Justina Petrullo

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 May 22nd, 2023.

Number 5: Although the FDA has consistently edited its testing guidelines for biosimilar developers over the years, 

 and time-consuming. Sarfaraz K. Niazi, PhD, offered the FDA and companies a plan of action for reducing clinical testing expenses for biosimilar products.

 said Sanofi’s biosimilar SAR341402, approved in June 2020 by the European Medicines Agency for use in insulin pumps, had similar stability compared with the originator under stress conditions in their experiments.

Number 3: Amneal Pharmaceuticals announced the launch of its 

, Fylnetra (pegfilgrastim-pbbk), for the treatment and prevention of febrile neutropenia, making it the sixth biosimilar referencing Neulasta to enter the US market.

Number 2: As Celltrion Healthcare announced the 

 version of Remsima (Remsima SC) in Brazil, the company shared the phase 3 plan for its ocrelizumab biosimilar to treat multiple sclerosis (MS).

Number 1: As Sandoz and Just-Evotec Biologics 

, Celltrion secured tender wins in Italy and Belgium, and Alvotech began testing its golimumab biosimilar in patients with rheumatoid arthritis.

To read all of these articles and more, visit 

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Here are the top 5 biosimilar articles for the week of May 22, 2023.

The Top 5 Biosimilar Articles for the Week of May 22

Recent data could contribute to discussions on generating more transparency about global approvals of follow-on biologics and supporting access to high-quality biosimilars in countries around the world, according to a study published in 

 as an umbrella term for FDA-classified biosimilars as well as biologics that are biosimilars by definition but are not officially declared as such in the United States (eg, Basaglar, Granix). This is because they were approved before the establishment of the biosimilar approval pathway (the Biologics Price Competition and Innovation Act). These products, sometimes called authorized generics, may be classified as biosimilars in other global markets.

This study was conducted because present knowledge is limited about which manufacturers are active globally in biopharmaceutical product development and how many unique follow-on biologics are approved in international markets.

First, researchers wanted to provide a cross-sectional overview of manufacturers of follow-on biologics approved in 15 countries from different regions of the world, and in 5 major biosimilar markets with long-established biosimilar frameworks.

“The biosimilar approach involves a robust comparability exercise to prove that the follow-on biologic is clinically equivalent to the innovator product and does not compromise on safety and efficacy,” the researchers wrote.

Next, national drug databases were screened to distinguish follow-on biologics and their manufacturers approved in 15 countries in Asia, Africa, Latin America, and the rest of the globe, and 5 major biosimilar markets: the European Union (including the United Kingdom), the United States, Canada, Australia, and Japan. 

Then, the study detected 304 follow-on biologics from various manufacturers for 18 active substance classes included in the analysis. Of these, 67 products were approved as biosimilars in at least 1 of the 5 major biosimilar markets. This study found that the bulk of follow-on biologics were only approved in their respective country of manufacturing. A small number of these, primarily from India and Argentina, supplied their products to other parts of the world. 

“As some countries have less stringent regulatory approaches for biosimilars, or have only recently implemented biosimilar guidance in line with World Health Organization (WHO) standards, follow-on biologics could have been approved that would not be considered biosimilars according to the [WHO] standards,” said the researchers.

Researchers expect that a significant portion of the 237 follow-on biologics, particularly recent approvals, can be considered biosimilars according to WHO biosimilar standards despite not being available as biosimilars in any of the 5 major biosimilar markets.

The authors made a number of takeaways and policy recommendations based on the results, including:

More globally concerted efforts are needed to improve transparency about manufacturing and approvals of follow-on biologics.

The lack of global understanding of follow-on biologics could have severe implications for various stakeholders, including patients.

Several implications from a national perspective were highlighted, especially regarding clinical practice and pharmacovigilance.

The use of different brand names in different countries could create challenges for the identifiability of follow-on biologics, especially for drug safety monitoring.

Using identical international nonproprietary names for biosimilars and noninnovator biologics (ie, follow-on biologics that cannot be considered biosimilars according to the WHO) could create switching challenges for clinical practice, especially if the products coexist in the same market.

The WHO holds an important role as a neutral and global institution to collect and provide information on approvals of all follow-on biologics found in the global market.

Advocacy for greater regulatory reliance to facilitate faster and broader access to high-quality biosimilars worldwide could help speed up access in low- and middle-income countries.

