Cameron Santoro is an associate editor for The Center for Biosimilars

Cameron Santoro

The Top 5 CFB Articles for the Week of January 1

top 5 most-read rheumatology stories of 2023

 included the changing market dynamics in the adalimumab space, including new launches and interchangeability labels, as well as the addition of Stelara and Enbrel to the list of originators up for Medicare price negotiation.

 include the US market launch of Fylnetra, the sixth pegfilgrastim biosimilar on the market, the FDA approval for an autoinjector pegfilgrastim biosimilar, and more.

top 5 most-read ophthalmology stories of 2023

 concerned clinical results, approvals, and launches for ranibizumab and aflibercept biosimilars.

top 5 most-read regulatory stories of 2023

 covered the FDA approvals for the first ustekinumab biosimilar and the first subcutaneous infliximab product, as well as other regulatory updates.

regulatory structure of biosimilar development

 can be safely streamlined and made more efficient and less costly, wrote authors from Sandoz, Fresenius Kabi, Boehringer Ingelheim, and Samsung Bioepis in an opinion article published in BioDrugs.

To read all of these articles and more, visit 

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

The Top 5 Biosimilar Articles for the Week of January 1

Doctor calculating costs | Image Credit: NINENII - stock.adobe.com

 from Europe demonstrated that switching from Humira (reference adalimumab) to SB5 biosimilar was effective and safe for adults with inflammatory diseases, further supporting that SB5 can serve as a lower-cost alternative to the originator.

Immune mediated inflammatory diseases (IMIDs) range from rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), Crohn disease (CD), and ulcerative colitis (UC). In August 2017, the European Medicines Agency approved SB5, also known as Imraldi, and it was accessible as prescribed in October 2018. Prior to the approval and launch, SB5 expressed equivalent efficacy with similar pharmacokinetic, safety, and immunogenicity to the reference adalimumab in phase 1 and 3 trials.

The study design of the non-interventional, single-cohort, real-world PROPER trial included specialists from Germany, Spain, Italy, the United Kingdom, Ireland, and Belgium. The cohort had a total of 955 participants with IMIDs who transitioned from the originator to SB5: 207 with RA, 127 with axSpA, 162 with PsA, 447 with CD, and 12 with UC. Participant clinical characteristics at baseline included sex, relevant medical history, age at SB5 initiation, disease duration, disease activity score and relevant concomitant therapy. Other characteristics were based on disease type, dose, regimen, and method of SB5 administration during the study. SAS version 9.4 or higher was used when conducting each statistical analysis.

Disease activity scores depended on the IMID associated with the participant. For patients with RA, calculations used Disease Activity Score in 28 joints using C-reactive protein and Funktionsfragebogen Hannover. Patients with axSpA utilized the bath ankylosing spondylitis disease activity index. Patients with PsA are measured with the Psoriatic Arthritis Response Criteria swollen joint count (of 66 joints) and tender joint count (of 68 joints). The Harvey-Bradshaw Index (HBI) can assist with determining severity in patients with CD while patients with UC use the Partial Mayo Score.

Out of the original 955, 932 completed follow-up and 722 received SB5 through week 48. Kaplin-Meier estimates of persistence on SB5 at week 48 were 0.86 (95% CI, 0.80-0.90) for RA, 0.80 (95% CI, 0.71-0.86) for axSpA, 0.81 (95% CI, 0.74-0.86) for PsA, and 0.72 (95% CI, 0.67-0.76) for the CD cohorts. Adverse reactions were the main reason participants discontinued SB5 (n = 79) due to reactions of the injection site (n

66). Out of the participants who reported on 48 week follow-up, 722 (75.6%) were still taking SB5, with the most common dose beginning at baseline of 40 mg every 2 weeks.

