Cameron Santoro is an associate editor for The Center for Biosimilars

Cameron Santoro

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

Articles

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.

To read all of these articles and more, visit 

Videos

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

 rates due to inefficacy or adverse events, with biosimilars showing lower overall discontinuation rates and higher retention rates.

 In an interview, Ha Kung Wong, an intellectual property attorney, explained that the 

Biologics Price Competition and Innovation Act of 2009

 provides a structured but optional "patent dance" for biosimilars, which helps streamline patent disputes, potentially reducing litigation and encouraging early settlements.

, the fourth aflibercept biosimilar to be approved for Americans with age-related macular degeneration and other retinal eye diseases.

 Sarfaraz K. Niazi, PhD, argues that the S-150 bill, also known as the 

"Affordable Prescriptions for Patients Act of 2023,"

 aims to reduce drug prices by addressing anti-competitive practices, such as patent thickets and product hopping, which hinder the entry of cheaper biosimilars and generics into the market.

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

Biosimilar CT-P42 demonstrated comparable efficacy, safety, and tolerability to reference aflibercept in treating diabetic macular edema. | Image Credit: nazif - stock.adobe.com

Patients with diabetic macular edema (DME) displayed similar outcomes when treated with biosimilar candidate CT-P42 or reference aflibercept (Eylea) in terms of efficacy, with similar pharmacokinetic (PK), usability, safety, and immunogenicity profiles, according to a study published in 

Patients with diabetes often develop DME, a serious form of vision loss. The accumulation of extracellular fluid in the macula resulting from DME can lead to increased retinal vasculature permeability secondary to microvascular damage to the inner retinal capillaries and development of retinal microaneurysms.

A critical component to this pathophysiology is vascular endothelial growth factor (VEGF), which alters retinal capillary permeability by increasing the phosphorylation of proteins involved with tight junctions like zonula occludens.

 Endothelial cell proliferation is the aftermath of the VEGF activation of mitogen-activated protein.

Some of the recommended drugs for patients with DME include aflibercept, bevacizumab, faricimab-svoa, ranibizumab, dexamethasone, and fluocinolone acetonide.

 Providers may also suggest procedures like photocoagulation to address the leakage in the eye or vitrectomy to remove scar tissue or cloudy fluids.

Both the FDA and the European Medicines Agency (EMA) approved aflibercept for the treatment of DME.

 Originally, aflibercept was approved as a first-line therapy for patients with severe DME, when visual loss has increased because of edema involving the center of the macula.

In countries with abundant resources, patients benefit from intravitreal injection anti-VEGF therapy to treat DME. However, in underserved countries with less resources where the prevalence of DME may be higher, this option may not be available, and less expensive alternatives such as biosimilars must be considered.

To determine the therapeutic similarity of CT-P42 compared with aflibercept, patients with DME were enrolled in a randomized, active-controlled, double-masked, phase 3 clinical trial. They either received the aflibercept biosimilar candidate, CT-P42, or reference aflibercept by intravitreal injection every 4 weeks followed by every 8 weeks in the main study period.

Data collection began when the first patient was randomized on July 22, 2021, and ended at week 24 for the last patient on October 14, 2022. A total of 348 patients were randomized throughout the study, with 173 patients who took CT-P42 and 175 patients who took reference aflibercept.

The study population was mainly White (64.4%) and male (58.3%), with a median age of 63 years. Most patients had type 2 diabetes (93.1%) rather than type 1 diabetes (6.9%). More than half of the patient population (72.7%) had a baseline best corrected visual acuity (BCVA) score of at least 55 letters. The average BCVA scores were 60.3 and 60.4 in the CT-P42 and reference aflibercept groups, respectively. 

By the end of week 24, most patients completed the study from start to finish (96.3%). There were more patients who took CT-P42 that completed the study (97.1%) than the patients who took reference aflibercept (95.4%).

Very few patients discontinued the study on or before week 24 in the CT-P42 group (2.9%) or the reference aflibercept group (4.6%). Discontinuation was mainly due to withdrawal by the patient (CT-P42, 1.2%; reference aflibercept, 1.7%).

Efficacy, Pharmacokinetics, and Safety of CT-P42 in DME

Both the CT-P42 (9.43 letters) and reference aflibercept (8.85 letters) groups demonstrated improved visual acuity from baseline to week 8. The treatment difference between groups was minimal (0.58 letters) and within the prespecified equivalence margin (95% CI, −0.73 to 1.88). Similar efficacy was observed for both groups in other key retinal outcomes through week 24, confirming therapeutic equivalence.

