Skylar Jeremias

The European Union approves a tocilizumab biosimilar and the US sees another launch, Genentech’s ophthalmology biobetter returns to the market, and Samsung Bioepis shares data on switching to its denosumab biosimilar.

Biogen announced that the European Commission (EC) has 

 Tofidence, a tocilizumab biosimilar monoclonal antibody referencing Roactemra (Actemra in the US). Tofidence’s intravenous formulation has been authorized for treating moderate to severe active rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis, and COVID-19. The EC approval was based on extensive analytical, nonclinical, and clinical data demonstrating Tofidence’s comparability with the reference biologic. Studies confirmed its similar pharmacokinetics, safety, and immunogenicity. Biogen has exclusive commercialization and marketing rights to Tofidence outside of China as part of a partnership with Bio-Thera Solutions, which serves as the product’s developer and manufacturer.

Tyenne Launch and the Market Return of a Biobetter

 of the subcutaneous version of Tyenne (tocilizumab-aazg), the first tocilizumab biosimilar with both intravenous and subcutaneous formulations approved by the FDA. The new formulation, available in a prefilled syringe and autoinjector, offers increased access and affordability for US patients with chronic autoimmune diseases. Tyenne is Fresenius Kabi's third biosimilar in the US and second in its immunology portfolio. The biosimilar, 

 by the FDA in March 2024 and launched as an 

 in April 2024, has shown similar safety and tolerability to the reference product in trials.

 Susvimo, an intravitreal use via an ocular implant utilizing reference ranibizumab (Lucentis) for treating wet age-related macular degeneration (AMD) in the US. This follows the end of a 

 and FDA approval of a post-approval supplement to the biologics license application, which includes updates to the ocular implant and refill needle. Genentech recalled Susvimo in 2022 due to performance issues but has since updated the implant and needle, ensuring they meet performance standards and improving the manufacturing process.

The implant, approved by the FDA in 2021, is surgically inserted during an outpatient procedure and refilled every 6 months. The product is also a biobetter, which is a class of follow-on biologic products that are intentionally altered to improve clinical effects, allow for more time in between doses, or enhance tolerability.

 from a phase 3 study on SB16, a proposed biosimilar to Prolia/Xgeva (denosumab), at the 2024 European Calcified Tissue Society Congress. The randomized, double-blind study showed that SB16 and reference denosumab remained comparable in efficacy, pharmacokinetics, pharmacodynamics, safety, and immunogenicity up to month 18, including during a switching period.

Patients with postmenopausal osteoporosis were initially randomized to receive either SB16 (SB16+SB16) or reference denosumab (DEN+DEN). Patients taking the reference agent were re-randomized at month 12 to continue their treatment or switch to the biosimilar (DEN+SB16).

The follow-up demonstrated that switching to SB16 from reference denosumab was comparable up to month 18. The mean percent change from baseline in lumbar spine bone mineral density (BMD) at month 18 was similar between treatment groups. The least squares mean (LSM) of percent change from baseline in lumbar spine BMD at month 18 was 6.77% (standard error, 0.286) for SB16+SB16. The LSM difference in lumbar spine BMD change for the full analysis set was –0.03% (90% CI, –0.85 to 0.79) between SB16+SB16 and DEN+DEN, and –0.52% (90% CI, –1.48 to 0.43) between the DEN+SB16 and DEN+DEN groups.

Articles

Eye on Pharma: EU Biosimilar Approval, Launches and Product Returns, Denosumab Switching Data

Trastuzumab-dkst was found to be an effective and safe treatment option as adjuvant therapy in HER2-positive (HER2+) 

, with comparable clinical outcomes to the reference product (Herceptin), according to a Brazilian study 

Female breast cancer has consistently been a major health concern, as evidenced by its status as the most commonly diagnosed cancer worldwide in 2020, with 2.3 million new cases | Image credit: Romolo Tavani - stock.adobe.com

Female breast cancer has consistently been a major health concern, as evidenced by its status as the most commonly diagnosed cancer worldwide in 2020, with 2.3 million new cases. In Brazil, it is anticipated that 73,610 new breast cancer cases will occur annually between 2023 and 2025, corresponding to an adjusted incidence rate of 41.89 cases per 100,000 women.

 Data from 14 population-based registries in Brazil showed a stable breast cancer incidence from 2000 to 2010.

