Cameron Santoro is an associate editor for The Center for Biosimilars

Cameron Santoro

Adam Colborn, JD. 

Adam Colborn, JD, director of government relations for the Academy of Managed Care Pharmacy, explores the efforts policymakers can take towards interchangeability and ultimately remove switching study requirements altogether. Colborn delves into the different regulations the US and Europe have when it comes to biosimilars. He stresses the importance in equipping pharmacists with proper educational resources and training that ensures confidence among biosimilar interchangeability.

Colborn presented his session titled, "Breaking Boundaries with Interchangeable Biosimilars: The Sequel", at 

the Academy of Managed Care Pharmacy (AMCP) 2024

 annual meeting, where he discussed the regulatory landscape of interchangeable biosimilars, their outcome on formulary management and benefit design, as well as emerging regulatory trends. Operating as the director of government relations, Colborn has led advocacy and state policy work through his support of AMCP's direct federal Congressional lobbying. His professional experience in public policy and professional advocacy has allowed Colborn to work on both state and federal levels.

What should policymakers keep in mind as they work to clarify interchangeability or make efforts to remove switching study requirements or the designation altogether?

I think the most important thing for regulators and policymakers to keep in mind as they're looking at potentially eliminating switching studies from the requirement to designate a biosimilar as interchangeable is how that's worked out in Europe.

There's some data that's come out recently from Europe that switching studies do not offer any additional information beyond the typical interchangeable, interchangeability application process. So that extra step really seems to be an unnecessary hurdle to the process. I think I would look at what other countries, mainly Europe, have done in that space before.

Pharmacists play a crucial role in dispensing interchangeable biosimilars. How can we ensure they are equipped with the necessary knowledge and training to confidently counsel patients on biosimilar interchangeability?

I think pharmacists, like other types of providers, need additional education on the biosimilar issue. Right now, the legal framework for biosimilar interchangeability is very complicated. For example, a biosimilar that is interchangeable with the reference product is not automatically interchangeable with another biosimilar. That's been a big obstacle for uptake of biosimilars because when we look at generic switching, it's much easier for someone to say well, I have X generic in stock so I'll dispense that instead of Y generic.

With biosimilars, they don't have that flexibility. In addition to the education to make pharmacists more comfortable with biosimilar interchangeability and switching, I think policymakers need to step in and take a role in clarifying when a biosimilar can be switched for another biosimilar that has been designated as interchangeable with the reference product.

Videos

In an interview with Adam Colborn, JD, director of government relations for the Academy of Managed Care Pharmacy focuses on biosimilar interchangeability and approaches to encourage wider adoption in dispensing these medications. 

Adam Colborn Reviews Biosimilar Interchangeability Requirements, Advocates for Pharmacist Resources

The Top 5 Biosimilar Articles for the Week of April 22

 Sarfaraz K. Niazi, PhD, outlines the current state of 

 in the US and policy changes needed to clear up misconceptions surrounding the meaning behind interchangeability designations.

 (tocilizumab-aazg) was the second tocilizumab biosimilar to be FDA approved, but it is the first to launch in the US.

 Alvotech’s Selarsdi (ustekinumab-aekn), a 

 (ustekinumab), gained FDA approval, making it the second ustekinumab biosimilar and second for the company to be given the green light for the American market.

, executive director of the Biosimilars Forum, showcases how the biosimilar industry is expected to develop throughout 2024, including major policy changes and hope for continued improvement in market share for adalimumab biosimilars.

 in the American Oncology Network (AON) have saved the organization over $243 million between 2020 and 2023, according to Melody Chang, vice president of pharmacy operations at AON.

To read all of these articles and more, visit 

Here are the top 5 biosimilar articles for the week of April 22, 2024. 

Market uptake | Image Credit: xyz+ - stock.adobe.com

Collective action theory was a proposed solution for stakeholder disagreements stalling biosimilar uptake because it fosters collaboration and achieves widespread biosimilar use for long-term benefits.

 focused on various approaches applied as long-term solutions for biosimilar markets. Several trends raise concerns about the biosimilar market, such as a limited pipeline of new drugs in development, a focus on developing biosimilars only for high profit areas, and an increasing number of biosimilars being discontinued or withdrawn.

Disagreements surrounding stakeholder strategies attempted to regulate the supply and demand chain of biosimilars. Usually, stakeholder disagreements revolve around competing interests that come into conflict in the short term and undermine joint long-term goals.

