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 June 26th, 2023.

 of biosimilars can assist in promoting their use and defeat misconceptions and misinformation related to generic drugs and biosimilars.

 find that a rituximab biosimilar, BCD-020, was safe and effective in pediatric patients with lupus nephritis.

Number 3: The ranibizumab biosimilar XSB-001 (Ximluci) 

 to the originator (Lucentis) in a phase 3 trial in neovascular age-related macular degeneration (nAMD).

Number 2: An analysis of 25 studies finds adalimumab, infliximab, and etanercept biosimilars 

 in comparison with their originators in the treatment of rheumatoid arthritis.

Number 1: In his latest column, Sarfaraz K. Niazi, PhD, 

 about biosimilar development and expresses how companies can seize new opportunities to save the US biosimilar market and generate profit.

To read all of these articles and more, visit 

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Here are the top 5 biosimilar articles for the week of June 26, 2023.

The Top 5 Biosimilar Articles for the Week of June 26

Cancer treatment, pediatric population, and coverage restriction of reference products were discovered as some of the most significant factors associated with biosimilar coverage decisions by commercial health plans in the US relative to their reference products, 

Although biosimilars have been introduced with the aim of competing with expensive biologic therapies, their adoption has been more gradual than expected and caused restricted gains in efficiency. The study authors’ aimed to discover factors associated with payers coverage of biosimilars compared to their originators in the United States.

The study authors identified 1181 coverage decisions for 19 commercially available biosimilars, representing 7 reference products and 28 indications from the Tufts Medical Center Specialty Drug Evidence and Coverage database. They summarized the coverage restrictiveness as a binary variable based on if the product is covered by the health plan, and if so, the difference of payers’ line of therapy between the biosimilar and its amount of possible coverage drivers.

Compared with reference products, health plans dictated coverage exclusions or step therapy limitations on biosimilars in 229 (19.4%) decisions.

Plans were more likely to restrict biosimilar coverage for pediatric populations (OR, 11.558; 95% CI, 3.906-34.203), diseases with US prevalence higher than 1,000,000 cases (OR, 2.067; 95% CI, 1.060-4.029), and if the plan did not contract with 1 of the 3 major pharmacy benefit managers (PBM; OR, 1.683; 95% CI, 1.129-2.507).

In comparison with the reference product, plans were less likely to enforce restrictions on the biosimilar–indication pairs if the biosimilar was indicated for cancer treatments (OR, 0.019; 95% CI, 0.008-0.041), and if the product was the first biosimilar to market (OR, 0.225; 95% CI, 0.118-0.429). Additionally, payers were less likely to restrict biosimilars that:

Had 2 competitors, including the reference product (OR, 0.060; 95% CI, 0.006-0.586)

Could generate annual list price savings of more than $15,000 per patient (OR, 0.171; 95% CI, 0.057-0.514)

Referenced an originator that was already restricted by the plan (OR, 0.065; 95% CI, 0.038–0.109)

Did not have a cost-effectiveness measure available (OR, 0.066; 95% CI, 0.023-0.186)

Although health plans were more likely to set restrictions on biosimilars for pediatric use, past studies have suggested the reverse for all specialty drugs. The authors called for future investigations to focus on this topic.

In the model used in this study, the lack of cost-effective evidence was significantly associated with less limited coverage, which might mirror a concern about the limited evidence on value or a worry about low value because of possible publication bias.

“In either case, when the value of the reference biologic has not been formally established, health plans favor biosimilars,” said the study authors.

This is the first study that evaluates the factors associated with US commercial health plan biosimilar coverage.

The study had a few limitations, including that the study authors only considered biosimilars that were authorized through the 351(k) abbreviated pathway in their analysis. Also, they determined annual savings using list prices, which might not show the true savings for commercial health plans because plans usually acquire biologics at prices lower than their list prices.

“Future research is needed to identify the effects of such restrictions and other market forces (such as price negotiations by commercial plans and PBMs) on the efficiency of the market and resulting patient access to costly biologic therapies,” concluded the study authors.

Yu, T., Jin, S., Li, C. Chambers JD, Hlávka JP

 Factors associated with biosimilar exclusions and step therapy restrictions among US commercial health plans. 