Trastuzumab improves survival in HER2+ breast cancer but can be very costly. The present multicentric, observational, prospective real-world study assessed the biosimilar trastuzumab-dkst in 59 Brazilian patients with early-stage HER2+ breast cancer.

“While randomized clinical trials play a crucial role, they often have limitations, such as strict eligibility criteria and potential underestimation of real-world issues such as compliance and tolerability. As a result, the effectiveness of a treatment in clinical practice may differ from trial expectations. Real-world evidence studies are thus increasingly important in oncology, offering insights into the long-term safety and effectiveness of treatments in broader patient populations,” the authors explained.

), female participants aged 18 or older were included; those with cardiac dysfunction or improper use of trastuzumab-dkst were excluded. Data on demographics, medical history, and treatment were collected, with effectiveness assessed via invasive disease-free survival (IDFS) and overall survival (OS). Safety was evaluated using the Eastern Cooperative Oncology Group (ECOG) performance scale and monitoring adverse events (AEs) and left ventricular ejection fraction (LVEF). Partial results from participants who completed treatment by February 2022 across 11 institutions were included.

Of 176 enrolled patients, data from the first 59 who met inclusion criteria and completed treatment with trastuzumab-dkst by February 2022 were presented. These participants (mean [SD] age, 51.7 [12.9] years) represented the initial cohort of an ongoing study. All patients underwent surgery, with 67.8% having conservative breast surgery and 32.2% undergoing mastectomy. The mean time from diagnosis to the first adjuvant treatment with trastuzumab-dkst was 5.5 months. The median age at diagnosis was 50 (range, 29-83) years, with 98.3% having invasive ductal breast cancer and 84.7% showing a HER2 score of 3 or higher in immunohistochemistry tests.

Most participants (74.6%) received adjuvant treatment with trastuzumab-dkst, 18.6% received it with pertuzumab, and 3.4% switched from reference trastuzumab to trastuzumab-dkst. The average duration of anti-HER2 therapy was 10.2 months, covering around 14 cycles of 21 days each. The shorter duration than the recommended 12 months was due to prior neoadjuvant therapy. Overall, 61% of patients received adjuvant chemotherapy, with most (77.8%) treated with taxane, and 62.7% of participants used adjuvant endocrine therapy for an average of 7.8 months.

The median follow-up was 31.7 months, with 59% of patients reaching at least 30 months. The IDFS rate was 94.5% at 24 and 31.7 months. Only 3 patients had disease recurrence, all with distant metastasis. The OS rate was 100%, so the median OS was not reached.

On trastuzumab-dkst administration days, 63.8% of patients were fully active, 34.0% had restricted activity, and 1 was unable to work but could self-care. Regarding safety, 78.0% experienced AEs, mostly during monotherapy (67.8%). Four serious AEs were noted, with 2 during and 2 after treatment. Two patients had infusion reactions. LVEF reductions of at least 10% occurred in 16.9%, but none fell below 50%. Two had reduced doses, and there were no treatment interruptions.

The authors concluded, “Our study bolsters the existing pivotal data concerning the biosimilar trastuzumab-dkst, underscoring its real-world efficacy and safety in the adjuvant treatment of early HER2-positive [breast cancer]. The comprehensive long-term efficacy and safety data we provide further establish trastuzumab-dkst as a cost-saving alternative in oncological care. These findings carry important implications for enhancing patient access to essential therapies and optimizing the efficiency of health care resource utilization.”

1. Gagliato D, Reinert T, Rocha C, et al. Real-World Study of Adjuvant Biosimilar Trastuzumab-dkst for HER2-Positive Breast Cancer Treatment in a Brazilian Population. 

. Published online June 5, 2024. doi:10.1007/s40487-024-00284-5

2. Lemos LLP, Souza MC, Guerra AAG, Piazza T, Araújo RM, Cherchiglia ML. Racial disparities in breast cancer survival after treatment initiation in Brazil: a nationwide cohort study. 

. 2024;12(2):E292-E305. doi:10.1016/S2214-109X(23)00521-1

A Brazilian real-world study found trastuzumab-dkst to be an effective and safe adjuvant therapy for HER2-positive (HER2+) breast cancer, with clinical outcomes comparable to reference trastuzumab.

Trastuzumab-dkst Shows Promising Results in Real-World Setting for HER2+ Breast Cancer

On this episode of Not So Different, we review biosimilar news coming out of June, with clinical trial results from conferences and a study showcasing how to overcome economic and noneconomic barriers to oncology biosimilars.