On the supply side, payers and health care site managers are looking to reduce costs by decreasing drug prices through biosimilar savings, a short-term objective. Concerns were addressed by stakeholders surrounding mainly potentially anticompetitive procurement practices that reinforce the originators’ market dominance while tendering procedures that lead to selections of a biosimilar product as a single winner.

With negative effects on the competition environment for biosimilars in mind, care providers have raised awareness on the impact limited competition has on continuity in the supply of biologics and ultimately, patient care. Supply issues, largely affecting the market of generic medicines could soon extend to biosimilar markets, increasing the number of biosimilar withdrawals and discontinuations.

The demand side includes policy and decision-makers that advocate for biosimilar policies to increase early uptake and generate substantial savings. Application of mandated nationwide switch protocols were one solution to drive uptake. It should be noted that even if solutions neglect sustainability concepts, it is still capable of producing short-term benefits.

Proposed solutions, particularly mandatory switching protocols, often face resistance from health care professionals and patients. Unlike payers and policymakers focused on cost savings, health care professionals prioritize patient care and may disagree with rapid switches that lack sufficient time or resources. Similarly, patients are hesitant to switch therapies unless they see clear benefits in terms of accessibility and affordability.

Successful community driven initiatives have been successful based on their ability to promote multi-stakeholder consensus efforts. Although, challenges included the scale of these initiatives while ensuring durability is in the absence of a detailed oriented understanding of the required principles, and socioeconomic and policy environments.

Communication between stakeholders surrounding biosimilar savings and the reallocation of savings generated some differing perspectives. Some stakeholders suggested the need for greater transparency and local reallocation strategies while others examined the totality of generated savings that should meet the demand of the central health administration.

Based on collective action theory, “social dilemmas” can be prevailed if stakeholders were more open to “cooperate” design and implementation strategies for long term societal benefits. This potential solution is relevant in investigating collective action theory as a conceptual framework to advise prospective policy reforms for biosimilars.

Newfound knowledge from the collective action theory was applied to support sustainable biosimilar markets. Collective efforts and joint responsibility of stakeholders in health care are requirements for creating a sustainable biosimilar market.

Effective policy frameworks rely on multistakeholder input, long-term visions, aligned incentives, cost benefit analysis, intergovernmental coordination, clear goals, and efficient complaint as well as outcome monitoring. Research shows past policies lacking these elements faced implementation hurdles.

More research is necessary to accurately measure how much stakeholders agree with the described sustainability principles and to develop a dependable framework that can be applied to specific situations in the biosimilar market. It's important to consider political and economic limitations, as they can make it difficult to apply theory into practice when evaluating individual cases.

Lacosta TB, Vulto AG, Turk F, Huys I, Simoens S. Can endangered biosimilar markets be rescued? The need to bridge competing interests for long-term gain. 

. 2024;1-5. doi:10.1007/s40259-024-00652-7

Articles

Despite current challenges in biosimilar market growth due to stakeholder disagreements, a recent commentary proposes that applying collective action theory can achieve widespread biosimilar market uptake by fostering collaboration for long-term benefits.

Sustainable Biosimilar Markets Achieve Widespread Market Uptake Through Collective Action

Ha Kung Wong, JD. 

In this interview for The Center for Biosimilars

, specializing in patent law, discusses patent thickets and their impact on biosimilar development. Patent thickets are formed when a company obtains a large number of overlapping patents related to a single product, making it difficult for competitors to develop similar products without infringing on those patents.

Wong acknowledges the importance of patents for rewarding innovation in biologics, but also emphasizes the need for balance. Patent thickets can create barriers to biosimilar entry, which could limit patient access to these more affordable medications. Fortunately, there are mechanisms in place to mitigate this, such as terminal disclaimers and post-grant reviews, which help ensure only high-quality patents are granted and prevent unfair competition.

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 it's 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 [biologics license applications] 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.

Ha Kung Wong, JD, a patent attorney, explores the challenges of "patent thickets" in the biologics market, where a complex web of patents can hinder development of more affordable biosimilar drugs. However, the discussion also highlights mechanisms to ensure fair competition and patient access.

Navigating the Patent Thicket: Balancing Innovation, Biosimilar Access in the Biologics Market

The Top 5 Biosimilar Articles for the Week of April 15

 Data from 2021 and 2022 showed that biosimilar use within an 

 was on the rise, suggesting that the country could achieve total utilization in the coming years. The researchers touted the growing success, saying that more use will benefit the National Health System (NHS) and citizens who rely on an efficient and sustainable health care policy.

 evaluating IQVIA data found that rebate schemes orchestrated by pharmacy benefit managers (PBMs) are costing US patients and payers billions of dollars by suppressing biosimilar adoption.

 is projected to surge from $25.1 billion in 2022 to approximately $1.3 trillion by 2032, with a compound annual growth rate of 17.6%, driven mainly by the increasing prevalence of cancer and the cost-effectiveness of biosimilars, as outlined in a report by Towards Healthcare.