Similar PK parameters were found among both treatment groups, with low plasma concentrations and no evidence of drug accumulation. At week 0, all injections with the vial kit were successfully administered without any user errors or close calls in either treatment group.

Treatment-emergent adverse events (TEAEs) were similar across treatment groups, at 50.3% and 53.7% of patients in the CT-P42 and reference aflibercept groups, respectively. The majority of the TEAEs were grade 1 to 2 in intensity, the most frequent being conjunctival hemorrhage (CT-P42, 1.2%; reference aflibercept, 2.3%) and intraocular pressure increased (CT-P42, 1.2%; reference aflibercept, 1.7%).

Both groups were comparable in the incidence of nonocular TEAEs reported, with 38.7% of patients in the CT-P42 group and 38.3% in the reference aflibercept group. The study population primarily comprised patients with negative antidrug antibody results for the initial 24 weeks. Immunogenicity profiles remained similar across groups during this period.

Study limitations included a small, predominantly White patient population and short-term follow-up. Long-term safety and efficacy data for CT-P42 in real-world settings are necessary.

“This study demonstrated equivalence of CT-P42 and reference aflibercept at a dose of 2 mg in 0.05 mL in terms of efficacy. The PK, usability, safety, and immunogenicity profiles of CT-P42 and reference aflibercept were also comparable in patients with DME,” the authors concluded.

1. Wolf S, Stanga PE, Veselovsky M, et al. Biosimilar candidate CT-P42 in diabetic macular edema: 24-week results from a randomized, active-controlled, phase III study. 

. 2024;1-22. doi:10.1016/j.oret.2024.06.013

2. Gupta N, Mansoor S, Sharma A, et al. Diabetic retinopathy and VEGF. 

. 2013;7:4-10. doi:10.2174/1874364101307010004

3. What is diabetes-related edema (DME)? Cleveland Clinic. February 14, 2023. Accessed August 12, 2024. 

https://my.clevelandclinic.org/health/diseases/24733-diabetes-related-macular-edema

Biosimilar CT-P42 demonstrated comparable efficacy, safety, and tolerability to reference aflibercept in treating diabetic macular edema (DME).

Biosimilar CT-P42 Demonstrates Equivalence to Aflibercept for DME

In an interview with The Center for Biosimilars

, Ha Kung Wong, JD, an intellectual property attorney and partner at Venable LLC, provided an overview of the patent legal system biosimilars must navigate under the Biologics Price Competition and Innovation Act (BPCIA) of 2009. He explained that the BPCIA establishes an optional framework for information exchange between biosimilar developers and reference product sponsors, commonly known as the "patent dance."

This process helps narrow down patent disputes before litigation, potentially reducing the number of patents involved and promoting early settlements. Wong highlighted the benefits of this system, noting that it can streamline the approval process for biosimilars, save resources, and lead to favorable outcomes for both parties. Additionally, he discussed ongoing legislative efforts that could impact the biosimilar sector, including potential reforms to patent laws and scrutiny of pharmacy benefit managers (PBMs).

Can you explain the patent legal system biosimilars are required to undergo and why this process is important to their development?

 Sure, so for biosimilars, there's the BPCIA or the Biologics Price Competition and Innovation Act of 2009, which is actually an optional framework of information exchanges between biosimilars and the reference product sponsor, or what we call the RPS, prior to filing an infringement lawsuit.

The BPCIA allows for 2 phases of litigation. One, following the biosimilars aBLA [abbreviated biologics license application] submission and the second phase triggered by the biosimilars notice of commercial marketing. Now, the idea is that the most important patents can be dealt with while the biosimilar application is under FDA review. That gives the possibility of resolving the lawsuit after only litigating a small subset of patents, instead of the RPS' entire portfolio. That can be quite large and sometimes in the hundreds.

So, to start this first phase exchange of materials, which is often referred to as the patent dance, the biosimilar notifies the RPS that the FDA has accepted its biosimilar application within 20 days of that acceptance and provides the RPS with its aBLA and "other manufacturing information".

