Justina Petrullo

Stephen Hanauer, MD, professor of medicine, Feinberg School of Medicine, Northwestern University, comments on concerning data from Cardinal Health and Spherix Global Insights regarding the potential growth of the US adalimumab market, including providers’ views on interchangeability and payers’ influence on utilization.

, a Cardinal Health report found that over 60% of providers intend to only prescribe adalimumab biosimilars that have an interchangeability designation, indicating that providers consider interchangeability to be a significant safety identifier, despite this not being what the label means. Why do you think providers feels this way, and what more is needed to clarify the meaning of interchangeability?

Well, providers have been swayed over a number of years from a variety of different directions. Initially, the originators swayed providers by putting doubt into their mind regarding how similar a biosimilar really is. And in particular, as you mentioned earlier, in the absence of trials within inflammatory bowel disease, so there's been a sense of doubt that has been placed for many years. 

But the reality is that it's not going to be up to the provider. Because if a third-party payer decides to provide a biosimilar at a substantially lower cost to the patient, they're not likely going to pay the difference for what the biosimilar would cost them, which is usually nothing. Remember, patients are usually paying about $5 a month for adalimumab nowadays. If the patients actually have to pay for the drug, there's going to be a substantial cost difference.

 found that despite high awareness of adalimumab biosimilars options, uptake has been low so far. What more needs to be done to improve provider willingness to prescribe these agents?

It's not the willingness to prescribe, it's that the originator has negotiated pricing that is still favorable to third-party payers. Hence, the need to accept a biosimilar has been less than anticipated. But as we've seen, this will change over time as there is greater and greater acceptance and the multiple biosimilars will ultimately bring the cost of adalimumab down.

Videos

Stephen Hanauer, MD, professor of medicine, Feinberg School of Medicine, Northwestern University, reflects on data concerning the potential for adalimumab biosimilars to gain significant market share.

Dr Stephen Hanauer Gives Insight Into Growing US Adalimumab Market

There are many steps that health systems can take to prevent the nocebo effect when transitioning patients from Humira (reference adalimumab) to an adalimumab biosimilar, according to Stephen Hanauer, MD, professor of medicine, Feinberg School of Medicine, Northwestern University.

Can you discuss the importance of pharmacovigilance in populations with Crohn disease and ulcerative colitis since there haven’t been many studies evaluating adalimumab biosimilars in these patients?

Pharmacovigilance studies for any specific biosimilar are going to be quite a challenge, because it's likely that, [for example,] third party A will pick biosimilar 1 for a year and then, because of changing costs may pick biosimilar 2 or 3. So I believe in this environment. There's going to be a lot of switching between the different agents, which means that pharmacovigilance of a single agent is going to be much more challenging.

How do you think the Crohn disease patient community is responding to adalimumab biosimilar options and the potential for more nonmedical switching from the reference agent to a biosimilar? Are you fearful of the nocebo effect for these patients?

That's the most challenging question, because patients see the medicine as their medicine; for instance, "my Humira." One of the worst things that you can do in social psychology is take something away from an individual. And if you're taking away "their Humira" and substituting something else, they perceive that as not necessarily being good—often as being bad.

So, we need to be able to circumvent that concept that feeds into the nocebo effect, which is going to be accomplished by having the biosimilar company not just having a biosimilar product but having it perform and be administered in the same or easier ways [as the reference product.] For instance, there may be better injectors available for individuals that might be easier [to use]. It will be important for patients who are using citrate-free products to have a citrate-free formulation available to obviate worsening symptoms with injections or injection site reactions.

And then all the other services that have come with the originator, with Humira from AbbVie, need to be replicated for each and every biosimilar for it to be acceptable to the patient. So, the presence of having nurse navigators or ambassadors present, for having assistance programs available, and all the other services to patients are really going to be needed in order to prevent this nocebo effect.

Another important concept is cognitive dissonance. In other words, the more effort somebody puts into something, the more perceived benefit, and that includes costs. So that's why if someone sees 2 identical sweaters and 1 cost more than the other, they tend to like it better. And so substituting a less costly [option] may be perceived as less beneficial or less effective.

Stephen Hanauer, MD, professor of medicine, Feinberg School of Medicine, Northwestern University, discusses why providers need to be wary when deciding whether patients with Crohn disease should switch from Humira (reference adalimumab) to an adalimumab biosimilar.

