Cameron Santoro is an associate editor for The Center for Biosimilars

Cameron Santoro

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.

To read all of these articles and more, visit 

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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

Articles

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. 

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.


This transcript was lightly edited for clarity.

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]

. The Jubbonti is for Prolia, the Wyost is for Xgeva. One is more oncology based, one is more osteoporosis based.

They were approved, but there's no announcement on when they're going to be launched. We're thinking they might even be delayed in launch till 2025.

With only one manufacturer coming out, Sandoz, with both of those, we'll get some discount on the brand and reference drug but it's not going to be significant. It's not going to be like the 

Humira [adalimumab] situation with 9 or 10 biosimilars.

What are your thoughts on what the launch of the first tocilizumab biosimilar means for patients with autoimmune conditions?

 is actually IV [intravenous] and sub-q [subcutaneous]. I think that the 2 products launched, 

 is both IV and sub-q, and that's from Fresenius Kabi.

For the most part, Actemra is used in rheumatoid arthritis, a couple other conditions as well. Getting biosimilars in a different therapeutic area, including Actemra, that will be a big advancement. That's 2 biosimilars, so we will get a little competition there on pricing, but I don't know if I can predict what the discounts will be—maybe, 20% to 30% off.

How are pharmacy and therapeutics committees likely to approach new pipeline drugs, considering factors like efficacy, safety data, and potential cost compared to existing options?

P&T [pharmacy and therapeutic] committees are pretty standard in their approach on how they review drugs for formulary inclusion. It really comes down to safety, cost, and efficacy.

I think in today's world, the only difference is that there's a lot of these new orphan drugs which don't have a lot of competitors, so the P&T committees have to look at a drug on its own or a small number of patients, so they really look at the efficacy opportunity—which patients should get the drug, and what the criteria can be.

It's a lot less managing 4 or 5 drugs in a therapeutic area and comparing the pros and cons of drugs that are very similar. Nowadays, we're comparing a million-dollar drug which has no competition and who the patient should be and what the criteria should be. So there is a little shift in reviewing drugs from multiple drugs in 1 therapeutic class to orphan drugs.

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.

Upcoming Biosimilars and the Impact of IRA: Key Takeaways From Jeffrey Casberg

This article was originally published by 

Biosimilar uptake in the US has not met the expectations of many health care professionals who believe 

 can lead to reduced spending, according to a study published in 

As prices have increased for biologic drugs, these medications made up 46% of US prescription drug spending in 2022, despite only making up 3% of prescriptions. Originally, the assumption about biosimilars was they would help lower costs and improve patient access to biologic therapies through market competition. However, the first decade following the Biologics Price Competition and Innovation Act of 2009, which established an FDA approval pathway for biosimilars, did not have successful biosimilar competition as policy makers expected. Within the first 2 years, biosimilars had less than 30% of the market share compared with most biologic drugs facing competition.

In 2023 alone, specialty medicines accounted for 54% of spending, an increase from 49% in 2018.

 Market uptake of biosimilars has ranged based on the medication, from 8% for insulin lispro to 82% for bevacizumab. By the end of last year, adalimumab biosimilars accounted for 2% of volume, likely due to contracts the originator products are under and the differences in biosimilar formulations.

Economic factors that hinder biosimilar uptake in the US include the absence of financial rebates for biosimilars, leaving payers disinterested in supporting biosimilars.

 Additional factors like access to health insurance, clinics, and transportation can also hinder biosimilars.

The study found several patient factors that were independently associated with higher odds of initiating a biosimilar. | Image credit: Kiattisak - stock.adobe.com

Noneconomic factors, such as complex naming conventions, health care provider knowledge gaps, and safety concerns, have hindered biosimilar uptake in the US. Despite these challenges, global studies demonstrate increased patient access and treatment options through biosimilar utilization.

“The reasons for slow biosimilar uptake remain unclear,” the authors of the new study wrote.

 “Existing studies have suggested that there may be important variation in biosimilar initiation across patient characteristics and sites of care, but these studies have been limited in terms of the number and types of biosimilars investigated.”

Their study aimed to provide a better understanding of the reasons for inadequate biosimilar uptake in the US by analyzing characteristics of patients and prescribers initiating biosimilars for 7 biologic drugs from 2013-2022.

The cross-sectional study began on November 1, 2013, when the first biosimilar entered the market, and ended on March 31, 2022. Patients initiated 1 of 7 biologic medications—filgrastim, bevacizumab, epoetin alfa, trastuzumab, pegfilgrastim, infliximab, or rituximab—or corresponding biosimilars. The primary outcome was the proportion of patients who initiated the reference biologic or a biosimilar version.

A total of 196,766 patients initiated 1 of the 7 biologics or corresponding biosimilar versions during the study period. Most patients identified as White (69%) and women (58%), with an average age of 68.8 years. Patients were more likely to be enrolled in a Medicare Advantage plan (74%), receive biologic treatment in an office compared with other locations (62%), and have biologic drugs prescribed by a specialist (49%). While uptake varied between drugs, only 27% of patients overall initiated a biosimilar version.

The first biosimilar market entry dates in the US ranged from filgrastim in November 2013 to rituximab in November 2019. Patients who initiated a biosimilar increased from less than 1% in 2013 to 34% in 2022.

In 2022, more than half of patients who initiated filgrastim, trastuzumab, infliximab, rituximab, and epoetin alfa used biosimilar versions. However, less than 30% of patients initiated biosimilar versions of pegfilgrastim and bevacizumab.