Biosimilars Check-In: Application Acceptances, European Approvals, New Partnerships

Overcoming Economic, Noneconomic Barriers to Biosimilar Adoption in Oncology

EHA 2024: Rituximab Biosimilars Improve Quality of Life, Infusion-Related Reactions

New Data Show Safety of Ado-Trastuzumab, Trastuzumab Biosimilars in HER2+ Cancers

ASCO Posters Reflect on Reimbursement Trends, Combination Therapies Involving Biosimilars

ASCO 2024 Posters Showcase Positive Data on Denosumab, Pegfilgrastim Biosimilars

Authors Spotlight Long-Term Solutions to Ensure Biosimilar Market Sustainability

Part 2: Unlocking the Potential of Biosimilars to Improve Health Equity

Podcasts

Biosimilars Oncology Roundup for June 2024—Podcast Edition

As Celltrion publishes phase 3 data on its tocilizumab biosimilar, other companies finalize partnerships, and Formycon begins development for a pembrolizumab biosimilar.

Phase 3 Data on Celltrion’s Tocilizumab Biosimilar

At the annual European Congress of Rheumatology (EULAR) 2024, Celltrion presented positive phase 3 data for CT-P47, a biosimilar candidate referencing Actemra (tocilizumab), in patients with moderate to severe rheumatoid arthritis (RA).

The study involved 471 patients who were randomized to receive either 8-mg doses of CT-P47 or reference tocilizumab every 4 weeks for 20 weeks. At week 24, patients on the reference product were rerandomized to continue with it or switch to CT-P47 until week 48.

The primary end point was the improvement in disease activity score 28 erythrocyte segmentation rate at weeks 12 and 24. The results showed equivalent efficacy between the 2 groups, with estimated score differences of –0.01 (95% CI, –0.26 to 0.24) at week 12 and –0.1 (95% CI, –0.30 to 0.10) at week 24, within the pre-defined equivalence margins. The treatment groups had similar mean serum concentration, incidence of treatment-emergent adverse events, and antidrug antibody positivity, demonstrating comparable pharmacokinetics, safety, and immunogenicity.

Additionally, a phase 1/3 study compared the pharmacokinetic (PK) similarity between the CT-P47 autoinjector (AI) and the pre-filled syringe (PFS) in healthy subjects, showing higher usability and similar PK profiles for the AI in patients with RA. No new safety signals were identified.

“The availability of tocilizumab biosimilars…represents a great opportunity to reduce treatment costs, contributing to health-care budget sustainability, improved patient access, and lower disease burden,” said Taehun Ha, vice president and Europe Division head at Celltrion.

Two new partnerships in the biosimilar space were finalized. Alvotech and STADA Arzneimittel have chosen to expand their current partnership to include the development and commercialization of AVT03 (Uzpruvo), a denosumab biosimilar candidate.

 The deal originally covered an adalimumab biosimilar and an ustekinumab biosimilar.

Under the agreement, Alvotech will develop and manufacture AVT03 in Reykjavik, while STADA will hold marketing authorization and have semi-exclusive commercial rights in Europe and exclusive rights in selected Central Asian and Middle Eastern countries. Additionally, STADA’s rights to the adalimumab and ustekinumab biosimilars will extend to Commonwealth of Independent States countries in Central Asia. Alvotech will regain commercial rights to AVT06, an aflibercept biosimilar.

Anil Okay, chief commercial officer of Alvotech, remarked, “We look forward to continuing to work with STADA on increasing patient availability of more affordable biologics in the denosumab market, as we have already done with our citrate-free, high-concentration biosimilar to Humira [reference adalimumab].”

STADA also formed a partnership with Bio-Thera Solutions regarding a golimumab biosimilar (BAT2506) candidate for the European Union (EU) and UK.

Bio-Thera Solutions will develop, manufacture, and supply BAT2506, while STADA will have exclusive commercialization rights in the EU, UK, Switzerland, and selected countries. Bio-Thera will receive a $10 million upfront payment and up to $147.5 million in milestone payments.

Bryan Kim, head of global specialty at STADA commented, “With global sales in 2023 of US$2.2 billion, including more than US$1 billion outside of the US, golimumab represents a compelling opportunity to broaden patient access to biological treatments and build scale in immunology alongside our approved adalimumab and ustekinumab biosimilars.”

