therapeutics committees are now focusing more on orphan drugs, given their unique challenges in efficacy, safety, and cost evaluation.

With brand patents expiring, which products about to face upcoming generic and biosimilar competition do you think stakeholders should be keeping their eye on?

Yeah, there are a couple products coming down the road that would be losing exclusivity. The first one I'll hit is 

 [liraglutide], it's a GLP-1 [inhibitor]. You can't talk about pharmaceuticals today without talking about GLP-1 [inhibitors] and weight loss.

So, Victoza was kind of a big advance back in its day. It was the first once daily GLP-1 [inhibitor], once daily subcutaneous administered injectable product. It has less nausea associated with it than its previous predecessor, 

 [exenatide]. It was also the first GLP-1 [inhibitor] that had cardiovascular positive studies for cardiovascular effect. Great drug but I don't see it really helping with this whole GLP-1 [inhibitor] shortage and weight loss issue.

 [dulaglutide], they both have about 50% the weight loss that 

 [tirzepatide] have so I don't see all of a sudden a big rush to go to Victoza generic because number 1: it's once a day, and number 2: it doesn't have the weight loss that some of the big products that you're hearing about every day have. So, that's Victoza, that'll be coming shortly here in June. I think there could be quite a few generics.

 [dasatinib]. They're both tyrosine kinase inhibitors similar to 

 [imatinib mesylate], great drugs in oncology, pretty expensive therapies, and we should get quite a few generics and a good amount of price reduction there.

Then moving over to the biosimilars side, 

 [ustekinumab] biosimilars are coming. Everybody's been talking about 

 [adalimumab] and 9 or 10 companies bringing those [biosimilars] to market but almost just as big, Stelara is a big drug—$15 to $20 billion product—and it also has 8 or 9 manufacturers lined up to bring products to market. We'll have to see if the adoption by payers is similar or quicker, we're just starting to have some success and conversion of Humira to biosimilars. We'll have to see how the payers adopts Stelara [biosimilars]. Maybe they've gained some more confidence and learned a little bit from the Humira introduction. We'll have to see and Stelara will be coming early in 2025. Amgen has the first product out but then pretty quickly thereafter, several other products will hit.

 [aflibercept] biosimilars in the ophthalmology area, for age-related macular degeneration. We had 

 [ranibizumab] biosimilars come out with a couple of biosimilars recently and those biosimilars have done pretty well.

Eylea, we're watching, we don't know if it's going to come out this year, or in a year or 2. There's an opportunity this year, but IPD, the company I work for does a lot of predicting of this and we think it actually may not be in 2024, it might be 2025 or 2026 before we get Eylea, but watch for that. I had mentioned Victoza, Trulicity is a $16 billion GLP-1 [inhibitor], and it's biosimilar [could be] out in 2027. Something to plan for by the payers.

Do you foresee any policy changes or market forces that could significantly alter the cost landscape for both branded and generic drugs in the near future?

So policy or legislation, everything is about politics. I guess I'll mention 2 things. I'll mention the 

. Those would be the 2 hot ones on the IRA side, we just had the first release of the negotiated drugs and which drugs they are. We'll be getting 

, a new acronym for drug pricing, those will be announced coming up soon.

We're going to have the out-of-pocket cost of Part D reduced to the max of an out-of-pocket cost to $2,000. That's big for patients, impactful to manufacturers, and payers. Now they're going to have to deal with different benefit designs and how they're going to market the drug and price the drug or how payers are going to make the benefits work with the new $2,000 max, so there is something for everybody there.

Then 2025 redesign, for the Inflation Reduction Act, there's also quite a few different benefit designs changing for 2025. There's 

 so the manufacturers have to watch how much they're raising the prices of their drugs. If they go up too high, too quickly, then they get these penalties against them. The IRA has a number of different things, pretty complex, and everybody's paying attention to that.