Dr Stephen Hanauer Weighs In on Pharmacovigilence, Nonmedical Switching in Crohn Disease

Stephen Hanauer, MD, professor of medicine, Feinberg School of Medicine, Northwestern University, highlights the importance of his study comparing an adalimumab (Cyltezo) with the refrence product (Humira) patients with gastroenterology conditions.

What role can your trial play in improving patient and provider confidence in using adalimumab biosimilars for Crohn disease and ulcerative colitis?

The study actually provides additional reassurance regarding the biosimilarity and the potential of patients switching from either the [reference product] to the biosimilar or substituting the biosimilar from the onset.

Why are more clinical studies on anti-TNF [tumor necrosis factor] medications in gastroenterology conditions needed and how can providers and health systems be better advocates for these types of trials? 

Firstly, there still is room for improvement in efficacy within the TNF class. We're not getting 100% remission rates and we know that remission rates can be improved with the addition of immunomodulators for instance, or dose escalation in some situations. In addition, we are seeing newer TNF formulations—for instance, of subcutaneous infliximab—as a maintenance therapy. So, as additional biosimilars are coming out, we also have additional new products of the same class that are being evaluated and offer patients different opportunities, for instance, of intravenous versus subcutaneous formulations at different intervals.

Stephen Hanauer, MD, professor of medicine, Feinberg School of Medicine, Northwestern University, shares why his study comparing the safety and efficacy of Cyltezo, an adalimumab biosimilar, with the originator (Humira) matters for patients with gastroenertology conditions.

Dr Stephen Hanauer: Why More Studies Assessing Adalimumab Biosimilars in Gastro Conditions Are Needed

Hi, I’m Justina Petrullo for The Center for Biosimilars

, your resource for clinical, regulatory, business, and policy news in the rapidly changing world of biosimilars.

Here are the top 5 biosimilar articles for the week of October 9, 2023.

 he's filed to the FDA as well as changes he believes are needed to propel the biosimilar industry into the future, including calling on biosimilar manufacturers to help.

Number 4: At EURETINA 2023, Samsung Bioepis shared 

 on its aflibercept biosimilar candidate, demonstrating that the product is as safe and effective as the originator (Eylea).

Number 3: Boehringer Ingelheim (BI) launched an unbranded version of its 

 Alvotech and Kashiv Biosciences partnered for an omalizumab biosimilar candidate; the FDA issued a complete response letter (CRL) for Biocon’s insulin aspart biosimilar.

 developed by Biogen, will be used to treat rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, and systemic juvenile idiopathic arthritis.

Number 1: Pfizer’s Abrilada (adalimumab-afzb) became the 

second biosimilar referencing Humira (adalimumab)

 to receive an interchangeable designation. The new label is intended to expand patient access to biosimilars.

To read all of these articles and more, visit 

The Top 5 Biosimilar Articles for the Week of October 9

Image credit: Chinnapong - stock.adobe.com

No difference was found in the safety profiles or immunogenicity rates in patients who were 

 and those who stayed on a reference biologic or biosimilar, according to the first systematic review using statistical methods to address switching risk in patients between reference biologics and biosimilars in 

Biosimilars are progressively available for the treatment of multiple severe disorders, but some concerns remain about switching a patient to a biosimilar whose condition is stable on the reference biologic.

Researchers analyzed the occurrence of safety events after a switch to or from a biosimilar and its reference biologic in all identified controlled clinical studies that encompassed a biosimilar approved by the FDA.

Growing the availability and use of biosimilars is an important public health strategy for decreasing drug costs and increasing the accessibility of biological products to underserved populations.

Randomized controlled studies and extension studies with a switch treatment period (STP) to or from a biosimilar and its reference biologic were distinguished from publicly available information sustained by the FDA. These findings were strengthened with data from peer reviewed publications that held information not captured in FDA reviews. A total of 44 STPs were recognized from 31 distinctive studies for 21 different biosimilars.


PRISMA guidelines to extract and synthesize the data were followed. Meta-analysis was undertaken to estimate the overall risk difference across studies. Patients who were switched to or from a biosimilar and its reference biologic make up a cohort of 5,252 patients.

