Cameron Santoro is an associate editor for The Center for Biosimilars

Cameron Santoro

The Top 5 Biosimilar Articles for the Week of May 6, 2024. 

 showed some misalignment in payer coverage of granulocyte colony-stimulating factor (G-CSF) biosimilars, highlighting that while filgrastim biosimilars are often favored over the originator, reference pegfilgrastim still dominates over its biosimilars.

The FDA approved a high-concentration, citrate-free version of Boehringer Ingelheim’s 

, making it the second high-concentration adalimumab biosimilar to have an interchangeability designation.

 The approval marks the sixth for a biosimilar referencing 

 for the treatment of HER2-positive breast and gastric cancers.

 During her presentation during Festival of Biologics USA, 

, PharmD, director of formulary management at Sutter Health, gave an overview of current challenges and opportunities for the biosimilar market and offered calls to action for multiple stakeholders.

 summarizes the product attributes of reference and biosimilar adalimumab products, such as formulation with or without citrate, delivery volume, and needle gauge, relevant to patients’ experience of injection-site pain.

To read all of these articles and more, visit 

Videos

Here are the top 5 biosimilar articles for the week of May 6, 2024. 

The Top 5 Biosimilar Articles for the Week of May 6

Health equity chart. Image Credit: leowolfert - stock.adobe.com

Over the past decade, biosimilars have emerged as a transformative force within the pharmaceutical landscape. Initially introduced in Europe, they have steadily gained traction in the United States, proposing an increased patient access to life-saving medications at lower costs.

Biosimilar development hinges on rigorous scientific comparisons. Extensive data analysis, including clinical pharmacokinetic similarities, forms the backbone of these evaluations. Biosimilars undergo meticulous scrutiny to ensure they match the efficacy, safety, and immunogenicity profile of their brand name counterparts.

 Ultimately, FDA approval signifies that no clinically meaningful differences exist between the biosimilar and the originator biologic drug.

However, a concerning trend has emerged, with clinician familiarity of biosimilars falling below expectations, hindering their prescription rates. Given their cost effectiveness and near identical characteristics to brand name drugs, why are biosimilars not achieving the market adoption they deserve?

This marks the first installment of a 2-part series, brought to you by The Center for Biosimilars

. We will delve into the potential of biosimilars to empower underserved communities while dissecting the obstacles that currently prevent them from accessing these affordable treatments.

Our series, titled "Unlocking the Potential of Biosimilars to Improve Health Equity," will shed light on the significant knowledge gaps within the medical field. The 2-part series kicks off by exploring medical mistrust in underserved communities and the knowledge gaps created by critical barriers faced by both patients and healthcare professionals. In part 2, focus is shifted on the role of payers, pharmacy benefit managers, and the financial incentives that influence prescription choices.

Biosimilars hold promise for affordable treatment options while maintaining the same safety and efficacy compared with their originators, but barriers from pharmacy, physician, and insurance groups limit patient access to health equity, especially for underserved communities.

Biosimilars: Affordable, Effective Treatments

Patient access to biosimilars allows earlier treatment access which can result in improved outcomes by controlling symptoms and reducing symptom severity. Biosimilar sales are typically priced 11% to 45% lower than originators and promote considerable savings for eligible patients.

 Since the Biologics Price Competition and Innovation Act (BPCIA) of 2009 was passed, biosimilars have generated $37 billion in savings, despite slow uptake in some markets.

As more biosimilars launch and experience increased uptake, losses for originator products are expected to rise from $111 billion to $192 billion by the end of 2028.

 In its Global Use of Medicines report, the IQVIA Institute for Human Data Science estimated the spending on reference products will decrease $39.5 billion over the next 5 years thanks to biosimilar competition. The future holds significant promise for biosimilars with global use potentially growing to 3.8 trillion daily doses by 2028, an overall 400 million increase compared with 2023.

In an interview with The Center for Biosimilars, Robert Popovian, Pharm.D, MS, a health economist, and founder of Conquest Advisors, stated, “We need to address benefit design. Over the last 10 years there’s been coinsurances and deductibles introduced in the benefit design for biopharmaceuticals. Because of that, [drug prices] are a little bit of an unknown.”

While the potential advantages of biosimilars are undeniable, realizing their full impact can be a complex process with the current policies in place. To ensure biosimilars can provide all patients with adequate care and savings, stakeholders will need to address some of the challenges that exist and propose potential solutions for navigating them effectively.