Based on the findings of this study, the researchers recommend follow-up studies to analyze the possible existence of noninnovator biologics in global markets.

“In the end, this study wants to contribute to discussions on how to improve and accelerate global access to safe and high-quality biosimilars that are imperative for healthcare systems around the world,” the researchers concluded.

This study only provides a glimpse of approvals of follow-on biologics. The information provided is dependent on the completeness of information databases and other regulatory documents, and the available information on initial approval dates of individual follow-on biologics was limited, which could all be considered limitations.

Klein K, Gencoglu M, Heisterberg J, Acha V, Stolk P. The global landscape of manufacturers of follow-on biologics: an overview of five major biosimilar markets and 15 countries. 

 2022;37:235-245. doi:10.1007/s40259-022-00568-0

Articles

Findings from a recent study emphasize the need for improvement and changes regarding follow-on biologics and biosimilars in the global biosimilar market.

Recent Findings Highlight Need for Policy Changes for Biosimilars, Follow-on Biologics 

Here are the top 5 biosimilar articles for the week of May 15th, 2023.

Number 5: Colby Evans, MD, a dermatologist and co-author of an 

 supplement “Biosimilars for Immune-Mediated Inflammatory Diseases: 2022 Update" shared the 

 on using biosimilars to treat inflammatory conditions.

study including 2 years of real-world evidence

 (RWE), patients with rheumatoid arthritis (RA) who were switched from originator rituximab (Rituxan) to GP2013, a rituximab biosimilar, experienced positive results and maintained clinical outcomes.

FDA has consistently edited its testing guidelines

 for biosimilar developers over the years, clinical testing is still very expensive and time-consuming. Sarfaraz K. Niazi, PhD, offered the FDA and companies a plan of action for reducing clinical testing expenses for biosimilar products.

 comparing the tocilizumab biosimilar candidate LZM008 to the reference product (Actemra) found pharmacokinetic (PK) parameters within the bioequivalence margins and similar immunogenicity and safety in healthy participants.

Number 1: In the first edition of Samsung Bioepis’ Biosimilar Market Report, the company outlined the 

current state of the US biosimilars market

 and how increasing adoption has had an impact on pricing changes for biosimilars and their reference products.

Here are the top 5 biosimilar articles for the week of May 15, 2023.

The Top 5 Biosimilar Articles for the Week of May 15

Here are the top 5 biosimilar articles for the week of May 8th, 2023.

study including 2 years of real-world evidence (RWE)

, patients with rheumatoid arthritis (RA) who were switched from originator rituximab (Rituxan) to GP2013, a rituximab biosimilar, experienced positive results and maintained clinical outcomes.

Number 4: The authors of what they say is 

 comparing the trastuzumab biosimilar SB3 to the reference product (Herceptin) in HER2-positive breast cancer found “no clinically meaningful difference” between the biosimilar and the reference product.

investigating the use of bevacizumab biosimilars

 found that despite lingering concerns about their usage for extrapolated indications, bevacizumab biosimilars are regularly used in metastatic colorectal cancer (mCRC) even though clinical tests only evaluate them in patients with lung cancer.

Number 2: At the 2023 Association for Research in Vision and Ophthalmology Annual Meeting, Samsung Bioepis shared 

comparable safety, efficacy, and immunogenicity

 data through 1 year between its aflibercept biosimilar (SB15) and the originator (Eylea).

 how pharmacodynamic (PD) markers may be better than clinical efficacy testing for predicting whether a biosimilar is equally as safe and effective as its reference product, in his latest column.

Here are the top 5 biosimilar articles for the week of May 8, 2023.

The Top 5 Biosimilar Articles for the Week of May 8

Here are the top 5 biosimilar articles for the week of May 1st, 2023.

Number 5: Samsung Bioepis shared positive 1-year results from a phase 3 trial 

 between the company’s aflibercept biosimilar and the originator (Eylea) at the 2023 Association for Research in Vision and Ophthalmology Annual Meeting.

Number 4: In April, biosimilars to treat rheumatic conditions had some progress, as well as some setbacks, and 

 that switching from originators to biosimilars is safe and effective but warned about the nocebo effect.

, Vegzelma, a bevacizumab biosimilar, launched in the United States; 2 biologics license applications (BLAs) for biosimilars were accepted for review by the FDA; and China’s regulatory agency approved a denosumab biosimilar.