Additionally, deaths, serious adverse events, and treatment discontinuation included in safety data illustrated an overall risk difference of -0.00, 0.00, -0.00 across STPs, respectively. Similar incidence of antidrug antibodies and neutralizing antibodies in patients within a STP who were switched to or from a biosimilar to its reference biologic and patients who were not switched were displayed by immunogenicity data. Also, immune-related adverse events like anaphylaxis, hypersensitivity reactions, and injection site reactions were similar in switched and non-switched patients.

Antidrug antibodies and neutralizing bodies showed comparable incidence between No Switch and Switch arms. The study participants in the STPs are symbolic of patients who would be switched to or from a biosimilar and its reference product and mirror actual use. This outcome is constant with empiric evidence and descriptive reviews of switching biosimilars and referencing biologics.

“The findings in this report raise several timely questions regarding the data needed to support approval of biosimilars and how to address regulatory requirements unique to the [Biologics Price Competition and Innovation Act] for the 'interchangeable' designation,” said the researchers.

 allow for pharmacists to substitute a reference product for a biosimilar without needing to obtain permission from a provider. It's intended to increase access to biosimilars and shorten wait times for patients to get their prescriptions. However, many experts 

 whether designations like this should be needed.

Also, the findings supported efforts to decrease the regulatory burden of switching studies as the default approach for acknowledging the switching standard for the interchangeable designation.

This study also supports the reassessment of the need for switches included in clinical studies for candidate biosimilars since an approved biosimilar will be analytically highly similar to its reference product. As familiarity and the support for biosimilar approvals grows, the amount and types of clinical data consistently performed as part of biosimilar development may be decreased, which would also decrease the time and cost of development.

Some limitations were present in this review, including the small number of patients in the safety evaluations from some source material. There were fewer patients in some STPs, but these differences in STP sample size had been taken into consideration in the meta-analysis.

This study acknowledges one of the concerns of the medical community about the safety of switching between reference products and corresponding biosimilar products.

“Data driven materials such as those contained in this report will facilitate efforts to streamline biosimilar development and achieve the full promise of biosimilars,” concluded the researchers.

Herndon TM, Ausin C, Brahme NN, et al. Safety outcomes when switching between biosimilars and reference biologics: a systematic review and meta-analysis. 

. Published online October 3, 2023. doi:10.1371/journal.pone.0292231

Articles

No safety or immunogenicity differences were found in patients who switched to a biosimilar and those who continued on a reference biologic or biosimilar.

Review: No Safety, Efficacy Issues Found in Patients Who Switched From Originators to Biosimilars

Stephen Hanauer, MD, professor of medicine, Feinberg School of Medicine, Northwestern University, emphasized that although adalimumab biosimilars are new to gastroenterologists, this is not their first experience with anti–tumor necrosis factor (TNF) agents.

 that demonstrated the safety and efficacy of an adalimumab biosimilar (Cyltezo) in patients with advanced Crohn disease. As of October 2023, it is the only study assessing an adalimumab biosimilar in patients with inflammatory bowel disease, which is an umbrella term for Crohn disease and ulcerative colitis. 

With 8 adalimumab biosimilars now on the US market, how are gastroenterologists reacting to these new products and are there concerns about extrapolated indications for inflammatory bowel disease?

The 8 adalimumab biosimilars are not gastroenterologists' first experience with biosimilars actually. We've had some experience with infliximab biosimilars over the past several years. In reality, it's unlikely that most gastroenterologists are going to prescribe a specific biosimilar because they're so much dependent on third party payers and their individual preferences. So, I think it's more likely that gastroenterologists are going to order for instance, Humira [reference adalimumab] and accepted alternative biosimilar or use the term "adalimumab" and again, accept biosimilars.

How important is it to have trials for adalimumab products and other anti-TNF biosimilars tested in patients with gastroenterology conditions, especially when most of the other trials for these products have only been tested in rheumatoid arthritis and psoriatic arthritis populations?

Again, gastroenterologists, overall have accepted the regulations for biosimilars that allow for extrapolation. However, having individual studies with specific biosimilars do provide a little bit more reassurance, perhaps, that the performance is going to be as [similar to the reference product] as anticipated.

Stephen Hanauer, MD, professor of medicine, Feinberg School of Medicine, Northwestern University, explained the initial experience gastroenterologists have had with anti–tumor necrosis factor biosimilars and how new adalimumab biosimilars will impact the space.