Formycon Initiates Clinical Development of for Pembrolizumab Biosimilar

Formycon announced the start of the clinical development program for FYB206, a biosimilar for Keytruda (pembrolizumab), with the inclusion of the first patient.

Pembrolizumab is a monoclonal antibody used to treat various tumors by blocking the PD-1/PD-L1 interaction, activating the body's antitumor immune response. Sales for Keytruda—the world's best-selling drug, with $25 billion in sales in 2023—are expected to grow due to rising cancer diagnoses.

The phase 1 study to compare the pharmacokinetics, safety, and tolerability of FYB206 with the reference product in patients with melanoma, designed in collaboration with the FDA and European Medicines Agency. A parallel Phase III study will compare FYB206's safety and efficacy with Keytruda in patients with non-small cell lung cancer. The company said it anticipates the earliest market entry for FYB206 after Keytruda's market exclusivity expires in 2029 for the US and 2030 for the EU.

“We are at the forefront of the development of a pembrolizumab biosimilar. Our FYB206 project not only has immense commercial potential, but above all offers exceptional therapeutic options. We are doing absolutely everything we can to ensure that more cancer patients worldwide can be treated with this drug in the future. After all, only biosimilars combine quality and efficacy with cost efficiency and thus improve healthcare,” emphasized Stefan Glombitza, PhD, CEO of Formycon.

1. Celltrion showcases promising results in phase III study for CT-P47, a biosimilar candidate of RoActemra

(tocilizumab) in patients with rheumatoid arthritis (RA) at EULAR 2024. News release. Celltrion; June 14, 2024. Accessed June 26, 2024. 

https://www.celltrion.com/en-us/company/media-center/press-release/3264 

2. Alvotech and STADA add to strategic alliance through denosumab partnership. News release. Alvotech; June 11, 2024. Accessed June 26, 2024. 

https://investors.alvotech.com/news-releases/news-release-details/alvotech-and-stada-add-strategic-alliance-through-denosumab/

3. Bio-Thera and STADA reach exclusive agreement for BAT2506, a proposed golimumab biosimilar, in the EU and UK. News release. Bio-Thera Solutions; May 28, 2024. Accessed June 26, 2024. 

https://www.prnewswire.com/news-releases/bio-thera-and-stada-reach-exclusive-agreement-for-bat2506-a-proposed-golimumab-biosimilar-in-the-eu-and-uk-302156882.html

4. Formycon starts clinical development program for FYB206,
a biosimilar candidate for immuno-oncology blockbuster drug Keytruda

. News release. Formycon; June 13, 2024. Accessed June 26, 2024. 

https://www.formycon.com/en/blog/press-release/formycon-starts-clinical-development-program-for-fyb206-a-biosimilar-candidate-for-immuno-oncology-blockbuster-drug-keytruda/

Eye on Pharma: New Data, Clinical Developments, and Biosimilar Partnerships

As the weather heats up for the US and Europe, so too did the biosimilar news coming out of June, with clinical trial results from conferences and a study showcasing how to overcome economic and noneconomic barriers to oncology biosimilars.

Clinical trial results from conferences and a study showcases how to overcome economic and noneconomic barriers to oncology biosimilars rounded out this month's biosimilar news.

Some news came out of Europe and the US, with the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMA) adopting a 

 on Avzivi, a bevacizumab biosimilar for multiple cancers.

Additionally the FDA and the EMA have accepted applications for denosumab biosimilars, which can be used in patients with bone loss due to prostate or breast cancer. The FDA's acceptance concerned Fresenius Kabi's candidate, and the EMA's involved a product being developed by Shanghai Henlius Biotech and Organon.

 outlined the challenges and solutions for increasing biosimilar adoption in oncology. It highlighted economic barriers such as reimbursement policies and pricing dynamics, as well as noneconomic barriers like provider and patient awareness. Strategies to overcome these included improving education on biosimilars, adjusting reimbursement policies to favor biosimilars, and enhancing collaboration among stakeholders. These efforts aimed to achieve cost savings and improve patient outcomes in oncology through increased biosimilar use.

Several posters came out of the 2024 annual meetings of the European Hematology Association (EHA) and the American Society of Clinical Oncology (ASCO).