Number 2: Nonmedical switches from Humira (reference adalimumab) to a biosimilar or an adalimumab biosimilar to another biosimilar 

 responses, suggesting that more communication between providers and patients is needed, according to a real-world analysis.

Number 1: Sarfaraz K. Niazi, PhD, dove into 

 may be better than clinical efficacy testing for predicting whether a biosimilar is equally as safe and effective as its reference product, in his latest column.

Here are the top 5 biosimilar articles for the week of May 1, 2023. 

The Top 5 Biosimilar Articles for the Week of May 1

Intravitreal injection of innovator ranibizumab (Lucentis) and biosimilar ranibizumab (Razumab) displayed similar efficacy and safety in the eyes of Indian patients with neovascular age-related macular degeneration (nAMD), according to a study published in 

No significant differences were found in either the primary or secondary end points, demonstrating the biosimilarity between the originator and biosimilar products.

Researchers of the study noted that “FDA approval of SB11, a biosimilar ranibizumab, is perhaps the beginning of a new paradigm in the use of biosimilar ranibizumab in the treatment of retinal vascular disease in general and nAMD in particular” due to the financial savings and safety and efficacy profile of the drug.

Ranibizumab products are anti–vascular endothelial growth factor (VEGF) agents that are used to treat several ophthalmic conditions, including nAMD, diabetic retinopathy, macular edema, and myopic choroidal neovascularization.


Researchers were trying to observe the treatment outcomes of Lucentis vs Razumab in a retrospective observational study among patients with nAMD who were administered 3 loading doses. Primary outcome measures were change in best corrected visual acuity (BCVA) and central macular thickness (CMT) in addition to safety analysis. Secondary outcome measures were subretinal fluid (SRF) and intraretinal fluid (IRF) changes. The BCVA was evaluated using value scores from the Logarithm of the Minimum Angle of Resolution (

nAMD is a major contributor to vision loss among people over 50, with prevalence increasing constantly with age. It’s been estimated that the number of nAMD-afflicted patients will reach 288 million by 2040. 

“Application of anti-VEGFs has significantly reduced almost certain blindness and has resulted in improved visual acuity in nAMD patients,” the researchers wrote. Currently, there are no comparative studies displaying the efficacy of the biosimilar with the innovator molecule with up to 12 months follow up.

In the study, inclusion criteria were confirmed in 164 (60.74%) eyes and a total of 87 eyes were treated with the innovator and 77 with the biosimilar.

The baseline BCVA was a mean (SD) logMAR value of 0.57 (0.27) in the innovator group and 0.61 (0.25) in the biosimilar group. At 3, 6, 9, and 12 months, the mean (SD) logMAR value in the innovator group was 0.27 (0.22) (

 < .0001), respectively. In the biosimilar group, the mean (SD) baseline logMAR value was 0.24 (0.16) at 3 months, 0.27 (0.16) at 6 months, 0.34 (0.17) at 9 months, and 0.38 (0.18) at 12 months (

The baseline CMT was 420.39 (54.45) μm in the innovator group and 47.82 (53.07) μm in the biosimilar group. At 3, 6, 9, and 12 months, the CMT in the innovator group decreased to 258.28 (20.4) μm, 268.38 (19.5) μm, 269.51 (32.41) μm, and 278.28 (16.56) μm, respectively (

< .0001 for all). In the biosimilar group, the CMT dropped to 258.84 (17.47) μm at 3 months, 265.69 (17.29) μm at 6 months, 273.64 (23.13) μm at 9 months, and 283.09 (19.66) μm at 12 months (

Both fluid compartments (SRF and IRF) displayed similar improvement starting from month 3 after the first 3 loading doses. The comparable efficacy of the originator to that of the biosimilar is further supported by a similar number of injections needed by the 2 drugs over the same period to reach similar clinical improvement and a similar profile of adverse events in both groups.

Then, researchers highlighted that past short-term results are in support of the results seen in this study. Razumab is around 30% to 40% less expensive than Lucentis in India. A PRN regimen with strict follow-up in resource-poor settings can offer comparable results with much reduced expenses if a fixed or a treat-and-extend regimen is not available. An additional reduction in the expenses can be brought about with the use of BRM.

Some limitations of the study included its retrospective design and pro re nata protocol after 3 loading doses and a fairly small data set which may have made it difficult to comment on adverse events.

The researchers concluded with “long-term prospective studies will enable us to better understand the efficacy and safety of BRM in nAMD management.”