Dr Stephen Hanauer Welcomes Adalimumab Biosimilars to the Gastroenterology Space

Hi, I’m Justina Petrullo for The Center for Biosimilars®, your resource for clinical, regulatory, business, and policy news in the rapidly changing world of biosimilars.

Here are the top 5 biosimilar articles for the week of October 2nd, 2023.

Number 5: Compared with other biologics frequently used in China for moderate-to-severe psoriasis, 

 of its ustekinumab biosimilar referencing Stelara in Japan for autoimmune conditions. The company also released an update on the US filing for its adalimumab biosimilar.

Number 3: With the European Commission's (EC) 

, Europe received its first natalizumab biosimilar and first biosimilar to treat multiple sclerosis (MS), while Coherus Biosciences received a complete response letter (CRL) for its biosimilar for Neulasta Onpro.

Number 2: Patients with inflammatory bowel disease who underwent a switch from reference infliximab to a biosimilar and then back to the originator were 

 their treatment than patients who underwent a single switch from the originator to a biosimilar.

Number 1: Drug maker payments to ophthalmologists were associated with the choice of 

 for age-related macular degeneration (ARMD) that could increase Medicare costs, but biosimilars could help.

Here are the top 5 biosimilar articles for the week of October 2, 2023.

The Top 5 Biosimilar Articles for the Week of October 2

On this episode, we will discuss several regulatory updates from around the globe, including some European and Japanese approvals, the FDA’s 2-day workshop on the present science behind clinical efficacy testing for biosimilars, and streamlining biosimilar development.

House Committee Hearing Addresses PBMs, Anticompetitive Drug Pricing Tactics

Part 2: FDA Workshop Shares Manufacturer Perspective on the Value of Clinical Efficacy Testing

Part 1: FDA Workshop Highlights Global Regulatory View on Biosimilar Development

Part 3: BioRationality—FDA Webinar on Biosimilars Efficacy Testing Marks Major Step Forward

Alvotech’s Stelara Biosimilar Approved in Japan

EC Approves First MS Biosimilar; Coherus Receives CRL for Neulasta Onpro Competitor

European Commission Approves First Aflibercept Biosimilar

Regulatory Updates From Around the Globe Provide Hope for Biosimilars

Podcasts

On this episode, we discuss several regulatory updates from around the globe, including some European and Japanese approvals, the FDA’s 2-day workshop on the present science behind clinical efficacy testing for biosimilars, and streamlining biosimilar development.

Biosimilars Regulatory Roundup for September 2023—Podcast Edition

Here are the top 5 biosimilar articles for the week of September 25th, 2023.

Number 5: Although removing the requirement for clinical efficacy testing for biosimilar approval would reduce development costs of biosimilars, representatives from several biosimilar manufacturers argued in the 

second day of the FDA’s development workshop

 that clinical outcomes will not be affected.

Number 4: Drug maker payments to ophthalmologists were associated with the choice of higher-cost therapies for age-related macular degeneration (ARMD) that could increase Medicare costs, but 

Number 3: A study evaluating the real-world impact of treating patients with inflammatory bowel disease (IBD) with an adalimumab biosimilar found that providing patient questionnaires early can be useful for 

Number 2: The European Commission approved the 

, which will be used to treat patients with age-related macular degeneration and diabetic macular edema.

 of a 3-part series, Sarfaraz K. Niazi, PhD, gave his take on the FDA's recent workshop dedicated to streamlining biosimilar development and his opinion on what the industry can learn from the webinar presenters.

Here are the top 5 biosimilar articles for the week of September 25, 2023.

The Top 5 Biosimilar Articles for the Week of September 25

Secukinumab is the most cost-effective treatment option for patients with moderate-to-severe 

 compared with other biologics frequently used from the perspective of the Chinese health care system, according to a study from 

Currently, there are no approved secukinumab (Cosentyx) biosimilars, although some are in development. Bio-Thera Solutions is conducting Phase 3 trials for the clinical development of a secukinumab biosimilar for plaque psoriasis as of September 11, 2023, according to 

, and at the time Bio-Thera Solutions stated that it will file for regulatory approval for all indications of the reference product in the European Union, United Kingdom, China, and United States upon completion of the trial. The patent on the 

Patients with moderate-to-severe psoriasis usually need treatment throughout their life, and psoriasis presents a large economic burden on patients and their families in China. The total yearly expenditure because of psoriasis accounts for approximately 20.0% of patients’ income and cumulates into a yearly hospitalization rate of 21.3%, 15.0 days of sick leave, and a 37.0% rate of unemployment.