In the US, people without health insurance often have trouble accessing affordable health care. One study found non-White populations were 70% more likely to not have health insurance in comparison to their Caucasian counterparts.

 In addition, geographic areas that have limited access to doctor’s offices and other facilities had higher populations of non-White communities. Black families were also twice as likely as White families to live in poverty, making an average of $52,860 yearly income compared with $81,060 for non-Hispanic White annual income.

White people living among rural populations are also affected by inadequate health care at higher rates compared with White people living in urban areas. With one-fifth of the American population occupying rural regions, local hospitals and access to care are limited.

 From 2013 to 2020, about 4% of rural hospitals closed in the US, leaving residents with 20 miles to 40 miles of travel.

Biosimilars are intended to offer effective treatments to various communities and illnesses no matter their financial status. With the emergence of self-injectable and on-body drug administration options for biosimilars, patients can reduce their dependence on hospital facilities and drug delivery related health care costs.

Subcutaneous administration is significantly beneficial by making drug delivery less time consuming for patients from underserved communities as many of these patients with conditions requiring biologic therapies are unemployed or working part-time based on the severity of their condition. This option helps patients living further from the hospital or those who do not have a reliable means of travel. Minimizing travel can also reduce the risk of exposure to hospital-acquired infections among patients and any accompanying companions.

Considering the financial inequalities non-White communities face, biosimilar competition proposes lower costs for the whole market, including the reference product. Systemic evidence found competition has resulted in marginal price decreases, with biosimilars being priced only about 30% less than their originators.

 Overall, this represents an average discount of $665 off the typical price. Biosimilars offer the potential for significant cost savings, with research suggesting a 4.3 times higher savings rate compared with generics. However, the question of whether these savings translate directly to patient affordability remains complex and will be explored further in part 2 of this series.

Medical Mistrust Leads to Treatment Hesitancy

Biosimilars have the potential to promote greater accessibility and affordability to non-White populations, but current access is limited due to factors like medical mistrust and racial inequalities in health care. Historically, underserved populations endured various forms of medical malpractice, specifically Black people. Ultimately, this has led to loss of trust among non-White communities, racial prejudices in the health care sector, and a neglect in treatment for these populations.

In a Canadian study, Black patients were found to be less likely to receive biologic treatment for several medical conditions.

 The US sees similar patterns as there is a lot of medical mistrust among Black communities, stemming from a long history of unethical medical practices that have harmed them. Some of the most prominent, documented forms of medical malpractice were conducted on enslaved women by James Marion Sims, MD, between 1845 to 1849, who is now referred to as “the father of gynecology.”

 Sims operated on his participants, often enrolled by their enslavers, without anesthesia because he was under the racist belief that “Black people did not feel pain.”

Almost 100 years later, unethical medical malpractice continued throughout the 1930s, notably the Tuskegee experiment, which is often cited as a major stimulus for the mistrust of medical advances among Black populations.

 Similarly to the enslaved women, some 600 African American participants did not express informed consent and were not offered treatment if infected with syphilis, despite medical advancements becoming widely available.

Additionally, the little representation of Black and Indigenous health care workers is not nearly equivalent to other races. Unequal access to quality health care and a history of mistreatment has led to a gap in trust when it comes to new medical developments for underserved populations.

The mistrust non-White communities have towards health care professionals contributes to biologic treatment hesitancy. In a US study, results found higher levels of unfamiliarity of biologic therapies in Black patients compared with White patients.

 The knowledge gaps non-White communities have towards biologics or false information is largely due to the lack of comfort they have in asking health care professionals and trusting the feedback they receive.

Racial inequalities Black patients experience resulted in the decreased likelihood they would receive reference trastuzumab for breast cancer treatment. Trastuzumab, a biologic rapidly growing in US cancer care, holds potential for the reduction of health care inequalities but often dismisses marginalized communities in study populations.

Clinical trials aim to prove the safety and effectiveness of biosimilars, but the health care system has low participation of non-White populations, furthering their medical mistrust. A study found only 2.6% of global cancer clinical trials included Black participants.

 Aside from general representation, demographic variety is important because it reveals any inter-ethnic differences in drug responses and metabolism. This lack of representation in clinical trials can only be addressed if there is a significant shift in how health care builds trust with minority communities.