Two studies presented at EHA 2024 evaluated the 

 on patients with lymphatic cancers. The first study focused on quality of life (QOL) in patients with non-Hodgkin lymphoma and chronic lymphocytic leukemia (CLL), finding that while QOL was generally acceptable, functional well-being was most compromised. The second study assessed infusion-related reactions (IRRs) from rituximab biosimilars in patients with chronic lymphoproliferative disorders, finding comparable IRR rates to existing data, with specific conditions like diffuse large B-cell lymphoma and CLL showing different IRR frequencies.

At ASCO 2024, posters highlighted the safety and efficacy of 

trastuzumab and ado-trastuzumab biosimilars

 in HER2-positive cancers. A phase 2 study with 40 patients showed that combining trastuzumab biosimilar Herzuma with neratinib yielded a 23.1% objective response rate and manageable adverse events, particularly diarrhea. Another study on a biosimilar of ado-trastuzumab emtansine in 116 patients demonstrated similar efficacy and safety to the reference product, increasing accessibility for patients in low- and middle-income countries.

 analyzed Medicare reimbursement trends for biologics and biosimilars, and a pegfilgrastim biosimilar combined therapy in advanced hepatocellular carcinoma (HCC). The first study revealed that biosimilars reduced health care costs and drug reimbursement rates compared with reference agents. The second study demonstrated that combining SCT-I10A (anti-PD-1 monoclonal antibody) and SCT510 (bevacizumab biosimilar) improved overall survival and progression-free survival in patients with HCC compared with sorafenib, with an acceptable safety profile.

 highlighted the positive safety and efficacy data for denosumab and pegfilgrastim biosimilars. A denosumab biosimilar candidate (FKS518) showed therapeutic equivalence and similar safety to the originator in postmenopausal osteoporosis, with significant increases in bone mineral density. A systematic review and meta-analysis confirmed that pegfilgrastim biosimilars were effective in reducing the duration of severe neutropenia in patients receiving cytotoxic chemotherapy, with comparable safety profiles to the originator. Both studies emphasized the potential of biosimilars to improve patient access and reduce treatment costs.

Market Analyses With Oncology Implications

factors undermining biosimilar market sustainability

 and recommended long-term solutions. It highlighted how pricing and procurement practices led to rapid price erosions, affecting development and marketing costs. The authors emphasized the need for multistakeholder-supported principles based on collective action theory to create sustainable policies. They suggested cooperative strategies, incentive systems, and coordination across governance levels to reconcile competing interests and achieve long-term market sustainability. The commentary called for further research and stakeholder agreement for effective implementation.

Lastly, in the second part of the series on 

, attention shifted to the obstacles hindering affordable biosimilar treatments, particularly among underserved communities. Key barriers highlighted include the influence of payers, pharmacy benefit managers (PBMs), and financial incentives that favor more expensive originator biologics over biosimilars. These incentives, managed by managed care organizations and PBMs, often lead to higher profits when originator biologics are prescribed, thus limiting the adoption and potential cost savings of biosimilars. Addressing these systemic issues through policy changes, enhanced education, and improved transparency among stakeholders is crucial to achieving equitable access to biosimilar therapies.

Biosimilars Oncology Roundup: June 2024

Formycon and its licensing partner Klinge Biopharma announced the 

 for Ahzantive (aflibercept-mrbb), making it the third approval for a biosimilar referencing Eylea (aflibercept).

The approval follows those for Biocon Biologics's Yesafili (aflibercept-jbvf) and Samsung Bioepis' Opuviz (aflibercept-yszy), which were approved in 

. Aflibercept products are administered intravitreally and inhibit vascular endothelial growth factor, which causes excessive blood vessel formation in the retina.

Ahzantive has received FDA approval for treating patients with age-related neovascular (wet) macular degeneration (nAMD) and other serious retinal diseases, including diabetic macular edema, diabetic retinopathy, and macular edema following retinal vein occlusion.

“The FDA approval of FYB203/Ahzantive is another key milestone on our way to becoming the leading pure-play biosimilar developer. It highlights the expertise and experience of our team. With the Eylea® biosimilar FYB203/Ahzantive and our already approved Lucentis biosimilar FYB201, we have achieved an outstanding position in ophthalmic biosimilar therapies. We are thus improving healthcare for patients with retinal diseases by offering effective, safe and, above all, affordable treatment options,” commented Stefan Glombitza, PhD, CEO of Formycon.