That starts off this kind of exchange of information regarding the patents that might be infringed by the biosimilar and which they think might be likely to be licensed whether the biosimilar feels like there is an infringement, validity, or enforceability problem or not. Ultimately, what happens in the first round of litigation is that you narrow the number of patents that you actually litigate right away. If the parties can't agree, the BPCIA gives a provision for determining the list of patents that can be litigated in the first phase and the remainder gets litigated in the second phase.

For most BPCIA litigations that most parties have participated in at least some part of the dance and as I mentioned before, it was after the statute came out it was decided by the courts that this was optional.

A lot of people said, "Well, why would anybody go through this?" It turns out, it helps both sides, right? The biosimilar gets that chance to narrow it down to the patents that are most important so they're not expending an enormous amount of resources litigating hundreds of patents, and the RPS gets a chance to really zone in on the patents that are most important to them and try to protect them first, then try to seek licenses on those that can be some sort of settlement. So 24 of the litigations that have occurred, have completed this entire patent dance, 19 participated in some portion of it and didn't finish, but only 9 didn't participate.

You can see that even though it's optional, a lot of parties find some benefit to going through this process. Now, the interesting thing about it is that when it came out, I thought this is the most half-baked process ever.

That's still true, but it's better than nothing is what I think is happening. Most of the BPCIA litigations are actually ending in settlements. Thirty-one of 46, or 67%, of terminated BPCIA litigations ended in settlement or stipulated voluntary dismissals.

Very few cases have gotten the verdict, which is actually part of what we want. I think this statistic that I'm raising is demonstrating that the primary benefit of the BPCIA process is being met. That was to resolve any patent related disputes early, prior to impact on the market, thus allowing both parties to direct resources appropriately to their respective products and avoid the need to address potential damages.

In many ways, this is similar to what the Hatch-Waxman process was meant to address for small molecules. So far, it appears to be working for biologics and biosimilars, and really helping in development on both sides.

Do you foresee any potential shifts or reforms in patent law that could positively or negatively impact the biosimilars sector in the near future?

 Predicting whether there will be statutory shifts or reform in patent law is like trying to predict what will happen in the next Fast & Furious movie—you have no idea what specifically is going to happen but it's probably going to have some explosions that ultimately, will not be applicable to the real world. That being said, there are a few things I think that we might want to keep an eye on. I say "very few" only because we've seen a lot of things introduced and not a lot of follow through. There's a lot of good intentions out there, but there's not a lot of follow through. That being said, here it is.

First of all, Senators [Peter] Welch [D, Vermont], [Mike] Braun [R, Indiana], and [Amy] Klobuchar [D, Minnesota] introduced legislation in the Senate, and Representative [Jodey] Arrington [R, Texas] in the House in January 2024 that would limit the number of patents that could be asserted in a patent litigation. If this were to proceed, this may or may not have a practical effect because we've seen that most Bundled Payments for Care Improvement (BPCI) lawsuits that have been asserted are asserted on 10 or less patents. So, having an artificial limit may not make it any better. But it might. Who knows? It is certainly something to keep an eye on.

The Biosimilar Red Tape Elimination Act was introduced in July 2023 by Senators [Mike] Lee [R, Utah], [Ben Ray] Lujân [D, New Mexico], Braun, and [J.D.] Vance [R, Ohio]. That bill would eliminate the 2 separate designations of biosimilars and interchangables, which we know, exist in the US and we are the only country that does that. Every other country in the world only has 1 level of biosimilarity. It's possible if the interchangability requirement was removed, there could be greater uptake of biosimilars due to the possibility of automatic substitution at the pharmacy level, like we see with generic drugs. There may be increased confidence in biosimilars because they would be seen as perhaps closer to the reference product.

The problem is that when people hear there's a "biosimilar" but there's a higher level called "interchangable", their automatic reaction is, "Well that means biosimilars are garbage, why would I want that? I want an interchangeable. Oh, there's no interchangable? Then I don't want that product."

I think it will help with consumer confidence, patient confidence, and will help with health care provider confidence because a lot of doctors just don't know the difference.

In June 2023, Senators [Thom] Tillis [R, North Carolina] and [Chris] Coons [D, Delaware] reintroduced the Patent Eligibility and Restoration Act of 2023 to reform patentability requirements under Section 101. There, the bill seeks to clarify which inventions are eligible for patenting in the US. If that bill were to be passed, it would overturn Supreme Court decisions in Mayo, Alice, and Myriad, which we've all been talking about for 10 years. It would be really interesting to see how that would impact the pharmaceutical and biologics industry in particular.

