Justina Petrullo

The American College of Rheumatology (ACR) vehemently supports the availability of safe and effective treatments at the lowest cost possible to patients in a position statement presented by the Committee on Rheumatologic Care.

Following this introductory statement, the ACR emphasizes the necessity of sound science and the consideration of 6 observations and guiding principles that they outline in the position statement:

They recognize that due to the size, complexity, and heterogeneity of biologics, and therefore biosimilars, more scrutiny is needed in the evaluation of biosimilars compared with what might be needed for small molecule generics.

The ACR emphasizes the need for clinical data to make sure biosimilars are safe and effective, in addition to the necessary studies inherent to drug manufacturing. Additionally, they highlight that a record of long-term data on each biosimilar is necessary to monitor for less common but still critical adverse events.

They speak on the necessity of long-term monitoring for children and adults: “Postmarketing surveillance studies are needed in children, as well as adults, as toxicities and long-term sequelae may be different in these disparate populations. The Best Pharmaceuticals for Children Act, which reauthorizes the pediatric studies provision of the FDA Modernization and Accountability Act to improve safety and efficacy of pharmaceuticals for children, should apply to biosimilars.”

They call for more clear FDA labels (package inserts) to indicate if a biosimilar is interchangeable with the reference biologic, and that these labels should clarify all approved biosimilar indications. Also, they require specification on if the data for the indication is taken from studies of the biosimilar or the reference biopharmaceutical.

Additionally, if health care providers choose a medication that has a biosimilar option for a patient, the ACR supports the use of a biosimilar first.

In position 6, the ACR highlights their opposition to forced biosimilar switching by insurers:

“In patients on established therapy, the final decision to switch from a reference product to a biosimilar should rest with the prescriber and the patient. The ACR opposes insurer-mandated forced switching to biosimilars and is concerned over frequent nonmedical switching with biosimilars. In jurisdictions where substitution by someone other than the prescribing provider is lawful, the prescribing provider and the patient should be notified immediately when a substitution is made.”

The ACR recognizes that because biologics are so complex, they are expensive, and incite worry about the financial sustainability of the health care system and patients. They agree that biosimilars can help reduce the burden of cost if providers and patients can receive reassurance that they are safe and effective following rigorous scientific study of the products.

For more information on the 6 positions, 

Articles

The American College of Rheumatology (ACR) steadfastly supports the availability of safe and effective treatments for patients at the lowest cost possible, and underscores the necessity of scientific rigor for biosimilar use and approval.


ACR Supports Affordable Treatments, Use of Biosimilars Following Rigorous Approval Process

Patients with rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) have comparable positive attitudes towards biologics, and both felt that their specialists’ recommendations about biologic and targeted synthetic disease modifying agents (b/tsDMARDs) were trustworthy, even though most people also used other information sources, found an Australian study

The researchers sought to analyze patient beliefs about biologic and biosimilar therapy and what factors affect those beliefs. This is important because attitudes towards biosimilars can affect treatment adherence as well as impact a nocebo effect following a switch from a biologic originator.

In addition, while perceptions of patient and provider beliefs towards biosimilars has been explored, research contrasting populations with RA, or inflammatory arthritis (IA), as it is known in Australia and other parts of the world, and IBD, who see different specialists but use comparable biologics, has not yet been done.

“The introduction of biosimilars to the Australian pharmaceutical market has reduced the cost of biologics which may lead to easier access to these medicines with fewer restrictions in future. However, uncertainty regarding the concept of biosimilars and their regulatory process has created controversy around the prospect of switching from originators to biosimilars,” said the researchers.

Despite this, biosimilar use in rheumatology practice is increasing in Australia, although patient attitudes towards b/tsDMARD are not well understood. Australia currently has 3 etanercept biosimilars, 2 infliximab biosimilars, 8 adalimumab biosimilars, and 3 rituximab biosimilars.

An online questionnaire was advertised for people with a self-reported diagnosis of IA or IBD and combined the Belief about Medicines Questionnaire (BMQ) and the single-item literacy screener (SILS).

After exclusions, answers from 838 individuals were included in the final analysis (686 with IA, 144 with IBD, and 8 with both). Of those, 658 (79%) used b/tsDMARDs. The BMQ showed high necessity belief (median 4.2) with moderate concerns (median 2.8) about biologics.

The survey asked respondents not only where they got their medical information but also to note how favorable, or positive, they rated different information sources.

Most respondents (95%) got medication information from specialists, yet most used more than 1 source (median 4).

