Cameron Santoro is an associate editor for The Center for Biosimilars

Cameron Santoro

The Top 5 Biosimilar Articles for the Week of January 15

Number 5: Sarafraz K. Niazi, PhD, previews the new year and his hopes for the 

 for biosimilar approvals using examples from history of other scientific concepts that took time to gain traction.

 has announced that it will remove AbbVie’s blockbuster immunosuppressive drug Humira from some of its preferred formulary drug lists in favor of more affordable biosimilar options for the drug. Starting April 1, 2024, Hyrimoz and an unbranded version of Humira manufactured by Sandoz will be covered across all CVS formularies, with branded and unbranded near copies of Humira manufactured by Biocon covered on some reimbursement lists.

Number 3: IQVIA’s report on the impact 

 has had on Europe’s health care space identified ongoing challenges with biosimilar access and generating savings, calling for more policies focusing on fostering a sustainable market for years to come.

Number 2: As Regeneron gears up for a legal battle with 

 for its reference aflibercept, CareFirst files a lawsuit against Johnson & Johnson (J&J) for restricting biosimilar ustekinumab competition, and Celltrion and Accord BioPharma file with the FDA to approve their respective biosimilar candidates.

 (EMA) granted marketing authorization to Uzpurvo, the first biosimilar to reference Stelara (ustekinumab). The biosimilar is indicated for Crohn disease, psoriatic arthritis, and plaque psoriasis.

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 15, 2024. 

Blood test | Image Credit: luchschenF - stock.adobe.com

Two rituximab biosimilars (Rixathon and Truxima) and the reference drug (Rituxan) exhibited similar safety and efficacy outcomes in patients with immune thrombocytopenia (ITP), an autoimmune disease followed by a low platelet count, according to a recent analysis.

Between January 2018 and December 2019, an 

observational, multicenter, retrospective and prospective study

 was conducted among several medical centers in France. Study participants included adults with ITP who were administered at least 1 rituximab biosimilar infusion.

The main study objective was to evaluate the safety and efficacy of rituximab biosimilars in comparison with the reference product. Diagnosis was determined by international guidelines to determine the bleeding severity of the patients, graded from 1 to 19, where anything greater than 8 was labeled severe. The study examined data from 10 centers. The authors also noted that the real-life study scenario is comforting to patients and doctors who use or suggest this off-label drug when relying on accurate data research.

Outcomes were divided into complete response (CR), with a platelet count greater than 100 × 10

/L and partial response (PR), with a platelet count of 30 to 100 × 10

/L with at least a doubling of the pretreatment count. The final or overall response (OR) was either labeled as CR or PR. Patients labeled as non-responders required another treatment, including a new rituximab routine, despite the platelet count.

Treatment efficacy was calculated using the initial response rates between rituximab-naïve biosimilar patients and matched controls. The 3-month post-transfusion response was the main outcome determining efficacy. A total of 49 patients with ITP were administered Rixathon and 49 patients with ITP were treated with Truxima. There were 38 patients in the Rixathon group and 43 patients in the Truxima group. Patients had paracetamol, corticosteroids, and antihistaminic treatments administered as pre-infusion.

OR was achieved in 27/38 (71%) patients in the Rixathon group and 22/42 (51.2%) patients in the Truxima cohort. Following the first infusion, the median platelet count for the Rixathon cohort was 89 × 10

/L (range, 53.5-156.5) after the first 3 months. For the Truxima group, 82 × 10

/L (range, 50.3-197) was the median platelet count after 3 months. Ten patients experienced relapse after an average of 7.5 months.

The efficacy of the rituximab biosimilars in the matched analysis were observed. After 3-months following infusion, the overall response rate (ORR) was 76/142 (53.5%) for those receiving the originator and 47/74 (63.5%) for the patients receiving a biosimilar. The ORR at the 3-month mark was 26/34 (76.5%) for the Rixathon cohort and 35/68 (51.5%) for the reference product group. The reference product cohort had a remaining response of 24/57 (42.1%), whereas the Rixathon group had a remaining response of 18/28 (64.3%). The ORR for the Truxima group at 3 months was 21/40 (52.5%) vs 41/74 (55.4%)for the reference product group. At 12 months, the ORR for the Truxima group was 15/32 (46.8%) vs the 27/68 (39.7%) for the control group.

Patients receiving the reference product had similar responses compared with those who received the biosimilar.

Three patients receiving Truxima reported delayed effects and nonspecific adverse events after treatment. However, none were labeled severe nor needed hospitalization. 

The study was constrained by the absence of monitored B-cell depletion, which was not standard in France, thus, hindering comprehensive data. Additionally, the retrospective design and varied treatment timings among cohorts posed challenges to outcome completeness.

The study concluded, “The use of rituximab biosimilars for ITP treatment is a reliable option and offers hope for decreasing the cost of treatment for the challenged healthcare system.” 

Mageau A, Bonnotte B, Ebbo M, et al. Efficacy and safety of two rituximab biosimilars for treating immune thrombocytopenia: a reference-product matched study. 

. 2023;34(1):2200848. doi:10.1080/09537104.2023.2200848

Articles

A French study found that rituximab biosimilars, Rixathon and Truxima, were as effective and safe as the reference drug (Rituxan) in treating immune thrombocytopenia. 

Rituximab Biosimilars Effective in Treating Immune Thrombocytopenia

The Top 5 Biosimilar Articles for the Week of January 8, 2024. 

 found that combination therapies featuring trastuzumab biosimilars and other common cancer medicines were safe and effective in patients with breast cancer.