First, the study evaluated the cost effectiveness of secukinumab compared with other biologics (adalimumab, infliximab, ustekinumab, ixekizumab, guselkumab, and etanercept biosimilar [Yisaipu]) for the treatment of moderate-to-severe plaque psoriasis from the perspective of the Chinese health care system.

A decision-tree (first year)/Markov model (subsequent years), with a yearly cycle, was implemented over a lifetime. The Psoriasis Area and Severity Index (PASI) response rate at week 16 was utilized for treatment response. Efficacy inputs were collected from a mixed-treatment comparison conducted using randomized controlled trial data.

Other clinical inputs (like adverse events, dropout, and mortality rates), utility weights, and costs were originated from published literature and local Chinese sources. Costs and outcomes were discounted at 5% per annum. Model outcomes contained quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were administered to test result robustness.

It was found that secukinumab produced the highest QALYs (12.334) against all comparators at a lifetime cost of ¥231,477 (approximately $31,661) for patients with moderate-to-severe psoriasis. Secukinumab overpowered (higher QALYs at lower costs) all other biologics except ixekizumab in this population. Ixekizumab acquired slightly lower costs (¥228,320 [$31,229]) but obtained lesser QALYs (12.284), compared with secukinumab. So, secukinumab was a cost-effective treatment than ixekizumab at a willingness-to-pay (WTP) threshold of ¥257,094 ($35,164) per QALY acquired.

“In the one-way sensitivity analysis, base-case results were most sensitive to changes in the PASI response at 16 weeks and year 2+ dropout rates,” continued the researchers.

Additionally, the researchers found that secukinumab was a cost-effective treatment option versus adalimumab, infliximab, ustekinumab, ixekizumab, guselkumab, and etanercept biosimilar (Yisapu) among patients with moderate-to-severe psoriasis over a lifetime.

“The results of base-case analysis were most sensitive to changes in the PASI response at 16 weeks and year 2+ dropout rates for all treatment comparisons,” said the researchers.

Results similar to base-case analysis validating the cost-effectiveness of secukinumab were also seen in the alternative scenario analysis.

To the researchers’ knowledge, this is the first comprehensive economic evaluation comparing the costs and benefits (QALYs) linked with secukinumab compared to other commonly used biologics in the Chinese health care setting.

Some limitations were present in this study. The model used short-term efficacy data to project lifetime efficacy, stemming from the network meta-analysis that was limited to week 16 because of crossover of treatment arms past week 12 or week 16. Also, treatment sequencing was present, because the current analysis was restricted to first-line biologic treatment only.

“This cost-effectiveness analysis demonstrated that secukinumab is the most cost-effective treatment option compared with other commonly used biologics (adalimumab, infliximab, ustekinumab, ixekizumab, guselkumab, and Yisaipu) for moderate-to-severe plaque psoriasis in China over a lifetime horizon,” concluded the researchers.

 Cost-effectiveness of secukinumab versus other biologics in the treatment of moderate-to-severe plaque psoriasis: the Chinese healthcare system perspective. 

 Published online September 23, 2023. doi:10.1007/s13555-023-01041-8

2. Secukinumab biosimilar by bio-thera Solutions for plaque psoriasis (psoriasis vulgaris): likelihood of approval. pharmaceutical technology. Published September 11, 2023. Accessed September 27, 2023. 

https://www.pharmaceutical-technology.com/data-insights/secukinumab-biosimilar-bio-thera-solutions-plaque-psoriasis-psoriasis-vulgaris-likelihood-of-approval/#:~:text=Secukinumab%20biosimilar%20overview,is%20administered%20through%20subcutaneous%20route

3. Higgins-Dunn N. The top 15 blockbuster patent expirations coming this decade. Fierce Pharma. Published July 12, 2021. Accessed September 27, 2023. 

https://www.fiercepharma.com/special-report/top-15-blockbuster-patent-expirations-coming-decade

Compared with other biologics frequently used in China for moderate-to-severe psoriasis, secukinumab is the most cost-effective treatment option.