Specialists and specialist nurses were seen as the most positive source or information. A little over half (52%; 73/141) of respondents with IBD received information from specialist nurses compared with 202/685 (29%) with IA (

Those who responded with limited reading ability on SILS were more likely to discuss information with a general practitioner or pharmacist. Respondents who had higher BMQ scores and were younger were more likely to consult less reliable sources, such as social media.

More than half of respondents (60%) answered the biosimilar questions and just 23 (4.6%) said they were currently using a biosimilar and 336 (66.9%) weren’t sure if biosimilars were available in Australia.

Recommendation by a specialist was the most frequent factor that would prompt a patient to change from an originator to a biosimilar (71/1%; 352/495).

Respondents with IBD reported that specialist nurse information is valuable, but said specialist nurses for IA are not nearly as accessible or available, showing the need for more training and implementation of rheumatology specialist nurses.

Of note, the researchers said, “The very low proportion of respondents in this survey who were currently using biosimilars is surprising and calls into question whether patients are aware of being on biosimilars or bio-originators and if they are being appropriately informed about switching, as we were not able to confirm the actual medication the patients were using.”

Previously, patients taking originator products thought that treatment cost shouldn’t influence prescribing, which might explain why this study’s respondents, almost all of whom said they were on originator products, were unsure about and put low importance on biosimilar financial benefits.

Those who were more concerned about biologics were more likely to seek information on social media, but the directionality of that relationship has not been determined, the authors said.

Some key limitations in the study included that the results were skewed towards the IA group because sample sizes between groups were inequal, and there was an inherent selection bias in the English survey circulated by consumer groups that might not show real-life clinic patient populations. Also, the survey relied on self-reported diagnoses and data was collected in 2020, and biosimilar and biologic awareness might have grown since then, with more positive attitudes and physician and patient acceptance.

Khoo T, Sidhu N, Marine F, et al. Perceptions towards biologic and biosimilar therapy of patients with rheumatic and gastroenterological conditions. 

. Published online December 23, 2022. doi:10.1186/s41927-022-00309-4

Patients with rheumatoid arthritis (RA) and inflammatory bowel disease (IBD) have similar positive attitudes towards biologics and both trust their specialists’ recommendations, according to a recent survey conducted in Australia.

Patients With RA, IBD Trust Specialists’ Biologic and Biosimilar Recommendations

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 February 20th, 2023.

Number 5: Alex Jung and Kim Dwyer, both members of the Midwest Business Group on Health (MBGH) board of directors, discussed why employers should be ready for the 

 entering the market, and how they can prepare.

 of its pegfilgrastim biosimilar Stimufend (pegfilgrastim-fpgk), making it the fifth biosimilar referencing Neulasta to enter the market.

Number 3: In theory, by offering a lower-cost treatment option, biosimilars would help drive access for countless patients who simply could not afford the brand-name biologic. However, biosimilars have also 

 of the US health care system and its market forces.

Number 2: At the annual meeting of the Association for Accessible Medicines (Access 2023), 

 explained his dedication to and the inner workings of his online pharmacy that provides generic drugs to patients for significantly lower prices than traditional pharmacies.

Number 1: Biocon Biologics and its partner Viatris 

received a complete response letter (CRL)

 for their biosimilar referencing Avastin (bevacizumab), the second CRL for the companies in 2023. The news comes as Biocon publishes increased revenues for biosimilars and generics.

To read all of these articles and more, visit 

Videos

Here are the top 5 biosimilar articles for the week of February 20, 2023.

The Top 5 Biosimilar Articles for the Week of February 20

The incoming flood of biosimilars will require special preparation, emphasized Alex Jung and Kim Dwyer during a webinar from the Midwest Business Group on Health (MBGH) called “Employers and Biosimilars: Stories from the Real World.”

The Biosimilars Act (BPCIA) of 2009 predicted a savings of $37 billion in the United States, and because of the patent cliff and impending entry of more biosimilars into the market in the next 5 years, this number is expected to quintuple.

Jung, of Alex Jung Consulting, former principal of EY-Parthenon, and Dwyer, vice president of Inspera Health, gave an overview about biosimilars and provided examples about how this growth will affect employers. MBGH, where both serve on the board of directors, collected data from employer and workgroup interviews, and held an employer panel last year.

Dwyer illustrated how employers can be ready for the entry of biosimilars across 3 examples.

In the first employer story, the employer was wondering if biosimilars are always cheaper. This is not necessarily the case, Dwyer said, because a pharmacy rebate might be the most cost effective. With 7700 employees, he felt he didn’t have the leverage to negotiate his contract with his pharmacy benefit manager (PBM), so MGBH helped him look for other ways to save money, like with manufacturer coupons for biologics. When this approach steered him away from looking at biosimilars, he decided to hire a new independent pharmacy consultant to redo his PBM contract. 