Finally, there's been this increased congressional scrutiny of pharmacy benefit managers or PBMs. Congress has launched various investigations into PBM practices and while this isn't directly related to patent law reform, it could have a significant impact on biosimilar uptake given the preferential formulary coverage of biosimilars and how that plays a big role in whether biosimilars are used and whether cost savings are realized or not.

I've been on record saying this for a long time now. PBMs are middlemen that don't need to really be there, but at the end of the day, they end up increasing the cost for patients and it would be interesting to see if all this congressional scrutiny will lead to better cost savings for patients.

Recently, CareFirst BlueCross BlueShield filed a lawsuit against J&J alleging that the company is “scheming” to delay ustekinumab biosimilar competition. How do you expect this case to play out and what impact could it have on the overall biosimilar industry?

 This is not the first antitrust suit to be filed related to a biosimilar and biosimilar competition, particularly on drugs that are costly so it really isn't surprising to see another antitrust suit.

As a side note, talking about antitrust always reminds me of the 2001 movie Antitrust starring Ryan Phillippe and Rachael Leigh Cook, but I digress.

Previous antitrust suits, you know that I think we want to think about in conjunction with this one would be the 

Remicade exclusionary contracting class action lawsuit

. That actually was settled by consumers, third party payers for $25 million.

Remicade exclusionary contracting lawsuit by Inflectra

 biosimilar manufacturer, Pfizer. There was an undisclosed settlement agreement there.

, which found that filing numerous patent applications was a form of petitioning the government, qualified for Noerr-Pennington immunity and that protects the filing under the First Amendment petition and free speech clause.

Even if the petition is anticompetitive, it's immune from antitrust action. I bring those up because so far, the biosimilar antitrust suits may have had some positive impact on decreasing the usage of exclusionary contracts to prevent biosimilar formulary coverage.

However, it's yet to be seen maybe debatable how steep of a deterrent something like a $25 million settlement is on a drug similar to Remicade, which is making over $6 billion a year.

It’s unclear whether another antitrust lawsuit will have a significant impact on biosimilars going forward or not. But certainly, something that we should keep an eye on and certainly something we should be vigilant about.

What are the key objectives of the patent dance, and how does it contribute to streamlining the exchange of information while reducing the potential for wasteful litigation?

 The patent dance allows for an early assessment of infringement and validity patient positions, even before the filing of a litigation and that can help parties reach an early settlement.

Part of the process here is don't slow down biosimilar approval process, don't subject them to damages from launching at risk. Let's resolve all the patent issues in advance or at the time in which you're looking to get approval, such so that you can get it resolved at the time you get approval.

If you don’t have a problem with the patents, then you can launch without any risk and you're okay. If you do, let's sort that out.

 does for small molecules and that's what this 

 patent dance does for biosimilars and it's been really effective.

I think it’s led to a great number of settlements, very few of them go to trial, which means we're not wasting resources on litigation. As much as I do litigation, so I like to have litigation, I think for my clients, it's a win-win all the way around.

Also, the case management mechanisms have been very effective at limiting the size of the litigations. For example, in the recently decided 

 relating to Eylea, despite 24 patents initially being asserted, the case was initially narrowed to set 6 patents, and then further narrowed to 3 patents for an expedited trial that provided the companies with resolution.

One patent was found valid and infringed without having to litigate all the asserted patents. I think, by and large, it’s working to really save resources for all parties involved. If it has to go to litigation, it goes but it also is resulting in favorable settlements in which everybody wins.

How are “patent thickets” formed, why are companies allowed to create them, and what needs to be done to ensure that the supplemental patent system does not block biosimilar competition and disincentivize innovation?

 I think that what we're talking about here when we say "patent thickets" are larger patent portfolios that have significantly overlapping patent rights that make it more challenging for competitors to design around than for instance, a single patent. Now, for biologics, these may be created by obtaining a number of different types of patents that cover a product.

For example, there may be patents that cover the antibody, then the formulations of the antibody, methods of using the drug, ways that drugs are manufactured, devices for administration of the drug, a lot of times biologics require injections so that's oftentimes important or even ways of packaging the drug.