 2023;37(4):531-540. doi:10.1007/s40259-023-00593-7

Articles

It was found that cancer treatment, pediatric population, and coverage restriction of reference products were revealed as some of the strongest factors associated with biosimilar coverage decisions by US commercial health plans relative to reference products.

Payers Reveal Most Significant Factors Impacting Biosimilar Coverage Decisions 

Here are the top 5 biosimilar articles for the week of June 19th, 2023.

 that acts as an invitation to biosimilar developers to decrease the cost of testing, potentially opening the door for companies to reduce nonclinical testing of biosimilars entirely.

Number 4: A survey of patients with rheumatoid arthritis found that those who had 

 reported higher disease severity, poorer treatment adherence, and poorer quality of life compared with patients who stayed on the reference product, highlighting the dangers of the nocebo effect.

Number 3: After 8 years of trastuzumab biosimilar competition and slow uptake, 

a new report showed that trastuzumab biosimilar

 discounts from the reference product (Herceptin) doubled between 2019 and 2022.

SmithRx became the first pharmacy benefit manager

 (PBM) to announce it will cover Yusimry, 1 of 9 FDA-approved adalimumab biosimilars; Celltrion Healthcare received a thumbs-up from the FDA to test a biosimilar for Ocrevus; Alvotech and Teva Pharmaceuticals settled with Johnson & Johnson over their biosimilar referencing Stelara.

Number 1: Coherus Biosciences and AbbVie 

 regarding Coherus’ partnership with the Mark Cuban Cost Plus Drug Company and an adalimumab biosimilar, and Celltrion and Bio-Thera Solutions expanded their respective partnerships to include more biosimilar products.

Here are the top 5 biosimilar articles for the week of June 19, 2023.

The Top 5 Biosimilar Articles for the Week of June 19

Advancing pharmacists’ knowledge to promote the use of 

 can help conquer misconceptions relating to generic drugs and biosimilars in Lebanon, according to 

Study authors recommend that health care stakeholders concentrate on cultivating good understanding among pharmacists to improve medication access.

The study was conducted because pharmacists’ knowledge of the differences in the traits between generic drugs and biosimilars is vital to ensure good practice and minimized pharmaceutical costs. The study authors were trying to analyze community pharmacists’ comprehension and awareness of using and substituting biosimilar and generic medications.

“The unified medical prescription allowed Lebanese pharmacists to substitute drugs taking into account their price and availability. Good knowledge and practice among pharmacists of the differences in the characteristics between generic drugs and biosimilars are crucial since they play a key role in clinical practice,” said the study authors.

Biosimilars require clinical switching evidence to support their interchangeability with biologics.

First, a uniform survey distributed to 75 pharmacists was used to collect data, and a pilot cross-sectional study was conducted over 2 months (August-September 2022) addressing community pharmacists in their work environments. Following survey data collection, a knowledge score was generated by calculating several individual scores of statements about generic drugs and biosimilars.

In general, pharmacists possessed moderate to low knowledge scores, especially with the statements tackling biosimilars. No significance was noted between these scores and their general traits. Most pharmacists decided to substitute generic drugs if the brand wasn’t available, while the doctor’s approval was imperative for biosimilar switching. dMost participants discerned equal effectiveness of generic drugs but similar to a lower one for biosimilars compared to the reference drug. Pharmacists emphasized the need to include generic drugs and biosimilars in the continuing education program and workshops.

Most pharmacists noted that they substituted for generic drugs if the brands weren’t available, or the patients asked for less-costly options. Data were collected during the COVID-19 pandemic and Lebanon’s economic crisis, which could be an explanation.

Despite this, over 50% of the pharmacists agreed to change a biological reference drug to its biosimilars only with the doctor’s approval, connecting either appropriate knowledge to behavior or a potential lack of knowledge to the referral of other health care providers.

“Community pharmacists’ knowledge of the differences between generic drugs and biosimilars should be improved, since it was found to be associated with patients’ acceptance to buy and substitute for generic drugs,” said the study authors.

To promote the use of biosimilars, enhancing pharmacists’ knowledge of biosimilars can help surmount misconceptions and misinformation about generic drugs and biosimilars.