Of the patients with RA, 59.2% were in remission at baseline, whereas 57.2% achieved remission in week 48. Patients with axSpA had 81% in remission at baseline and 93.7% at week 48. The HBI score in patients with CD was 84% at baseline and 85.1% at week 48. Remission was determined in 58.4% of patients with UC at baseline and in 83.3% at week 48. In the RA, axSpA, and CD cohorts, SB5 discontinuation had hazard ratios more prevalent in female participants prior to the 48 weeks (3.53, 2.38, 2.21, respectively). The slight changes from baseline initiation of SB5 among the variety of disease cohorts’ overtime did not represent any major differences.

After transitioning, mild adverse drug reactions (ADRs) and serious adverse events (SAEs) were evaluated in the study duration. In total, 232 patients experienced at least 1 mild ADR. However, none of the SAEs were fatal. Disease flares were also considered, and dose adjustments were required for patients enduring flare.

Study limitations were present in the data collection. The population disparities may have altered the findings due to the heterogeneity in healthcare systems. Regional and site effects failed to be accounted for in the analysis. The small proportion of candidate predictors did not allow consideration of all potential information.

The real-world use of SB5 as treatment for patients with IMIDs proved efficacy and tolerance when transitioning from the originator. However, the authors noted, “particular consideration should perhaps be given to female patients who are considering switching, since they appear to be more susceptible to discontinuation than their male counterparts”.

Müller-Ladner U, Dignass A, Gaffney K, et al. The PROPER study: A 48-week, pan-European, real-world study of biosimilar SB5 following transition from reference adalimumab in patients with immune-mediated inflammatory disease. 

 2023;37(6):873-889. doi:10.1007/s40259-023-00616-3

Articles

Adults with inflammatory diseases maintained disease control when transitioning from originator adalimumab (Humira) to biosimilar SB5 in a pan-European study. 

Biosimilar SB5 Matches Originator in Safety, Efficacy for Inflammatory Diseases After Switching

The Top 5 Biosimilar Articles of 2023

 on the market: Fresenius Kabi's Idacio (adalimumab-aacf) and Biocon Biologic's Hulio (adalimumab-fkjp). The launches come after 5 launched over the Fourth of July weekend.

Number 4: After years of waiting and legal battles, the first of the 

8 adalimumab biosimilars expected to launch in July 2023

 have entered the market: Boehringer Ingelheim’s Cyltezo (adalimumab-adbm), Coherus Biosciences’ Yusimry (adalimumab-aqvh), Organon and Samsung Bioepis' Hadlima (adalimumab-bwwd), and Sandoz' Hyrimoz (adalimumab-adaz).

 (J&J) over the former’s ustekinumab biosimilar referencing Stelara, delaying the projected launch of the candidate from late 2023 to January 2025.

Number 2: In a real-world study in India, patients with ankylosing spondylitis (AS) who were treated with the 

 for 10 weeks showed improvements in disease activity that persisted through 48 weeks.

updated look on the adalimumab biosimilars

 that are coming down the US pipeline as well as what stakeholders need to know and how they can prepare ahead of the US launch of 8 adalimumab biosimilars in July 2023.

Here are the top 5 biosimilar articles for 2023.

The Top 5 Biosimilar Articles for the Week of December 18, 2023

Number 5: After Humira’s patent expired in 2018 in the European Union (EU) and earlier this year in the US, 10 adalimumab biosimilars entered the market in the EU and 

 discussed the characteristics of the available biosimilars to help clinicians navigate the various options with their patients.

Number 4: Two Taiwanese posters from the 

San Antonio Breast Cancer Symposium (SABCS)

 2023 annual meeting evaluated the real-world implications of using trastuzumab biosimilars, particularly Ogivri (trastuzumab-dkst) in patients with HER2-postive breast cancer.

Number 3: Among patients with rheumatoid arthritis (RA) registered with the British Society for Rheumatology Biologics Register in Rheumatoid Arthritis (BSRBR-RA), those treated with 

 showed similar treatment responses and drug survival rates vs those treated with etanercept originator. The findings were published in 

 that can help patients, caregivers, and providers navigate decision-making and treatment conversations for multiple disease states.