Now, because 1 or more patents can be obtained within each of these patent types, different aspects of a drug and its manufacturer can end up being covered by a number of different patents. Therefore, you have this grouping of patents but keep in mind that often in development of biologics products, it's unclear early on what the commercial product will be.

Since patents are first to file in the United States, biologics innovators typically file composition of matter patents early, because they have to reserve their rights. That's usually way before they have an idea of what the specific active moiety will be that goes into clinic and certainly before knowing what the active moiety will be in the product that's made available to patients.

Additional patents are typically filed later in the development process, when the moiety becomes clear and when the formulation and method of treatment are developed, which could be way after the initial drug discovery is completed.

Interestingly, a recent study, I believe it was the 

, noted that the effective patent life for a patent and a product is about 12 years.

The effective patent life is essentially the time from drug approval to expiration, not the time that you file it. So, you notice that that's not the 20 years you normally get from a patent, it's much less. If a biologic innovator wants patent protection that exceeds the BLA regulatory exclusivity from the FDA, which is itself 12 years, they typically file later patents that cover other aspects of their product beyond simple composition of matter.

There's certainly some balance that has to be struck here, as we also don't want to unduly inhibit the ability of biosimilars to reach the market and potentially increase accessibility to patients. I think we have to be kind of vigilant about that kind of give and take. There are already some systems in place to prevent unfairly blocking competition, such as the use of terminal disclaimers and skinny labeling, which allows biosimilars to enter the market for some unpatented indications while removing the patented indications from their labels.

In addition, the FDA and USPTO [United States Patent and Trademark Office], have collaborated a lot and discuss about how to make sure only good patents are allowed. I think that also the use of PGRs [post-grant reviews] and IPRs [inter partes reviews] by biosimilar manufacturers have kept a lot of innovators honest in terms of the patents that they seek to procure. So, there's a number of things that are in place but we have to be vigilant about it.

In an interview, Ha Kung Wong, an intellectual property attorney, explained that the Biologics Price Competition and Innovation Act of 2009 provides a structured but optional "patent dance" for biosimilars, which helps streamline patent disputes, potentially reducing litigation and encouraging early settlements.

Patent Dance Insights: A Q&A on Reducing Legal Battles in the Biosimilar Landscape

The Top 5 Biosimilar Articles for the Week of August 12

Artificial intelligence (AI) technologies

 can support global health systems in integrating biosimilars into care models, reducing health care costs, enhancing treatment decision-making strategies, and narrowing the gap between high-income and low- and middle-income countries.

 receive good news regarding their ustekinumab biosimilars; Lupin Limited completes a phase 3 trial for a ranibizumab candidate; Julie Reed, MS, executive director of the Biosimilars Forum weighs in on pharmacy benefit managers and biosimilar access.

, also known as the "Affordable Prescriptions for Patients Act of 2023," aims to reduce drug prices by addressing anti-competitive practices such as patent thickets and product hopping, which hinder the entry of cheaper biosimilars and generics into the market.

 means that all 10 Canadian provinces now have an initiative to boost biosimilar adoption and savings by transitioning patients on reference agents to biosimilar options.

Here are the top 5 biosimilar articles for the week of August 12, 2024.

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 examined the integration of clinical practice and health economics research to expedite biosimilar access, in an interview with The Center for Biosimilars®.

Abraham highlights the established safety and efficacy of reference drugs, arguing that rigorous cost-effectiveness studies for biosimilars may not be necessary.

This transcript has been lightly edited for clarity.

How can the integration of both clinical practices and health economics research fall into the biosimilar development process to expedite access for patients while maintaining rigorous scientific evaluation?


The critical part here is really the fundamentals now of biosimilars come in and that's the economics. People say "yes, but don't we need cost effectiveness studies on biosimilars?" Well, if we know that another drug, your reference drug, has a certain level of cost effectiveness, clinical and safety outcomes relative to cost, we don't need to replicate an analysis like that because we know that statistically, our biosimilar product has equivalent margins in safety and effectiveness.

What we need to focus on here is if we have a biosimilar, relative to a reference product, and there is a price differential, it's no rocket science, you're going to have savings efficiencies.

That's where most payers really stop, although some of them have begun to listen to alternatives but what do we do with those savings? We can provide access on a budget neutral basis to either more biosimilar or to totally new treatments that at this moment, some patients, perhaps many patients, would not be eligible to receive but where a payer could say, "okay, we achieve efficiencies here and let's now put that to some good use and make more of our members have the care that they should have, but that at this moment, our guidelines do not cover."