Additionally, the lack of transparency pharmacy benefit managers (PBMs) have with patients furthers this medical mistrust. The 3 PBMs that control around 80% of the market are CVS Caremark, Express Scripts, and Optum Rx, which are all operated by major health insurers and/or owned by a pharmacy.

 These PBMs are ultimately negotiating with themselves or 1 of their competitors to create financial incentives that benefit themselves while negatively impacting patients.

Chiara Gasteiger, PhD, of Stanford University’s Mind and Body Lab researching as a postdoctoral scholar explained in an interview, “To combat trust issues among patients, providers, and physicians, there needs to be more transparency on the role of PBMs [pharmacy benefit managers], their negotiation processes and disclosure of rebate retentions to build trust and understanding from stakeholders, health care providers, and policymakers. Existing regulations should also ensure that PBMs comply with laws that protect patients and encourage fair pricing.”

Transparency around PBMs is crucial and these efforts must be coupled with addressing the everyday challenges faced by patients that create mistrust, particularly in underserved communities. Bureautic hurdles, such as language or health literacy, disproportionately affect underserved communities in several ways. A 2020 survey on race and health revealed 20% of both Black and Hispanic adults reported unfair treatment based on race or ethnicity in health care within the past year.

 In a separate survey from 2021, 24% of Hispanic adults expressed it was “very” or “somewhat difficult” to find a physician that was able to explain things in a way they could easily understand.

Underserved communities, burdened by limited advocacy, finances, and often low health literacy, struggle to access essential medications. Biosimilars, offering comparable treatments at lower costs, can empower these communities towards better health outcomes.

Popovian described a study he participated in where he found, “it's not just health literacy and education of patients. It's also health literacy and education of health care providers,” in reference to the existing knowledge gaps surrounding biosimilars.

Further communication between physicians and patients would allow underserved, underrepresented communities to establish a level of trust with health care systems. Language barriers include complicated medical terminology, differing dialects between patient and physicians, and providers often being unable to communicate in non-native English speakers’ primary languages. 

Gasteiger suggested, “Information should be presented in a language and communication style that aligns with the patient’s health literacy and cultural norms, including the option to have a support person present.” It is up to health care systems to work with the patient and their caregivers on the status and severity of the patient’s condition and potential treatment options.

Gasteiger argued that physicians building rapport with their patients helps establish trust, enabling open dialogue about concerns, especially when providers are transparent about funding limits. Bridging knowledge gaps and addressing the evolving needs of each unique patient and their families must be tailored through collaboration, reiteration, and flexibility among providers.

She suggested “Transparent patient and family-centered communication and shared decision-making should be encouraged to build trust and promote patient autonomy. Small nudges can also be used to encourage more positive perceptions of biosimilars, such as through positive message framing and carefully balancing risk benefit information.

With the little representation of most underserved communities, health care providers can seem intimidating to certain patients, ultimately preventing them from participating in the decision-making process. Furthermore, increased access to information in the modern age leads to an increased risk of spreading misinformation, leaving vulnerable populations at risk for false theory consumption.

“It is important to empower patients to identify misinformation and provide credible supportive material. Implementing more guidelines for media reporting on biosimilars could further help to combat misinformation,” Gasteiger stated.

Gaining multiple opinions and expanding research upon treatments can be beneficial in educating patients and physicians. The FDA website has multimedia educational resources on biosimilars and interchangeable products for patients, caregivers, and health care providers.

 These materials are available in multiple formats and languages. Fortunately, some of the educational resources are also offered through videos, an important factor for populations with low literacy rates.

“More education, such as on testing and manufacturing, needs to be integrated into medical training curriculums and all providers should have access to comprehensive training programs that are regularly updated with new designations, guidelines, and policies,” Gasteiger suggested as a solution.

Popovian commented, “We need to do quite a bit of education but it's super important to be able to do it both on the health care professional side and on the patient side. It's also important to understand that especially that education is important for patients on chronic care medicines that they've been taking for very long.”

Through collaborative communication, culturally sensitive education, and a commitment to shared decision-making, health care providers can unlock the potential of biosimilars for underserved communities, empowering patients to make informed choices about their health.

1. Shubow S, Sun Q, Nguyen Phan AL, et al. Prescriber perspectives on biosimilar adoption and potential role of clinical pharmacology: A workshop summary. 