Number 4: Sarafraz K. Niazi, PhD, previews the new year and his hopes for the end of 

clinical efficacy testing for biosimilar approvals

 using examples from history of other scientific concepts that took time to gain traction.

 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.

Number 2: The regulatory structure of biosimilar development can be safely streamlined and made 

, wrote authors from Sandoz, Fresenius Kabi, Boehringer Ingelheim, and Samsung Bioepis in an opinion article published in BioDrugs.

 has announced that it will remove AbbVie’s blockbuster immunosuppressive drug Humira (adalimumab) from some of its preferred formulary drug lists in favor of more affordable biosimilar options for the drug. Starting April 1, 2024, Hyrimoz and an unbranded version of Humira manufactured by Sandoz will be covered across all CVS formularies, with branded and unbranded near copies of Humira manufactured by Biocon covered on some reimbursement lists.

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

The Top 5 Center for Biosimilars Articles for the Week of January 8

Pharmacist filling prescription in pharmacy | Image Credit: "Adobe Name" - stock.adobe.com

 administered to German and Swiss pharmacists in prepandemic 2020 had patterns of repetition in postpandemic 2022 regarding knowledge of biosimilars, the technical definition, specific substitution laws by country, and attitudes when substituting with biosimilars.

Researchers used an online English-language survey questionnaire to collect data on pharmacists from Germany and Switzerland about how their knowledge and dispensing frequency of biologics and biosimilars changed from before and after the pandemic. The study was aiming to analyze and review pharmacists’ perceptions regarding dispensing biosimilar medications instead of the reference product.

The survey links were sent to Swiss pharmacists in February 2020 and June 2022, while German pharmacists received the links in May 2020 and June 2022. The 17 items of topic included characteristics of participants, definition of biosimilars, frequency of dispensing biologics and biosimilars, attitudes towards biosimilars, substitution and interchangeability of biosimilars, and information sources on biosimilars. In 2022, the survey added the topic regarding the impact COVID-19 had on their perceptions of biologics and biosimilars.

In total, 764 pharmacists participated in the surveys (n = 390 in 2020; n = 374 in 2022). The surveys included statistical data-based time frames to assess dispensing frequency, grouped into “≥2 times a week” and “≤1 time a week”. The researchers used the abbreviations “DE” to reference German pharmacists and “CH” to reference Swiss pharmacists. Knowledge was determined using questions where participants had to correctly identify definitions for biologics and biosimilars as well as their countries’ substitution laws.

There were no major differences in frequency of dispensing biologics among German or Swiss participants from 2020 to 2022 (≥ 2 times a week: DE, 67.9% vs 53.3% and CH, 54.8% vs 56.4%; ≤ once a week: DE, 32.1% vs 46.7% and CH, 56.4% vs 43.6%, respectively). However, Swiss pharmacists increased their dispensing frequency of biosimilars from 2020 to 2022 to more than twice a week (9.7% to 23.8%; 

Both German and Swiss pharmacists did not have significant differences in knowledge of the term “biosimilars” in either year. In 2020, 41.7% of German pharmacists and 50% of Swiss pharmacists accurately defined the term biosimilars on the survey. All participants had at least heard of the term biosimilar. However, the most common misconception was a biosimilar labeled as a generic biologic (DE: n = 46 in 2020; n = 34 in 2022 vs CH: n = 28 in 2020; n = 59 in 2022).

Attitudes towards biosimilars, including familiarity of the term biosimilar, feeling sufficiently informed about biosimilars and informed on administering them, along with being confident in handling patient queries about biologic therapies, were unchanged in German and Swiss participants. However, Swiss pharmacists were more confident with handling patient questions about biosimilars than German participants in 2022. Swiss pharmacists also had higher confidence in biosimilar substitutions.

Knowledge on substitution laws and sources of information was unclear in both groups. More Swiss pharmacists were unaware of substitutions being permitted (2020: 37.1% vs 7.1%, respectively; 

< .005), whereas more German pharmacists thought substitutions were allowed for insulin products only (2020: 7.1% vs 1.6%, respectively; 

Regarding the impact of the COVID-19 pandemic, data showed most pharmacists indicated similar interest in biologics and biosimilars (DE: 60% vs CH: 55.5%), a similar working style (DE: 56% vs CH: 65.4%), and a similar confidence in counseling on biologics and biosimilars (DE: 61.3% vs CH: 57.4%). However, their knowledge as well as the feeling of readiness to assume more responsibility of biologicals and biosimilars in the future remained unchanged from before and after the pandemic.

The study was limited by the survey being available only in German and English in Switzerland, despite the country having 4 national languages. The sample size (390 in 2020, 374 in 2022) hindered generalizations. Introduced solutions like financial incentives may have biased results towards more interested and knowledgeable participants, potentially overstating pharmacists' knowledge compared to broader populations in Switzerland and Germany.

The researchers noted that the lack of knowledge and confidence is an issue that must be addressed when it comes to substitutions of drug originators.

Messner K, Eickhoff C, Schulz M, Allemann SS, Arnet I. Knowledge and attitudes of German and Swiss community pharmacists towards biologicals and biosimilars - a prospective survey before and after the COVID-19 pandemic. 

. 2023;23(1):1432. doi:10.1186/s12913-023-10475-x

A recent study found that the COVID-19 pandemic had little impact on the knowledge and attitudes of German and Swiss pharmacists regarding biologics and biosimilars between 2020 and 2022.

Examining Attitudes in German, Swiss Pharmacists on Biosimilar Dispensing Pre- and Post Pandemic

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.

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

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

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.