For this first example, Dwyer emphasized that having an independent pharmacy consulting firm who is agnostic to the PBM can help employers identify what they want from a PBM contract.

Employers are facing a growing market for customized biological therapies, now currently estimated at $200 billion. However, Jung noted that a lot of branded products will lose patent protection in the patent cliff as biological drugs become biosimilars.

The second employer had no knowledge of biosimilars, Dwyer said, and wanted to learn more about what they were supposed to be asking about. MBGH provided this employer with J and Q codes and provided her with a list of questions she should be asking.

MBGH suggested she gather 3 years of data so that it could be measured. Both sets of data were extremely raw, almost intended to be a mystery, Dwyer said. From this, Dwyer emphasized to hold medical carriers and the PBM accountable for solid data reporting.

Dwyer also stressed the use of benchmarks to determine when biosimilar use is appropriate because it is not always necessarily true that the biosimilar will be more cost effective. Ideally, a biosimilar is both cost effective and clinically appropriate for the patient.

Finally, the goal of employer number 3, with 144,000 employees, was to see the outcome benefits from therapeutic switching. He had the resources to do his own research and compared his results against other employers’ findings, and his results were in the 90th percentile of achievement regarding compliance with therapeutic switching.

Ultimately, this employer learned that the biologic drug was sometimes intentionally being used over the biosimilar because it was cheaper than the biosimilar.
Testing drug efficacy for each patient is also important to make sure payment is being made for a drug that will be effective.

“Each and every time a new biosimilar emerges, have a conversation. And it’s not so much about the biosimilar emerging, it’s about what’s coming off patent,” said Dwyer.

Alex Jung and Kim Dwyer, both members of the Midwest Business Group on Health (MBGH) board of directors, discuss why employers should be ready for the explosion of biosimilars entering the market, and how they can prepare.



How Can Employers Be Ready for the Biosimilar Influx?

Here are the top 5 biosimilar articles for the week of February 13th, 2023.

Number 5: Amgen’s Amjevita (adalimumab-atto) has 

 the US market, making it the first of potentially 10 biosimilars referencing Humira to launch in 2023.

Number 4: IQVIA’s Biosimilars in the United States 2023-2027 report found that while the US biologics market has grown 12.5% annually over the last 5 years, 

 and is expected to reach $129 billion by 2027.

 the company’s biologics license application (BLA) for its denosumab biosimilar candidate for review.

 on its Eylea (aflibercept) biosimilar; Sandoz received a thumbs up from the European Union’s Committee for Medicinal Products for Human Use (CHMP); and Shanghai Henlius Biotech began a phase 1 study for its daratumumab biosimilar candidate.

Number 1: Sonia T. Oskouei, PharmD, vice president of biosimilars and specialty at Sandoz, foreshadowed how the 

US market introduction of adalimumab biosimilars

 could influence future biosimilar entrances and discussed why educational efforts need to be tailored to different specialties and stakeholders.

Here are the top 5 biosimilar articles for the week of February 13, 2023.

The Top 5 Biosimilar Articles for the Week of February 13

 study for SB4 in South Korea, the first approved biosimilar of etanercept, a biologic tumor necrosis factor (TNF) inhibitor that treats various autoimmune diseases, showed comparable effectiveness and safety to previous SB4 real-world evidence.

The reference biologic TNF inhibitor etanercept treats such autoimmune diseases as axial spondylarthritis (axSpA), rheumatoid arthritis (RA), psoriatic arthritis (PsA), and plaque psoriasis (PsO). Previously, SB4, from Samsung Bioepis, had proved 

In the current study, the researchers were trying to evaluate end points of safety (primary end point) and effectiveness (secondary end point) of SB4 in routine clinical practice, as is customary in the Korean drug approval process. 

In the United States, there are 2 approved etanercept biosimilars, and 3 etanercept 

 have been approved in the European Union.

Patients in the prospective, multicenter, open-level, observational study included both those who were etanercept-naïve or those who were switched from reference etanercept; patients had axSpA, RA, PsA, and PsO. The study ran from September 2015 to September 2019. In the safety analysis, 176 patients had axSpA and 138 had RA.

Patients were administered SB4 weekly via subcutaneous injections with a prefilled syringe. Safety was evaluated by the incidence of adverse events (AEs), adverse drug reactions (ADRs), and serious adverse events (SAEs). Effectiveness was evaluated by the change from baseline of investigator-rated Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) in patients with ankylosing spondylitis (AS) and disease activity score-28 (DAS28) in patients with RA.