FDA agreed to review an application for Hadlima

 (adalimumab biosimilar) to be granted interchangeability; The European Union’s Committee for Medicinal Products for Human Use (CHMP) gave a positive opinion for an ustekinumab biosimilar; the Biosimilars Forum expressed support for Senate Finance Committee’s draft legislation promoting biosimilars.

Here are the top 5 biosimilar articles for the week of December 18th, 2023. 

The Top 5 Biosimilar Articles for the Week of December 18

Illustration of doctors researching | Image Credit: VIX - stock.adobe.com

 on originator adalimumab (Humira), in comparison to the biosimilar, adalimumab-aqvh, showing comparable safety and efficacy between the products in their study, which was published in 

 by the FDA under the brand name, Yusimry, to treat rheumatoid arthritis, hidradenitis suppurativa, Crohn disease, ulcerative colitis, juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis, and ankylosing spondylitis. Since the approval of the biosimilar, assessments on the physiochemical and functional attributes between the originator and adalimumab-aqvh have included quality factors based on mechanism of action.

Various materials and methods were applied for the comparative analytical assessment, based on risk ranking of the product quality attributes. The results were either similar criteria between the originator and adalimumab-aqvh or they were identical. Both adalimumab and adalimumab-aqvh had visible stability with functional activities.

Of the assorted methods, the majority of all principles were met to standard. The primary structure exhibited parallel peptides with the same masses, confirming 100% coverage. The higher order structure’s fluorescence profiles and emission maxima were also comparable between adalimumab and adalimumab-aqvh. Glycosylation in both medications were identical in most glycan categories, aside from terminal galactose and sialic acid. The high-molecular-weight species were proportionate outcomes among both drugs, meeting acceptance criteria yet again.

Slight differences were amid the originator adalimumab and the biosimilar. For starters, adalimumab-aqvh size variants were either similar or expressed a lower-molecular-weight species, resulting in greater monomer in relative areas. Charge variants, measured by cation-exchange chromatography, differed in acidity with only 1 adalimumab-aqvh lot above the range of the originator. The hydrophobic variables included oxidized fragment crystallizable (fc) variants within the average data, excluding one lot. Post-translational modifications had similar outcomes in all 5 levels monitored by adalimumab and adalimumab-aqvh. Free thiol and host-cell proteins had lower numbers in adalimumab-aqvh when compared to the originator drug but both categories achieved accepted criterion.

Overall, adalimumab-aqvh received identical numbers of or slightly fewer non-spherical particles than originator adalimumab. In areas surrounding fragment antigen-binding (fab) associated biological activity, the association constant and disassociation rate constant had similarities between both medications. The binding of membrane tumor necrosis factor-α with adalimumab and adalimumab-aqvh had similar results. An assay based on fab- and fc-associated biological activity had accepted variability, despite the biosimilar above the range of antibody dependent cell cytotoxicity. Partial disparities in biosimilars did not affect CDC activity in comparison to the originator lots. Binding affinity was similar in both medications with a fairly lower binding affinity outside of the 3 standard deviation range of the originator.

The stable data selected through assays encourages the biosimilarity support of similar functions between adalimumab and adalimumab-aqvh. Despite brief differences, similarity criteria were met for most of the glycan categories, amino acid sequences, and disulfide structures. There was no significant impact on the potency or efficacy in the minor physicochemical differences. The authors concluded, “The similarities between adalimumab-aqvh and adalimumab predict similar efficacy and safety outcomes in clinical trials, which was confirmed by the pharmacokinetic, safety, immunogenicity, and efficacy clinical trials that have been conducted.”

Jiang Y, Arora T, Klakamp S, et al. Demonstration of physicochemical and functional similarity of biosimilar adalimumab-aqvh to adalimumab. 

. 2023;23(4):377-395. doi:10.1007/s40268-023-00437-3

Comprehensive assay research concluded similar structures, functions, and stability between reference adalimumab (Humira) and adalimumab-aqvh.