Then on the second hand, it would be PBM legislation. I guess it depends on who you are and your feeling towards PBM legislation. I think it probably just comes down to more transparency. Every business has to make money and PBMs have done it. Somebody could argue they did it okay. Some say it was all smoke and mirrors but I think there's legislation now to have more transparency on PBMs. We'll see how that rolls out but a lot of discussion up in Washington on that these days.

Value-based pricing models are increasingly being explored. How do you think value-based pricing will impact the development, approval, and access to new drugs?

So value-based pricing, you hear a lot about it. You hear people trying to implement it, manufacturers bring proposals to payers on value-based pricing models. What we don't hear of are the results and if they are working or not.

I don't know in the long run, if value-based pricing will be the 'be all and end all' and change the way drugs are paid for in the United States. I'm going to say no but I think there's some value to value-based pricing and in how you look at drugs and evaluate them.

I think especially some of these high cost therapies have opportunities for some value-based models. As I was saying earlier, there's more and more of these high cost, really expensive products and looking at outcomes and measuring outcomes, that kind of thing are for these gene therapies and other expensive therapies.

I'm not saying value-based pricing will take over but I think there's opportunity in the future for use of them.

In your view, what are the top 3 promising specialty drugs currently coming down the pipeline and why should stakeholders be keeping an eye on them?

The first one I'll talk about is donanemab for Alzheimer's disease by 

; it's an amyloid-β inhibitor for early Alzheimer's disease. It would be a little bit different than 

 from Biogen, which was fully approved more recently.

Donanemab was originally going to be approved beginning of 2023, so over a year ago, but it has had a little bit of a storied pathway to approval. We were watching for an approval here any day during this last month or so, then out of the blue, there was an announcement that the FDA has requested an 

If I'm a manufacturer, not really happy about that; you never really want extra scrutiny on your drug. I'm sure they're going to talk about the dosing regimen, the potential for shorter duration of therapy compared to Leqembi probably the ARIA [amyloid-related imaging abnormalities] side effect profile. They haven't given us a date for that FDA Advisory Committee meeting. I would anticipate a date being announced any day and I still think there's opportunity for approval before the end of 2024.

I think one of the other products that is exciting is resmetirom, or Rezdiffra. for NASH [nonalcoholic steatohepatitis]. First product approved for NASH. Again, a therapeutic area we've been waiting for therapies now for maybe 10 years. Finally we do have an approval. Congratulations to 

 on that, getting their product over the finish line.

A once daily, oral product. It showed signs of efficacy and NASH resolution and fibrosis improvement. Prescribing information did not include discussion of the need for biopsy in diagnosis. So, to diagnose NASH, now called MASH [metabolic dysfunction-associated steatohepatitis], the gold standard is liver biopsy, but that's pretty invasive. You can also use noninvasive therapy testing to get diagnosis of staging of NASH in the liver. They did not have that, which was a plus for Madrigal.

It would be interesting to see how the payers set up their criteria for approval. There's a whole lot of population out there that could be treated with this, so that's another big approval that just occurred.

I'll just mention one other recent approval. It's called 

 for pulmonary arterial hypertension, sotatercept, by Merck. Winrevair is the brand name.

It's a new product for PAH, pulmonary arterial hypertension. It's a new mechanism of action, and has the potential to be more disease modifying—the other therapies out there are more symptomatic treatments—and probably early on will be used as add-on or [in the] second or third line. But I think as physicians get used to it, they could move it up in therapy.

It is pretty expensive: $240,000 for most patients, could be $480,000 for some patients. It's a weight-based dosing, so 1 vial or 2 vials. I think it's subcutaneous every 3 weeks, and it can be self-administered or professionally administered.

What is your reaction to the FDA approval of the first denosumab biosimilars?

So denosumab biosimilars, there was 2 approved; 

Wyost [denosumab-bbdz] and Jubbonti [GP2411]

Jeffrey Casberg discusses key upcoming biosimilars and specialty drugs, the impact of the Inflation Reduction Act on drug pricing, and the evolving role of pharmacy benefit managers in the market.