Chakraborty D, Mondal S, Boral S, et al. Biosimilar versus innovator molecule of ranibizumab in neovascular age-related macular degeneration (The BALANCE Trial): real-world evidence. 

. 2023;17:1067-1076. doi:10.2147/OPTH.S407219

Biosimilar ranibizumab showed similar efficacy and safety in a recent study of the eyes of Indian patients with neovascular age-related macular degeneration.

Biosimilar Ranibizumab Displays Comparable Safety, Efficacy to Lucentis

In recent years, Canada and other countries that require justifications for high-priced biologics have begun to shift patients to lower-cost biosimilars, known as nonmedical switching. Biosimilars for infliximab, used in inflammatory bowel disease (IBD), which encompasses Crohn disease (CD) and ulcerative colitis (UC), have become increasingly available.

The inclusion of biosimilars in economic evaluations for pricing decisions has been lacking, but researchers writing in 

 said that examining biologic drug price in a sensitivity analysis provided insight into the cost-effectiveness of biosimilar alternatives.

The authors screened studies using databases such as MEDLINE, Embase, Healthstar, Allied and Complementary Medicine, and more; economic assessments of infliximab for adult or pediatric CD and/or UC published from 1998 through 2019 where drug price was varied in sensitivity analysis were included. Eligible studies could include originator infliximab, biosimilar infliximab, or both, either as an exclusive comparator or used with other therapies; only economic evaluations that contained a 1-way sensitivity analysis of price could be included.

Researchers included each jurisidction’s stated willingness-to-pay threshold for the cost-effectiveness of infliximab.

Out of 844 studies screened, 31 were analyzed. Most studies (58%) showed an incremental cost-effectiveness of infliximab in gastrointestinal diseases that surpassed the WTP threshold.

However, infliximab showed favorable cost-effectiveness at a price ranging from C$66 (US$49) to C$1260 (US$930.13 per vial, depending on the location.

In many other countries, drugs are assessed for their therapeutic benefit relative to existing products, and depending on the outcome of that assessment, price ceilings are set accordingly.

But mandatory switching policies ordering the use of lower cost 

 in patients with IBD have incited worries for patients who prefer the original biologic.

The researchers of the current study said alternative pricing strategies and treatment access could be considered to allow patients with IBD to continue access to their current medications.

Bashir NS, Hughes A, Ungar WJ. Infliximab pricing in international economic evaluations in inflammatory bowel disease to inform biologic and biosimilar access policies: a systematic review. 

A recent systematic review looked at the impact of different prices for infliximab in inflammatory bowel disease and the willingness-to-pay threshold around the world.



Price Variation in Economic Evaluations of Infliximab Could Influence Biosimilar Access

Here are the top 5 biosimilar articles for the week of April 17th, 2023.

Number 5: The Committee for Medicinal Products for Human Use 

 for an eculizumab biosimilar, and a biologic license application for a bevacizumab biosimilar was accepted in Brazil.

Number 4: A retrospective real-world study assessing patient outcomes related to switching from reference rituximab (Rituxan) to a biosimilar version (Truxima) found that transitioning between the products was 

 and did not result in a change in adverse events.

Number 3: Celltrion Healthcare shared data from a phase 3 clinical trial confirming that its omalizumab biosimilar had 

Number 2: In a complete response letter (CRL) for Alvotech, the FDA cited “deficiencies” in the company’s manufacturing facility during a reinspection, further 

 for the ninth adalimumab biosimilar until potentially June 2023.

Number 1: The misconceptions about disposable bioreactors' lifecycle are gone; the era of hard-piped, giant, stainless-steel tanks for biosimilar development is history now, 

Here are the top 5 biosimilar articles for the week of April 17, 2023.

The Top 5 Biosimilar Articles for the Week of April 17

Multiple successive switches from originator infliximab (Remicade) to biosimilars were safe and effective in patients with inflammatory bowel disease (IBD), regardless of the number of infliximab switches (single, double, and triple), according to a 

. IBD is an umbrella term for ulcerative colitis and Crohn disease.

This study was conducted because there is scarce data on multiple switching, though it is known that switching from originator infliximab to biosimilar infliximab is safe and effective. “In the present economic climate with multiple biosimilars available at competitive prices, data about multiple biosimilar switches is of increasing importance,” said the researchers.