Assays Reveal Equivalence Between Adalimumab-aqvh and Humira

The Top 5 Biosimilar Articles for the Week of December 11

Number 5: Brian Biehn, senior director of biosimilar commercialization at Cencora, formerly known as AmerisourceBergen, recaps some of 

the major regulatory updates for biosimilars

 in the United States and makes predictions for how the market will develop in the years to come.

Number 4: After Humira’s patent expired in 2018 in the European Union (EU) and earlier this year in the US, 10 adalimumab 

 in the EU and 8 entered the market in the US. A 

 discussed the characteristics of the available biosimilars to help clinicians navigate the various options with their patients.

 and safety of GP2017 in patients with inflammatory bowel disease (IBD) who were naïve to adalimumab or switched from the originator (Humira) or another adalimumab biosimilar.

estimated the impact of biosimilar substitution

 on total cost of care (TCOC) and provider financial performance in the final performance period of the Oncology Care Model.

Number 1: A report from IQVIA noted that Europe could miss out on €15 billion in cost savings by not having 

 about to lose market exclusivity, shedding light on the implications for overall health care savings and ultimately, patient access.

Here are the top 5 biosimilar articles for the week of December 11, 2023.

Image Name | Image Credit: tashatuvango - stock.adobe.com

Among patients with rheumatoid arthritis (RA) registered with the British Society for Rheumatology Biologics Register in Rheumatoid Arthritis (BSRBR-RA), those treated with etanercept biosimilar showed similar treatment responses and drug survival rates vs those treated with etanercept originator. The findings were published in 

In the early 2000s, etanercept was one of the first biologic therapies licensed as a treatment method for patients with RA. The observational BSRBR-RA study monitors the long-term safety of biologics in routine practice, and for the current study, patients enrolled from 2010 were included. The authors aimed to compare outcomes of the originator vs the biosimilar after 6 and 12 months of therapy.

Patient characteristics included age, gender, disease duration, disease activity using core outcome variables, patient global visual analogue scale, erythrocyte sedimentation rate (ESR) and/or C-reactive protein (CRP) and the 28-joint DAS, functional ability using the health assessment questionnaire (HAQ), and the current or previous anti-rheumatic therapies they received. The observational prospective cohort study operated from January 1, 2010, to June 16, 2022, where every patient had at least 1 year of follow-up.

The core outcome variables of disease activity, DAS28, and HAQ were reviewed at baseline, 6 months, and 1 year. Statistics were calculated using the proportion of patients who achieved DAS28 remission (DAS28 < 2.6), European Alliance of Associations for Rheumatology (EULAR) response (good: 6-month DAS28 ≤ 3.2 and improvement > 1.2 units; no response: 6-month DAS28 ≤ 5.1 and > 3.2 with improvement ≤ 0.6 units; moderate all others), and minimal clinically important difference (MCID) in HAQ (reduction in HAQ score ≥.22 units). Primary outcome statistics were DAS28 remission, any EULAR response (moderate and good vs no response), good EULAR response (vs moderate/no response) and MCID in HAQ. Ethnicity, joint surgery history, anti-CCP positivity, rheumatoid factor (RF) positivity, smoking status, disease duration, and body mass index were among additional variables included to offset any missing data.

Drug survival was calculated using the Kaplan-Meier method amongst cohorts, adjusted by propensity deciles. The study utilized the Cox proportional hazards model to compute the regression of patients on etanercept originator who halted therapy after time in comparison to patients on the biosimilar, modified by propensity deciles. Analyses were determined using Stata version 14, a multilevel survey model.