Characteristics Associated With Biosimilar Initiation

The study found several patient factors that were independently associated with higher odds of initiating a biosimilar. Patients under 18 years of age were less likely to initiate a biosimilar (adjusted OR [aOR], 0.33) compared with patients 45 to 64 years old (aOR, 1.12). The only significant difference in race and ethnicity was among patients who identified as Black, who were less likely to initiate a biosimilar (aOR, 0.9) compared with patients who identified as White.

Lower odds of biosimilar initiation were associated with treatment in physician offices compared with hospital outpatient settings (aOR, 0.65). Patients who were prescribed biologics by a primary care clinician were more likely to initiate a biosimilar version compared with biologics prescribed by a specialist (aOR, 1.17). Regarding geographic variations, the highest rates of biosimilar initiation were seen in the Southern region (aOR, 1.26) and the West (aOR, 1.36) compared with the Northeast.

Initiation also varied among the 7 drugs and was associated with patient and prescriber characteristics. Patients under 18 years old were less likely than patients 65 years or older to initiate biosimilars for all drugs, except pegfilgrastim (aOR, 3.94). The study excluded 77% of the bevacizumab initiators with ophthalmologic diagnoses, and the overall number of patients initiating biosimilars increased from 27% to 37%.

Study limitations included reliance on biologic and biosimilar initiators, limited racial and ethnic data, and exclusion of other potential uptake factors. Future research should consider these factors to improve generalizability.

“Biosimilar uptake among new users has been less robust than expected in the US,” the authors concluded. “We identified that biosimilar initiation varied by patient age, insurance type, geography, and site of care, and by prescriber specialty. Targeted policy solutions to increase biosimilar uptake could result in substantial savings to patients and the health care system.”

1. Hong D, Kesselheim AS, Ameet Sarpatwari, Rome BN. Biosimilar uptake in the US: patient and prescriber factors. 

. 2024;43(8):1159-1164. doi:10.1377/hlthaff.2023.01215

2. Jeremias S. Overcoming economic, noneconomic barriers to biosimilar adoption in oncology. The Center for Biosimilars

 June 20, 2024. Accessed August 13, 2024. 

https://www.centerforbiosimilars.com/view/overcoming-economic-noneconomic-barriers-to-biosimilar-adoption-in-oncology

3. Jeremias S. Biosimilars account for 23% market share, with wide uptake disparities across molecules. The Center for Biosimilars. May 22, 2024. Accessed August 13, 2024. 

https://www.centerforbiosimilars.com/view/biosimilars-account-for-23-market-share-with-wide-uptake-disparities-across-molecules

Delayed biosimilar uptake in the US is driven by payer, provider, and patient barriers, but targeted interventions can help boost utilization and savings.

Biosimilar Uptake Lags in US Despite Potential Cost Savings

The Top 5 Biosimilar Articles for the Week of August 19

 Patients with diabetic macular edema (DME) 

 when treated with biosimilar candidate CT-P42 or reference aflibercept (Eylea) in terms of efficacy, with similar pharmacokinetic (PK), usability, safety, and immunogenicity profiles.

 for 10 drugs under the Inflation Reduction Act (IRA), sparking mixed reactions, with concerns that including drugs facing imminent biosimilar competition could hinder market access to lower-cost alternatives.

 Celltrion's adalimumab-aaty biosimilar is 

 for all Costco members, while Amgen sues Samsung Bioepis over the latter’s denosumab biosimilar candidate, and GlycoNex progresses its denosumab biosimilar SPD8 to phase 3 trials.

 for the first 6 months of 2024, a 10-fold increase from the same period the year prior. The new figures come after the company received its first 2 FDA approvals in 2024.

 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.

Here are the top 5 biosimilar articles for the week of August 26, 2024.

The Top 5 Biosimilar Articles for the Week of August 26

Strategies for Effective Biosimilar Education, Adoption

Ivo Abraham, PhD, RN, director of the Center for Health Outcomes and PharmacoEconomic Research at the University of Arizona Cancer Center discussed educational tools that could help physicians overcome biosimilar adoption hesitancy, in an interview with The Center for Biosimilars

Abraham cites instances of successful, collaborative educational approaches and emphasizes their importance for targeted learning. However, he cautions that concerns about biosimilars, rooted in fear, may persist as an obstacle.

This transcript was lightly edited for clarity. 

Physician knowledge and acceptance are crucial for biosimilar adoption. What targeted education strategies can we implement to overcome potential physician hesitancy towards biosimilars?

The reality is that today, 2024, most clinicians, and I think it goes beyond physicians, it also includes clinical pharmacists, nurses, have perhaps not accepted, but are dealing with the reality of biosimilars and the fact that they're here to stay and the payers will decide whether biosimilars and the extent to which biosimilars are adopted.

We need to look at models, not just education, but at models of good collaboration. For instance, what 

 has done, basically he sat down, I've heard him tell the story. He sat down with the medical staff and put together a model of clinical pharmacists, nurses, and physicians working together.

Yes, there will always be still some lingering reluctance or fear mongering. I think in part that is a generational issue. I would say that most clinicians now in cancer care, immunology, or immune related diseases, are very familiar with the reality of biosimilars.

It's not a matter of really advocating further, those who are going to dig in their heels are going to dig in their heels, but they're going to be overrode because prior authorization will not be granted if you are not within the formulary. The payers are for better or for worse, the key driver here.

Ivo Abraham, PhD, RN, University of Arizona Cancer Center, suggests implementing targeted educational strategies to overcome physician hesitancy towards biosimilar adoption.

 for the first half of 2024 amounted to €26.9 million ($29.4 million), showing a strong start to the year, according to the biosimilar developer’s earnings report.

An analysis of subcutaneous biosimilar and originator tumor necrosis factor (TNF) inhibitors for rheumatic diseases found 

no significant differences in survival or discontinuation

Here are the top 5 biosimilar articles for the week of August 19, 2024.