Following injection, AEs were seen in 17.8% of patients, ADRs in 9.9%, and serious AEs in 1.3%. Most AEs were mild or moderate (66.7% and 31.1%, respectively) and unrelated to SB4 (58.9%).

The most frequent AEs were injection-site pruritus (1.9%) and injection-site rash (1.3%). At week 24, mean disease activity scores were significantly lower compared with baseline in etanercept-naïve patients with AS and RA (BASDAI, 2.7 vs 6.2; 

< .0001) and in switched patients with AS and RA (BASDAI, 1.0 vs 1.3; 

The general incidence rates of AEs and SAEs in this study were lower than those seen in 299 RA patients in the 

 of SB4 (55.2 and 4.3%, respectively). The researchers of the present study think this may be because of different baseline patient characteristics since this study included naïve and switched patients, while the phase 3 study only included naïve patients. Only patients with RA had arthralgia, synovitis, and tenosynovitis SAEs because of their underlying disease. Nausea, pneumonia, and dizziness SAE’s were determined as drug-related. 

The study had a high retention rate, similar to a previous study. The researchers noted that routine monitoring of patients on biosimilars can help address disease flares and provide an opportunity to educate patients to resolve possible negative perceptions of biosimilars, thereby increasing acceptance of these products and reducing discontinuation.

A limitation of the study is the small number of subjects (naïve or switched patients per indication) and that only patients with axSpA and RA were enrolled. In addition, how long patients received reference etanercept and a record of when they switched to SB4 was not recorded, so the impact of this is unknown. Additionally, efficacy-related outcomes were not recorded in complete detail. Biases may have been introduced by the noncomparative open label design, the shortness of the study (24 weeks), and quantity of patients.

Yoo WH, Kang YM, Kim DW, et al. Safety and effectiveness of etanercept biosimilar SB4 for rheumatic diseases in South Korea: real-world post-marketing surveillance data. 

. Published online December 8, 2022. doi:10.1007/s40744-022-00515-z

The first phase 4 postmarketing surveillance study for SB4 in South Korea as the first approved biosimilar of etanercept demonstrated comparable effectiveness and safety to previous SB4 evidence. 

Phase 4 Study Finds Comparable Safety, Efficacy Between Etanercept Biosimilar, Enbrel for Autoimmune Diseases

Here are the top 5 biosimilar articles for the week of January 30th, 2023.

Number 4: Sarfaraz K. Niazi, PhD, explained the 

 to the drug review process, the significance of each change, and the published pieces of work that helped inform the FDA's decisions.

 as part of the Biosimilars User Fee Act III regulatory research pilot program. The roadmap will allow stakeholders to see how the program will help the FDA enhance regulatory decision-making surrounding biosimilar development.

Number 2: This year started off with a bang for 

, with several regulatory approvals around the world, new market insight into the global use of biosimilars, and US market introduction of the first rival biosimilar to Humira (adalimumab).

Number 1: Amgen’s Amjevita (adalimumab-atto) has 

Here are the top 5 biosimilar articles for the week of February 6, 2023.

The Top 5 Biosimilar Articles for the Week of February 6

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.

 has revealed that if the Inflation Reduction Act (IRA) had been implemented in 2020, Medicare Part D beneficiaries could have saved a total of $734 million, averaging out to about $500 per member.

Number 4: As part of a series of interviews, Kyung-Ah Kim, executive vice president of Samsung Bioepis, 

 into how developers view the current biosimilars market, the relevance of interchangeability, and the usefulness of clinical efficacy testing.

Number 3: Sarfaraz K. Niazi, PhD, explained the 

Number 2: Saudi Arabia approved an adalimumab biosimilar, a denosumab biosimilar entered the market in the Republic of Korea, and Dr. Reddy’s Laboratories 

 of a phase 3 study for its rituximab biosimilar

Here are the top 5 biosimilar articles for the week of January 30, 2023.

The Top 5 Biosimilar Articles for the Week of January 30

Researchers in China found that a denosumab biosimilar (LY06006) increased lumbar spine bone mineral density (BMD) and decreased bone resorption in postmenopausal women with a high risk of fracture, indicating that LY06006 might be an effective osteoporosis treatment.

, attempted to determine the efficacy, safety, pharmacokinetics, and immunogenicity profiles of the denosumab biosimilar (LY06006) in Chinese postmenopausal women with osteoporosis and a high fracture risk.