 After poor sales for its adalimumab biosimilar, Boehringer Ingelheim (BI) announces layoffs; Teva Pharmaceuticals and mAbxience 

; Samsung Bioepis begins a phase 3 trial for a biosimilar referencing Keytruda (pembrolizumab).

Here are the top 5 biosimilar articles for the week of April 15, 2024.

Illustration of biosimilar medicines | Image Credit: TarikVision - stock.adobe.com

The combination of sintilimab, a low dose of bevacizumab biosimilar (IBI305), and hepatic arterial infusion chemotherapy (HAIC) showed promising efficacy and safety in treating patients with unresectable hepatocellular carcinoma (HCC).

Researchers at the Tianjin Medical University Cancer Institute and Hospital in China conducted a 

The trial involved patients with HCC who hadn't undergone any prior systemic therapy for their cancer. From May 2021 to October 2021, the enrolled patients received a combination treatment of sintilimab (200 mg), IBI305 (7.5 mg/kg), and HAIC (folinic acid, fluorouracil, oxaliplatin for 23 hours) every 3 weeks.

Primary endpoints were the objective response rate (ORR), mainly based on the pathologic results of patients after surgical treatment with the drug, and the treatment-related adverse events (TRAEs). Secondary endpoints included the event free survival (EFS), overall survival (OS), the pathological complete response (pCR) rate, and the surgical conversion rate. Researchers observed disease control in patients with partial responses (PR) and stable disease (SD).

The patients that reached conversion surgery criteria were administered another cycle of sintilimab and HAIC. Contrast-enhanced computed tomography or magnetic resonance imaging were used to assess tumors at baseline and after the third to the sixth cycle of treatment to evaluate resection probability.

A total of 30 patients were enrolled in the study with their safety outcomes analyzed. After 1 voluntarily withdraw, 29 patients completed antitumor efficacy outcomes, conversion therapy, and the tumor assessments.

Participants had a median age of 55.5 years, included 26 males (72.2%), over a 3-cycle treatment duration period. The study population consisted of 79.3% of patients with hepatitis B and 13.8% with hepatitis C. The most common observations made among patients were vascular invasion (51.7%) or extrahepatic metastasis (48.3%).

Results met the primary endpoint with 17 (58.6%) of 29 unresectable HCC patients that were assessed by an independent review committee achieved ORR. About 23 of 29 patients observed disease control with partial response (PR) in 17 (58.6%) patients and stable disease in 6 (20.7%). Following conversion treatment, a-fetoprotein levels decreased (

Among 20 patients, further treatment was successfully converted (69%). Although, 1 patient refused further treatment and 19 patients were included in the final count. Tumor remission status of 14 patients underwent resection, 3 underwent radiofrequency ablation, 2 underwent biopsies to compare treatment effects, and all patients achieved R0 resection. Only 1 patient (5.3%) achieved pCR and 5 patients (26.3%) reached major partial response after undergoing pathological examinations using surgical specimens or biopsy specimens.

On average, follow-up ranged over 19.3 months. The OS rate of the 29 patients after 3, 6, 9, and 12 months was 93.1%, 86.2%, 72.4%, and 65.5%, respectively. The EFS rates for 3, 6, 9, and 12 months were 89.7%, 62.1%, 44.8%, and 41.4%.

Clinical remission was achieved by 1 group of patients while another group achieved SD or PR. After 1 year, OS rates of the PR group (n =17) and PD plus SD group (n =12) were 82.4% and 41.7%. After 1 year, EFS rates of the PR group and PD plus SD group were 52.9% and 25%.

The most common TRAEs included thrombocytopenia (40%), hypertension (23.3%), leukopenia (23.3%), hypertension (10%), diarrhea (6.7%), asthenia (3.3%), and ascites (3.3%). There were no serious adverse events (AEs) detected.

Study limitations include doses of treatment because fewer AEs could have occurred with lower medication doses. As a result of AEs, patients had poor compliance with treatment.

Results suggest that sintilimab combined with bevacizumab biosimilar and HAIC could be an effective and well-tolerated treatment for patients with unresectable HCC. However, larger studies are required to solidify these findings and determine its wider use in the future.