Some limitations of the study were that the sample included more women than men, and participants were mostly young, which might have restricted their knowledge to recent information.

“Further investigation on a bigger sample size is recommended to evaluate the knowledge gaps in assessing the differences between generic drugs and biosimilars,” concluded the study authors.

Awada S, Sayah R, Mansour M, Nabhane C, Hatem G. Assessment of community pharmacists' knowledge of the differences between generic drugs and biosimilars: A pilot cross-sectional study. 

. Published online April 17, 2023. doi:10.1177/27550834231167049

Enhancing pharmacists’ knowledge of biosimilars can assist in promoting their use and defeat misconceptions and misinformation related to generic drugs and biosimilars.

Increasing Pharmacists’ Knowledge of Biosimilars Can Quell Misconceptions, Misinformation

Here are the top 5 biosimilar articles for the week of June 12th, 2023.

 extended their partnership to commercialize 5 biosimilar candidates across Europe.

Number 4: Infliximab (IFX) biosimilar SB2 was 

 in IFX-naïve patients and those who switched from a prior IFX reference or biosimilar.

the 340B program is slowing uptake of biosimilars

 by incentivizing use of more expensive biologics.

, an online pharmacy dedicated to increasing access to lower-cost prescriptions, partnered with Coherus Biosciences to distribute Yusimry, a biosimilar referencing Humira. It’s the first time the pharmacy has added a biosimilar to its list of drugs.

Here are the top 5 biosimilar articles for the week of June 12, 2023.

The Top 5 Biosimilar Articles for the Week of June 12

Routine infliximab (IFX) biosimilar SB2 therapy was observed to be safe and effective in IFX-naïve patients and in patients changed from a prior IFX reference or biosimilar, according to a study published in 

The PERFUSE study was conducted to evaluate the 12-month persistence, effectiveness, and safety effects of routine SB2 treatment in patients who have chronic inflammatory rheumatic disease.

“The marketing authorization of SB2 was based on demonstration of comparable physicochemical and biological characteristics, pharmacokinetic similarity in healthy patients, and comparable efficacy and safety in patients with RA [rheumatoid arthritis] compared with IFX ref,” said the researchers.

The PERFUSE trial was a noninterventional study of 1233 adult patients (rheumatology, n = 496; irritable bowel disease, 

= 737) receiving periodic IFX biosimilar SB2 therapy.

First, patients with a diagnosis of RA, psoriatic arthritis, or axial spondyloarthritis (axSpA) were accredited to 1 of 3 study cohorts according to whether SB2 treatment started after September 2017 had been the first IFX treatment (IFX naïve) or followed a shift from reference IFX (IFX ref) or another IFX biosimilar (IFX bs). Effects to month 12 (mean [SD] value 2) was composed of persistence (primary outcome), SB2 dose, disease status, immunogenicity, and safety.

During month 12, persistence on SB2 in the IFX-naïve, IFX ref, and IFX bs cohorts, respectively, consisted of the following 59% (95% CI, 36.1%-76.2%), 75% (95% CI, 57.5%-86.1%), and 85% (95% CI, 69.6%-93.0%) for RA (n = 98); 64% (95% CI, 34.3%-83.3%), 87% (95% CI, 65.6%-95.7%), and 83% (95% CI, 60.0%-93.1%) for PsA (n = 62); and 56% (95% CI, 44.4%-66.5%), 80% (95% CI, 70.8%-86.1%), and 80% (95% CI, 72.5%-85.6%) for axSpA (n = 336).

Disease activity was commensurate at baseline and month 12 in both the IFX ref and bs subgroups of all cohorts by indication. No concerns of immunogenicity and new safety signals were detected. In addition, during the 12-month time period, the last month from the PERFUSE study rheumatology cohorts showed no clinically meaningful differences in clinical effectiveness during a 12-month period in patients switched from IFX ref or IFX bs to SB2.

“More than 75% of patients who transitioned from prior IFX and continued on SB2 treatment to month 12 post SB2 initiation showed no meaningful difference in clinical measures, regardless of whether they received prior IFX ref or IFX bs. More than 56% of IFX-naïve patients continued on SB2 treatment at month 12 with no changes in dosing regimen,” said the researchers.