That brings us to really a global aspect of biosimilars and that is that biosimilars have the potential because of cost differentials to promote access and equity in health care to people who otherwise might not get it. Now, within the clinical environments, we need to remember, the decisions are not necessarily made at the point of care.

Ivo Abraham, PhD, RN, University of Arizona Cancer Center, focused on the cost savings generated by biosimilars and how crucial reinvesting those savings into broader patient access to care is. This approach has the potential to improve health care equity and expand treatment options for patients.

Bridging Clinical Practice, Health Economics for Improved Patient Access

The Top 5 Biosimilar Articles for the Week of August 5

 a lot of discussion regarding biosimilar policies, in both the US and abroad, as well as 3 highly anticipated FDA approvals.

 predicted in 2025, several originator biologics set to face biosimilar competition in the next few years are projected to increase their list prices, according to 

Vizient’s Pharmacy Market Outlook Report for Summer 2024

 Value-driven health care strategies in Singapore’s public institutions have significantly increased biosimilar adoption, leading to reduced treatment costs and substantial savings for the health care system, 

 now available has helped countless patients deal with diseases for which traditional treatments were unsatisfactory. Individuals who have autoimmune diseases, cancer, and diabetes have benefited, as have those with previously untreatable genetic diseases. The most complex biologics first entered the market in the 1980s and 1990s, and for this reason, many of their patents are expiring. The concept of biosimilars was a rational idea that loosely mimicked the idea of generic drugs. However, because biologics are large, 3-dimensional, complex molecules, it took some time for regulatory agencies around the world to develop appropriate regulations.

 on glycan profiling of monoclonal antibodies (Mabs) receives praise and recommendations from Sarfaraz K. Niazi, PhD.

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

In a comprehensive analysis,the biosimilar SB15 exhibited high similarity to reference aflibercept in terms of physicochemical and biological properties. | Image Credit: 

The physicochemical and biological properties of SB15, a biosimilar product referencing aflibercept (Eylea), was highly similar to aflibercept reference products in the US and European Union (EU) in a study from

The findings support safe and effective use of SB15, according to the authors. 

Both the FDA and European Medicines Agency (EMA) approved aflibercept, aVEGF inhibitor, for a a range of ocular diseases such as neovascular age-related macular degeneration (nAMD), macular edema following retinal vein occlusion, diabetic macular edema, and diabetic retinopathy.

The FDA approved aflibercept in November 2011, along with Japan, Australia, Switzerland, and other countries.

 However, the EMA did not approve aflibercept until the following year, in November 2012.

More recently, Samsung Bioepis developed SB15, a biosimilar to reference aflibercept.

Earlier this year, a multi-region study proved comparable safety, efficacy, immunogenicity, and pharmacokinetics in SB15 vs reference aflibercept for first-line treatment after patients switched from aflibercept to SB15 in nAMD.

Aflibercept is an anti-VEGF agent that harbors the binding domains of vascular endothelial growth factor (VEGF) receptors 1 and 2 while blocking all VEGF-A isoforms, VEGF-B, and placental growth factor.

 The biosimilar, SB15, is produced by a recombinant DNA technology and was developed to reference aflibercept.

An analytical panel was used to comprehensively characterize SB15 compared with the US/EU-sourced aflibercept.

 Every sample included in the study was handled in a sterile manner in a biological safety cabinet. 

The analysis examined primary structure, higher-order structure, physicochemical properties, and functional activities. The molecular weights of SB15 and US/EU aflibercept were comparable for the deglycosylated and reduced samples.

The intact molecular weights of SB15 and US/EU aflibercept were also comparable based on single-chain molecular weight, disulfide linkage, and site-specific N-glycosylation analysis. The primary structure did not have any meaningful differences observed in biological activities.

Higher-order structural comparisons using circular dichroism and differential scanning calorimetry revealed high similarity between SB15 and the reference aflibercept products. Circular dichroism analyzes protein structure through polarized light,

while differential scanning calorimetry assesses protein stability by measuring changes in heat flow.

In terms of size and charge heterogeneity, there were no meaningful differences in the physicochemical properties between SB15 and its reference product.

In a comprehensive analysis, the biosimilar SB15 exhibited high similarity to reference aflibercept in terms of physicochemical and biological properties.