. 2023;113(1):37-49. doi:10.1002/cpt.2765

2. Jeremias S. IQVIA predicts biosimilar, generic competition will cost originators $192 billion by 2028. Drug Topics. January 19, 2024. Accessed March 29, 2024. https://www.drugtopics.com/view/iqvia-predicts-biosimilar-generic-competition-will-cost-originators-192-billion-by-2028

3. Health O of M. Advancing better health through better understanding for black and african american communities: Health literacy, health care access, and culturally appropriate care 2024 reading list. www.hhs.gov.

January 30, 2024. Accessed March 29, 2024. https://www.hhs.gov/black-history-month/readinglist/index.html#:~:text=Black%20households%20are%20twice%20as

4.Hundrup A. Why health care is harder to access in rural America. U.S. GAO. May 16, 2023. Accessed April 25, 2024. https://www.gao.gov/blog/why-health-care-harder-access-rural-america

5.Jonaitis L, Marković S, Farkas K, et al. Intravenous versus subcutaneous delivery of biotherapeutics in IBD: an expert's and patient's perspective. 

. 2021;15(17):25. doi:10.1186/s12919-021-00230-7

6. Goldman D, Philipson T. Biosimilars competition helps patients more than generic competition. STAT. October 8, 2021. Accessed March 29, 2024. https://www.statnews.com/2021/10/08/biosimilars-competition-helps-patients-more-than-generic-competition/

7. Akuffo-Addo E, Udounwa T, Chan J, Cauchi L. Exploring biologic treatment hesitancy among black and indigenous populations in Canada: a review. 

. 2023;10(2):942-951. doi:10.1007/s40615-022-01282-x

8. Holland B. The “father of modern gynecology” performed shocking experiments on slaves. History.com. Published December 4, 2018. Accessed March 29, 2024. https://www.history.com/news/the-father-of-modern-gynecology-performed-shocking-experiments-on-slaves

9. Petrullo J. Biosimilars can expand treatment access for traditionally excluded communities. Center for Biosimilars. July 18, 2023. Accessed March 29, 2024. https://www.centerforbiosimilars.com/view/biosimilars-may-expand-treatment-access-for-traditionally-excluded-communities

10. Hearing wrap up: Pharmacy benefit managers push anticompetitive drug pricing tactics to line their own pockets - United States house committee on oversight and accountability. Press release. United States House Committee on Oversight and Accountability; October 2, 2023. Accessed April 25, 2024. https://oversight.house.gov/release/hearing-wrap-up-pharmacy-benefit-managers-push-anticompetitive-drug-pricing-tactics-to-line-their-own-pockets%EF%BF%BC/#:~:text=But%20that%20environment%20of%20competition,is%20owned%2C%20by%20a%20pharmacy.

11. Ndugga N, Artiga S. Disparities in health and health care: 5 key questions and answers. Kaiser Family Foundation. April 21, 2023. Accessed March 29, 2024. https://www.kff.org/racial-equity-and-health-policy/issue-brief/disparities-in-health-and-health-care-5-key-question-and-answers/

12. Multimedia Education Materials, Biosimilars. FDA. 2024. Accessed April 1, 2024. https://www.fda.gov/drugs/biosimilars/multimedia-education-materials-biosimilars#For%20PatientsDD

Articles

Biosimilars offer a promising path to affordable, effective treatment, but barriers remain for underserved communities. This 2-part series explores the potential of biosimilars to improve health equity while addressing the obstacles that currently prevent access.

Part 1: Unlocking the Potential of Biosimilars to Improve Health Equity

The Top 5 Biosimilar Articles for the Week of April 29. 

 Despite current challenges in biosimilar market growth due to stakeholder disagreements, a recent commentary proposes that applying 

 can achieve widespread biosimilar market uptake by fostering collaboration for long-term benefits.

 (trastuzumab-strf; HLX02), for the treatment of HER2-positive breast cancer. The approval marks the 

 for a biosimilar referencing Herceptin (trastuzumab) and first overall for the company in the US.

 annual meeting explore how an interchangeable insulin glargine biosimilar plays into Medicaid budgets and the top factors driving access to biosimilars.

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

 summarized the totality of evidence supporting the approval of the 

 (Hyrimoz; Sandoz) in the United States and Europe.

Here are the top 5 biosimilar articles for the week of April 29, 2024. 

The Top 5 Biosimilar Articles for the Week of April 29

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.

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.

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

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

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