An IBD unit in Edinburgh had previously undertaken 3 switch programs as biosimilar prices dropped: originator infliximab to CT-P13 (sold as Remsima in Europe) in 2016; CT-P13 to SB2 (sold as Flixabi in Europe) in 2020; and SB2 to CT-P13 in 2021. In ex-EU regions (such as the United States, Canada, and Australia), SB12 is marketed under the brand name Renflexis by Organon.

The primary endpoint of the current study was to assess CT-P13 persistence after an elective switch from SB2 in 297 patients. Secondary endpoints comprised persistence stratified by the number of biosimilar switches (single, double, and triple), safety, and effectiveness.

Patients were included in the study if they had 3 doses of SB2.

Of the total, 196 patients had Crohn disease (66%) and 101 had IBD (34%). They were followed for a median of 7.5 months (interquartile range, 6.8-8.1 months).

Patient demographics and IBD characteristics were obtained from electronic medical health records.

Data collection included clinical disease activity, C-reactive protein (CRP) levels, fecal calprotectin, infliximab trough/antibody levels, and drug survival.

The switch to CT-P13 from SB2 was the third, second, and first infliximab change for 67/297 (22.5%), 138/297 (46.5%), and 92/297 (31%) of the cohort, respectively.

Nearly 91% of patients stayed on infliximab during follow-up. Switch number was not independently associated with infliximab persistence after adjusting for cofounders.

Remission rates were comparable at baseline, week 12, and week 24 as measured by clinical disease activity, CRP level, and fecal biomarker level.

Researchers said that the duration of infliximab, rather than the number of biosimilar switches, are an independent predictor for infliximab persistence. They also added that duration and number of switches are correlated, saying that this might be explained by the known disconnect between symptoms and active inflammation in IBD and by collinearity in the multivariable model.

In 5 patients, 6 adverse events were reported, and included psoriatic reaction, squamous cell carcinoma of the tonsil, arthralgia, severe COVID-19 infection necessitating intensive care unit (ICU) hospitalization, heart failure necessitating ICU admission, and mild skin reaction. Three of the adverse events were defined as severe, leading to drug discontinuation.

While immunogenicity has been a concern in biosimilar switching, the researchers noted this study and past research has not found this to be the case when involving multiple switching.

This is the first study analyzing the efficacy and safety of 3 successive switches in patients with IBD receiving infliximab, the authors said. Some limitations of the study were that the study design did not include a control arm that continued SB2, hindering the comparison of effectiveness and safety between groups. Baseline characteristics were not comparable between subgroups (ie, different duration), and there was some missing data that may have resulted in a conservative estimate of effectiveness outcomes.

The researchers concluded that multiple successive switches from originator infliximab to biosimilars appear effective and safe, regardless of the number of switches. Importantly, these results can contribute to saving health care costs.

“These findings are of major socioeconomic importance, especially in low and middle‐income countries where the access to healthcare may be limited,” they said.

Gros B, Plevris N, Constantine-Cooke N, et al. Multiple infliximab biosimilar switches appear to be safe and effective in a real-world inflammatory bowel disease cohort. 

. 2023;11(2):179-188. doi:10.1002/ueg2.12357

A retrospective study in Scotland found that multiple successive changes from originator infliximab to biosimilars seem to be safe and effective in patients with inflammatory bowel disease (IBD), irrespective of the number of switches.

Multiple Infliximab Biosimilar Switches Appear Safe, Effective for Patients With IBD

Here are the top 5 biosimilar articles for the week of April 10th, 2023.

Number 5: Celltrion Healthcare shared data from a phase 3 clinical trial confirming that its 

omalizumab biosimilar had comparable safety and efficacy

, neurologists in Europe reported feeling positive about the biosimilars for multiple sclerosis (MS) coming down the pipeline, showing that industry-wide education efforts and experience with biosimilars are working to instill greater confidence in these products.

Number 3: A retrospective study from India found that Razumab, a ranibizumab biosimilar, was 

safe and effective to use in infant patients

 with retinopathy of prematurity. This is the first analysis assessing the clinical outcomes associated with the biosimilar in this population.

Number 2: STADA Arzneimittel and Xbrane Biopharma 

 of Ximluci, a ranibizumab biosimilar referencing Lucentis approved to treat ophthalmic conditions, across the European Union.

gained another high-concentration adalimumab biosimilar

 with the approval of Sandoz’ Hyrimoz HCF and the FDA accepted a biologics license application for a trastuzumab biosimilar (HLX02).

Here are the top 5 biosimilar articles for the week of April 10, 2023.