In the PERFUSE study, the persistence rate was seen to be aligned with the reported persistence rate for biosimilar CT-P13, as well as the discontinuation rate communicated for patients started on IFX ref, indicating that although a nocebo effect can’t be ruled out, this did not have a meaningful impact in the studied population.

Following this, the researchers said, “In PERFUSE, the most frequent reason for discontinuation was physician decision following loss of response.”

Since concerns remain for some prescribers about switching to biosimilars, the researchers determined that it’s important to review immunogenicity data in the real-world setting. Even though routine immunogenicity testing was sporadic in the study population, the results did not show an increased risk of immunogenicity to IFX after SB2 initiation.

The authors described no increased risk of immunogenicity as a result of 1 switch or successive switches to IFX bs, which confirm PERFUSE timing so far.

Some limitations of this study include the small sample size and that no patient control groups were present of patients staying on reference or other IFX bs because all eligible patients had been moved to SB2.

“Long-term studies and real-world studies using SB2 for the treatment of patients with chronic inflammatory rheumatic diseases will increase our understanding of the clinical utility of biosimilars and their potential to pave the way for increased access to treatment,” concluded the researchers.

Fautrel B, Bouhnik Y, Dieude P, et al. Real-world evidence of the use of the infliximab biosimilar SB2: data from the PERFUSE study. 

. Published online April 17, 2023. doi:10.1093/rap/rkad031

Infliximab (IFX) biosimilar SB2 was shown to be safe and effective in IFX-naïve patients and those who switched from a prior IFX reference or biosimilar. 

Infliximab Biosimilar Found to Be Safe, Effective

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

Number 5: Over the course of May, the immunology biosimilar space bloomed, with a European approval, 

, more clinical trial updates, and insights into the industry from multiple immunology experts.

 to commercialize 5 biosimilar candidates across Europe.

 to Samsung Bioepis' biosimilar referencing Soliris (eculizumab). The product, dubbed Epysqli is the first hematology biosimilar from Samsung Bioepis to be approved in the European Union.

Amgen has settled with Johnson & Johnson (J&J)

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

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

The Top 5 Biosimilar Articles for the Week of June 5

The introduction of biosimilars to the Spanish Health System (SNHS) of Spain would create 

 in the pharmacological budget to promote biological drugs from the first year, according to a study published in the 

This study was conducted to evaluate the economic impact of introducing bevacizumab biosimilars in the systemic treatment of patients with cancer in the SNHS.

“Cancer is the second leading cause of death in Europe and one of the diseases with the greatest impact on public health,” said the researchers.

Bevacizumab was the first approved angiogenesis inhibitor to treat cancer tumors and therefore expanded the line of biological treatments against cancer. It’s estimated that about 30% of the pharmaceutical budget in Europe is set aside for the acquisition of biological drugs. Patent expirations for originator biological drugs has given rise to biosimilar drug alternatives.

First, a 3-year budget impact analysis model was adapted to estimate biosimilar introduction cost of bevacizumab in the SNHS for the adult population eligible to receive bevacizumab treatment. Values for the estimation of the population were acquired through the literature and validated by an expert panel.

Next, in the analysis, only pharmaceutical costs acquired through official databases were considered. A sensitivity analysis was performed to examine the strength of the model.

The launch of bevacizumab biosimilars would produce a yearly cost saving of €11,558,268 ($12,394,104; −5.1%) for the first year with a penetration share of biosimilars from 30%, €29,126,373 ($31,232,647; −8.5%) for the second year with a share of 50% and €52,361,778 ($56,148,320; −13.6%) for the third year with a share of 80%. 

The total pharmaceutical costs of the plan without biosimilars are €227,033,352 ($243,451,269) for the first year, €342,663,209 ($367,442,899) for the second year and €385,013,076 ($412,855,297) for the third year. Conversely, the pharmaceutical costs of the plan with bevacizumab biosimilars are €215,475,084 ($231,057,165), €313,536,836 ($336,210,252) and €332,651,297 ($356,706,976) for years 1, 2 and 3, respectively.