Results demonstrated similar disease activity between the cohorts starting etanercept as their first biologic of the originator vs the biosimilar. Each cohort had a median improvement of DAS28 from baseline to 6 months, with a median improvement of 2.4 units at 6 months and a median of 2.5 units at 1 year. Patients with RA reached DAS28 remission at 6 months of therapy in 26% of the originator group and 31% of the biosimilar participants. The classification of a good EULAR response was met by 38% of the originator cohort after 6 months while the biosimilar group achieved 45%. After 6 months, 41% of the originator cohort attained MCID in HAQ while the biosimilar cohort was at 47% (95% CI, 0.57-0.97). Both the etanercept originator and biosimilar cohorts had 35% of patients achieve MCID in HAQ from baseline to 1 year. The Cox proportional hazards model proved etanercept originator group versus the biosimilar group were no more likely to stop therapy than the other one (95% CI, 0.99-1.33).

Study limitations were mainly the large gap of time between the approval of the originator drug to the earlier approval of the 2016 biosimilar. This could likely lead to bias since the biosimilar patients had less follow-up in comparison to the originator participants. The study focused on patients from 2010 and beyond because patients with RA may be vastly different to those of more recent.

The national cohort study proved the etanercept originator had closely similar treatment effects on the patients beginning the biosimilar regarding disease activity and drug survival. Neither group was more likely to halt etanercept therapy after 1 year with 71% on the originator and 76% on the biosimilar. The authors conclude, “These data are reassuring to both patients and clinical teams when considering starting etanercept originator or biosimilar therapy as their first biologic”.

Kearsley-Fleet L, Rokad A, Tsoi MF, et al. Etanercept originator versus etanercept biosimilar for the treatment of rheumatoid arthritis as a first biologic: results from the BSRBR-RA. 

. 2023;62(12):3849-3857. doi:10.1093/rheumatology/kead127

A national study on patients with rheumatoid arthritis (RA) compares the disease activity and drug survival rate between an etanercept biosimilar and the originator (Enbrel).

Study Shows Similar Efficacy, Drug Survival Rates for Etanercept Biosimilar vs Originator in RA

Here are the top 5 biosimilar articles for the week of December 4, 2023. 

The Top 5 Biosimilar Articles for the week of December 4, 2023

 noted that Europe could miss out on €15 billion in cost savings by not having biosimilars for medications about to lose market exclusivity, shedding light on the implications for overall health care savings and ultimately, patient access.

 where data were collected from patients with inflammatory bowel disease (IBD) showed safety and efficacy of the adalimumab biosimilar HS016.

Number 3: Several companies make moves to further their 

, Regeneron sues Celltrion over biosimilar for Eylea (aflibercept), and Health Canada grants marketing authorization for biosimilar referencing Stelara (ustekinumab). 

Number 2: Sarfaraz K. Niazi, PhD, offers hope for the end of 

 in the United States in his latest column.

Number 1: With numerous adalimumab biosimilars launched in the United States in 2023, the impact of an 

 has been extensively discussed with much speculation, but its commercial significance is yet to be determined.

The Top 5 Biosimilar Articles for the Week of December 4

A study confirmed the effectiveness and safety of GP2017in patients with inflammatory bowel disease (IBD) who were naïve to adalimumab or switched from the originator (Humira) or another adalimumab biosimilar.

The observational, multi-centric, retrospective 

 was conducted in 2 IBD centers in Northern Italy by analyzing patients with IBD, an umbrella term for Crohn disease (CD) and ulcerative colitis (UC). Data surrounding GP2017 has been scarce, especially in patients with IBD, since its July 2018 European Medicines Agency (EMA) approval was supported by data testing the product in plaque psoriasis. GP2017 (Hyrimoz/Hefiya) 1 of 10 EMA-approved adalimumab biosimilar.

Participants included patients with a diagnosis of CD or UC, ongoing or previous therapy for GP2017, and at least 6 months of follow up after beginning the GP2017. The patients were administered subcutaneous injections of 160 mg at baseline, 80 mg at 2 weeks, followed by 40 mg maintenance doses every 2 weeks for patients naïve to adalimumab. However, patients who switched from the originator or from another biosimilar received a standard maintenance dose of 40 mg every 2 weeks.