Liu D, Mu H, Liu C, et al. Sintilimab, bevacizumab biosimilar, and HAIC for unresectable hepatocellular carcinoma conversion therapy: a prospective, single-arm phase II trial. 

. 2024;70(06):811-818. doi:10.4149/neo_2023_230806n413

Positive results of sintilimab, IBI305, and hepatic arterial infusion chemotherapy (HAIC) treatment showed shrinking tumors and previously converting inoperable hepatocellular carcinoma (HCC) to resectable HCC with manageable adverse effects.  

Sintilimab, Bevacizumab Biosimilar, HAIC Improves Survival in Patients With Unresectable HCC

The Top 5 Videos for the Week of April 8

 A systematic review and meta-analysis of 7 randomized controlled trials found 

 in efficacy and safety indicators between adalimumab biosimilars and the reference product (Humira) for treatment of moderate to severe psoriasis.

 A Chinese company has expressed interest in developing a 

 (semaglutide), a popular drug used for diabetes and weight loss; Biocon and Mylan are in talks to merge their biosimilar businesses; Celltrion completed its biologic license application (BLA) for its omalizumab biosimilar candidate.

 Although tender systems are a common strategy to encourage biosimilar utilization across Europe, policies like automatic substitution are rarely utilized, according to a systematic review of 

Sarfaraz K. Niazi, PhD, outlines how President Joe Biden's 

 could impact biosimilars, including provisions to clear up confusion surrounding interchangeable products.

Here are the top 5 biosimilar articles for the week of April 8, 2024. 

The Top 5 Biosimilar Articles for the Week of April 8

Ha Kung Wong, JD.

In an interview with The Center for Biosimilars

, Ha Kung Wong, JD, an intellectual property attorney and partner at 

, dives into the advantages of the patent dance. Wong, a specialist in intellectual property law, explores how this process streamlines information exchange and minimizes unnecessary lawsuits.

The patent dance, Wong explains, establishes a framework for early disclosure of patents and potential infringement concerns between biosimilar developers and reference product sponsors. By enabling early assessment of patent validity and infringement, it empowers parties to reach settlements before product launch, saving both time and money.

This approach mirrors the Hatch-Waxman Act for traditional drugs and has demonstrably reduced litigation in the biosimilar space. Even when lawsuits become necessary, the patent dance helps focus on the most critical patents, minimizing resource expenditure for all involved.

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 

 [Biologics Price Competition and Innovation Act] 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.

Intellectual property attorney Ha Kung Wong, JD, describes the patent dance and how it is designed to streamline information exchange while avoiding unnecessary lawsuits by allowing early assessment of patent infringement and validity.

Streamlined Approach to Biosimilar Approval Reduces Litigation Risk

The Top 5 Biosimilar Articles for the Week of April 1

 described the totality of evidence supporting the approval of the adalimumab biosimilar AVT02 (Simlandi; Alvotech) for all approved indications of the reference product, Humira.

 Sarfaraz K. Niazi, PhD, outlines how President Joe Biden's 

The Association for Accessible Medicines’ 

 on Medicare Part D tiering revealed low coverage rates for insulin and adalimumab biosimilars across plans.

 reintroduce the Increasing Access to Biosimilars Act, a bipartisan bill aimed at boosting competition and encouraging providers to prescribe biosimilars, to Congress.

Despite more biosimilars entering the market and generating significant savings for payers and health care systems, these savings are not resulting in lower 

 for patients, according to a recent study.

Here are the top 5 biosimilar articles for the week of April 1, 2024.

The Top 5 Biosimilar Articles for the Week of March 25

 A real-world study surveying physicians and patients on adalimumab biosimilar ABP 501 (Amgevita) in inflammatory bowel disease (IBD) found both patients initiating 

 and those who had switched from the reference product had higher satisfaction levels.

Sarfaraz K. Niazi, PhD, explains how the new 

 under the Medicines and Healthcare Products Regulatory Agency (MHRA) could expand biosimilar access within the United Kingdom, in his latest column.

Senators Michael Bennet (D-Colorado) and John Cornyn (R-Texas) have reintroduced the 

Increasing Access to Biosimilars Act to Congress

 is to boost competition and increase incentives for providers to prescribe biosimilars over their more expensive reference agents.

 presented at the American Academy of Dermatology (AAD) annual meeting examined the effects of switching from reference ustekinumab and adalimumab to biosimilar versions in patients with different types of psoriasis.

 7% overall last year, including a 15% spike in biosimilar sales, according to the company’s 

 for the fourth quarter (Q4) and full year (FY) 2023.

Here are the top 5 biosimilar articles for the week of March 25, 2024. 