Upon examination, a decrease was seen in the costs of all cancers treated with bevacizumab per patient after the introduction of biosimilars. Indications that needed higher doses saw a greater impact because of the lower price of biosimilars with bevacizumab for indications such as metastatic, unresectable or relapsed non-small cell lung cancer (mNSCLC), except for squamous cell histological type, and advanced and/or metastatic renal cell carcinoma, stage 3B. However, for indications where a greater number of patients are treatment candidates for either reference bevacizumab or its biosimilars, such as stage 3C and 4 epithelial ovarian, Fallopian tube or peritoneal cancer and metastatic colorectal cancer (mCRC), showed high-cost differences.

“In the first year, and with a penetration rate of 30.0% for the bevacizumab biosimilars, a savings of 5.1% (−€11,558,268 [$12,394,104]) was estimated. Due to the increase in the market share of bevacizumab biosimilars compared with the original, it was estimated that in years 2 and 3 the budgetary impact would include decreases of 8.5% (−€29,126,373 [$31,232,647]) and 13.6% (−€52,361,778 [$56,148,320]), respectively, in the pharmaceutical costs derived from the treatment of oncological patients with bevacizumab,” said the researchers.

Consequently, the savings are because of the difference in price between original bevacizumab and its biosimilars, to the market access policies for biosimilars, and the confidence of clinicians in their implementation in the hospital setting where demand is greatest.

Even for indications with a lower cost difference between the scenarios, such as mCRC, biosimilars can save €4900 ($5,254) per patient-year, that converts into a decrease in the pharmacological budget because of the large number of patients who can benefit from biosimilar use.

Finally, the absence of certain data in the literature needed for estimating populations who are candidates for treatment with bevacizumab were missing, but the assumptions were validated by participating experts.

“In conclusion, the inclusion of bevacizumab biosimilars in the Spanish healthcare system will lead to a decrease in budget allocations for the acquisition of biological medicines that will be notable after the first year,” said the researchers.

et al. Budget impact analysis of bevacizumab biosimilars for cancer treatment in adult patients in Spain. 

2023;30(e1):e40-e47. doi:10.1136/ejhpharm-2021-002955

If biosimilars are introduced to Spain, they will most likely save money in the pharmacological budget, according to a budget impact analysis model.

Spain Could Save Millions With Greater Bevacizumab Biosimilar Adoption

On this episode, we’re going to be recapping some of the biggest stories in the immunology space regarding biosimilars, including a new European approval, ustekinumab biosimilar delays, and more.

FDA Approves Celltrion’s Yuflyma, the Ninth Adalimumab Biosimilar

Celltrion Launches Biobetter in Brazil, Shares Phase 3 Plan for MS Biosimilar

Amgen’s Stelara Biosimilar Delayed Until 2025 After Settling With J&J

Dr Colby Evans: The Managed Care Perspective on Biosimilars in Immunology

Dr Vibeke Strand: The Current State of Immunology Biosimilars and the Promise of Future Savings

Samsung Bioepis Report Correlates Biosimilar Pricing Changes With Market Adoption

Biosimilars Business News Recap: A New Partnership; Celltrion Wins Tenders

Tocilizumab Biosimilar LZM008 Demonstrates PK Equivalence in Healthy Participants

RWE: Rituximab Biosimilar GP2013 Effective in Patients With RA After Switching From Originator

Podcasts

On this episode of Not So Different, we recap some of the biggest stories in the immunology space regarding biosimilars, including a new European approval, ustekinumab biosimilar delays, and more.

Biosimilars Immunology Roundup for May 2023—Podcast Edition

Here are the top 5 biosimilar articles for the week of May 29th, 2023.

Number 5: A group of panelists at Asembia 2023 

 that pharmacists, payers, and providers can play in growing biosimilar acceptance and championing policy changes that boost biosimilar utilization.

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

 than that of generics but the market share of biosimilars has grown over time, according to the authors of a study on biosimilar use in the European Union.

 that the FDA has approved Yuflyma (adalimumab-aaty) as the ninth biosimilar referencing Humira (adalimumab).

Here are the top 5 biosimilar articles for the week of May 29, 2023.