Overall, the study included a total of 72 patients with an IBD diagnosis. GP2017 was administered to 29 patients (40.3%) as the first form of adalimumab therapy. There were 33 patients that were first treated with the adalimumab originator (45.8%) and 10 who were initially treated with a different adalimumab biosimilar (13.8%).

Prior to GP2017 treatment, 5 patients reported clinical remission (17.2%), 16 had mild disease activity (55.1%), and 8 communicated moderate-to-severe activity (27.6%). After 6 months, 10 of the 29 treated with GP2017 were considered in remission (34.5%), 17 had mild activity (58.6%), and 8 had moderate-to-severe activity (27.6%). Following 12 months, 17 patients concluded remission (58.6%), 9 reported mild activity (31%), and only 1 patient had moderate-to-severe activity present (3.5%). There were 5 patients in remission at baseline, 10 patients after 6 months (P = .0005) and 17 patients noted remission after 12 months (P = .001).

Overall, 33 patients were switched from the originator to GP2017. When first administered, 25 patients reported clinical remission (75.8%), 6 were in mild activity (18.2%), and 2 had moderate-to-severe activity present (6%). The following 6 months included 26 patients reaching remission (78.8%), 4 with mild activity (12.1%), and only 1 out of 33 had moderate-to-severe activity (3%). After the 12-month follow-up period ,26 patients were in clinical remission (78.8%), 2 had mild activity (6.1%), and 0 patients had moderate-to-severe activity. 

Regarding the 10 participants who switched from another adalimumab biosimilar to GP2017, at baseline, 6 patients were in clinical remission, 3 had mild activity present, and only 1 had moderate-to-severe activity. At 6-months ,7 patients were in remission, 2 had mild activity, and 1 patient had moderate-to-severe activity. At month 12, 7 patients were in remission, 2 had mild activity, and 0 patients had moderate-to-severe activity.

Only 11 patients experienced nonserious side effects, including headache, allergic reactions, arthralgia, and cutaneous manifestations, in line with those identified for the originator. Additionally, 9 patients discontinued treatment, mainly due to adverse events or secondary failure.Study limitations surrounded the observational data collection potentially influenced by missing information or demographics, absence of certain procedures, lack of control groups, and smaller sample sizes for UC compared to patients with CD. Statistics could be affected regarding the subgroup sample size of patients who switched from other adalimumab biosimilars.

The author stated, “Moreover, the retention rate and safety profile are comparable to those present in the literature regarding the originator, justifying the feasibility to switch from the originator to a biosimilar or from biosimilar to biosimilar.”

Vernero M, Bezzio C, Ribaldone DG, et al. Efficacy and safety of adalimumab biosimilar GP2017 in patients with inflammatory bowel disease. J. ClinMed. 2023; 12(21):6839. doi:0.3390/jcm12216839

Patients with inflammatory bowel disease (IBD) receive additional evidence on the safety and efficacy of adalimumab biosimilar GP2017 treatment.  

Adalimumab Biosimilar GP2017 Shows Similar Safety, Efficacy to Originator in Patients With IBD 

Here are the top 5 biosimilar articles for the week of November 27, 2023. 

The Top 5 Biosimilar Articles for the Week of November 27

Number 5: Although biosimilars have already generated savings for Medicare Part B programs and beneficiaries, opportunities for 

 in spending remain, according to a report from the HHS.

 their adalimumab biosimilars, Regeneron sues Celltrion over biosimilar for Eylea (aflibercept), and Health Canada grants marketing authorization for biosimilar referencing Stelara (ustekinumab).

Number 3: Biosimilar experts highlight the persisting confusion around 

 for biosimilars, including misunderstandings about the definition of interchangeability and the purpose these labels serve.

Number 2: As new biosimilars are added to CVS Caremark’s standard formulary, 

. One notable change is with the Humira biosimilars: the pharmacy benefit manager has removed Amjevita in favor of Hyrimoz and an unbranded biosimilar.

Number 1: Sarfaraz K. Niazi, PhD, offers hope for the end of interchangeability labels in the United States in his 