A randomized, double-blind, placebo-controlled, multicenter phase 3 study was conducted within various hospitals throughout China to examine the bioequivalence of LY06006 to reference denosumab (Prolia), an already available therapy for osteoporosis. Prolia is a fully human monoclonal antibody for nuclear factor-kappa B ligand (RANKL) and has been used to treat patients with osteoporosis for more than 10 years.

In the study, LY06006, a recombinant anti-RANKL whole human monoclonal antibody injection, displayed high similarity with reference denosumab when studied in the pharmaceutical and nonclinical spheres and showed clinical localization consistent with that of the reference. Researchers found LY06006 to be well tolerated with no unexpected adverse reactions.

Across 49 medical centers in China, 448 postmenopausal women aged 50 to 85 years with osteoporosis were randomly assigned (3:1) to receive 60 mg of LY06006 or placebo subcutaneously every 6 months for 1 year. Change in lumbar spine BMD was the primary end point. This study was performed from June 2019 to August 2021.

Of the 448 participants, 409 (LY06006, n = 311; placebo, n = 98) finished the study. All participants were involved in the intent-to-treat trial, 427 (95.3%) were in the full analysis set, 408 (91.1%) were in the per protocol set, 446 (99.6%) were in the safety set, and 336 (75.0%) were in the pharmacokinetics concentration set.

Study participants were also given daily 500 mg oral calcium and 600 IU vitamin D supplements during the study.

In terms of efficacy, a 4.71% (95% CI, 3.81%-5.60%) treatment difference in percent change in lumbar spine BMD from baseline to month 12 was seen in the LY06006 group compared with the placebo group (

< .0001). Rising lumbar spine BMD levels were associated with LY06006 at the 6-month mark.

The serum C-terminal telopeptide of type 1 collagen (CTX) change rate in the LY06006 group decreased by 78.42% (95% CI, 75.30%-81.64%), 58.66% (95% CI, 54.07%-63.41%), and 61.15% (95% CI, 54.97%-66.68%) compared with the placebo group at months 1, 6, and 12, respectively (all 

Serum procollagen type I N-terminal propeptide (PINP) change rates at the 1-, 6-, and 12-month marks in the LY06006 group compared with the placebo group were decreased by 15.69% (95% CI, 12.58%-18.71%), 53.89% (95% CI, 49.74%-58.15%), and 55.31% (95% CI, 50.33%-59.88%), respectively (all 

Adverse events were experienced by 264 (78.6%) LY06006 group participants and 83 (75.5%) placebo group participants. The most common treatment-emergent adverse events experienced by participants were urinary tract infections and upper respiratory tract infections.

The PubMed database contains only 1 other phase 3 clinical study on a denosumab biosimilar, which had a smaller sample size, suggesting that the results of this study might be more illustrative of the benefits of LY06006 across a larger sample size.

However, a limitation was that Prolia was not approved in China at the start of the study, so researchers were unable to directly compare LY06006 with Prolia.

A denosumab biosimilar such as LY06006 could help additional patients by increasing drug accessibility and lowering health care costs, the authors noted.

They concluded that ostmenopausal women with a high risk of fracture can be helped by a denosumab biosimilar such as LY06006, especially if biologics for the condition are high in cost or difficult to access.

Gu J, Zhang H, Xue Q, et al. Denosumab biosimilar (LY06006) in Chinese postmenopausal osteoporotic women: a randomized, double-blind, placebo-controlled, multicenter phase III study. 

. 2022;38:117-125. doi:10.1016/j.jot.2022.06.007

Researchers found that a denosumab biosimilar appeared comparably safe and effective to reference drug Prolia.

Study: Denosumab Biosimilar Looks Promising for Osteoporosis in Phase 3 Trial

Ryan Haumschild, PharmD, MS, MBA, director of pharmacy services at Emory Healthcare and Winship Cancer Institute, tackles how stakeholders can collaborate and utilize market data to effectively boost biosimilar uptake.

How can different stakeholders work together to ensure improved biosimilar utilization across disease states?

I think that’s one of the things that we want to continue to expand upon. How do we get good biosimilar use in oncology, but then good biosimilar use in the immunology disease states, such as rheumatology and gastroenterology? And believe it or not, there’s different uptakes between the different disease states. If we’re using biosimilars and we’re extrapolating data to treat patients in the curative intent, how can we not extrapolate data from gastroenterology to rheumatology, and then start to look at interchangeability?

There’s going to be a never-ending appetite for data, and that’s okay because we’re data driven. How can we leverage the experiences we’ve had and the similar outcomes between reference projects and biologics, and move that into the biosimilar space, so that we can make more timely approvals? Not just wait for every single study and every single patient. And also look at switching immunogenicity and feel comfortable moving forward biosimilars across the board.