Additionally, a marketing authorization application for Ahzantive was submitted to the European Medicines Agency (EMA) at the end of 2023. A decision from the EMA is anticipated by early 2025.

The FDA’s decision was based on a comprehensive data package including research comparing the safety, efficacy, and tolerability of Ahzantive (FYB203) with that of Eylea in patients with nAMD. Formycon published that the MAGELLAN-AMD phase 3 randomized, double-blind, multicenter analysis (

) met its primary end points demonstrating comparable efficacy between FYB203 and Eylea.

In the study, participants with nAMD aged 50 and older were randomized 1:1 to receive the biosimilar or reference product every 4 weeks for the first 3 consecutive doses, followed by 1 intravitreal injection every 8 weeks through study completion. Results showed that the 2 products had comparable biosimilarity and no new safety signals were identified.

AMD is the leading cause of visual impairment and blindness in Europe, and its prevalence is expected to rise, necessitating updated data for health care planning. A systematic review and meta-analysis of studies since 1996 estimated that 25.3% of individuals 60 years and older have early or intermediate AMD, and 2.4% have late AMD.

The annual incidence of late AMD is 1.4 per 1000 individuals. By 2050, the number of people with AMD in the European Union is expected to increase from 67 million to 77 million, with late AMD cases rising from 400,000 to 700,000 per year. This growing burden highlights the need for additional health care resources and planning.

1. Formycon receives FDA approval for FYB203/Ahzantive®) (aflibercept-mrbb), a biosimilar to Eylea®). News release. Formycon. July 1, 2024. Accessed July 1, 2024. 

https://www.formycon.com/en/blog/press-release/formycon-receives-fda-approval-for-fyb203-ahzantive/

2. Li JQ, Welchowski T, Schmid M, et al. Prevalence and incidence of age-related macular degeneration in Europe: a systematic review and meta-analysis. 

. 2020;104:1077-1084. doi:10.1136/bjophthalmol-2019-314422

The FDA has approved Ahzantive (aflibercept-mrbb) as the third biosimilar referencing Eylea (aflibercept) for the treatment of eye conditions, including age-related macular degeneration.

Ahzantive Receives FDA Approval as New Eylea Biosimilar

 Samsung Bioepis’ Pyzchiva (ustekinumab-ttwe) for the treatment of inflammatory conditions, including plaque psoriasis and ulcerative colitis.

The approval of Pyzchiva marks the third ustekinumab approval for the US as well as the 14th interchangeable biosimilar. | Image credit: Argus - stock.adobe.com

Pyzchiva marks the third biosimilar referencing Stelara (ustekinumab) to be approved for the American market, and the biosimilar was approved with an interchangeability designation, allowing for it to be substituted for the reference product at the pharmacy level without waiting for physician approval.

Upon launch, Pyzchiva will be available with intravenous and subcutaneous administration options. Here is the full list of patient indications:

Moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy

Moderately to severely active Crohn disease

Moderately to severely active ulcerative colitis

“The FDA approval of Pyzchiva as a biosimilar to Stelara is an important milestone for patients living with inflammatory conditions, as biosimilars can offer more choice and access to biologic treatments,” said Byoung In Jung, vice president and regulatory affairs team leader at Samsung Bioepis. “In addition, biosimilars have a potential to reduce the financial burden of health care systems, especially in the US where biologics account for more than 46% of the annual drug spending. We will continue to reinforce our commitment to widen access to medicines by advancing our biosimilar pipeline for the benefits of patients, health care providers, and health care systems around the world.”

 (ustekinumab-auub) in November 2023 and 

 (ustekinumab-aekn) in April 2024. Wezlana was developed by Amgen and Selarsdi was developed by Alvotech and will be marketed in the US by Teva Pharmaceuticals as part of a commercialization partnership.

The FDA approved Pyzchiva based on comprehensive evidence, including analytical, nonclinical, and clinical data, confirming its biosimilarity to Stelara with no significant differences in safety, purity, or potency. A phase 1 study (

) showed equivalent pharmacokinetics, safety, tolerability, and immunogenicity between Pyzchiva (SB17) and Stelara in healthy volunteers. A phase 3 study (

) in patients with moderate to severe plaque psoriasis demonstrated similar efficacy, safety, and pharmacokinetics for SB17 and Stelara up to week 28. These findings were published in the 

Journal of the American Academy of Dermatology

2024 American Academy of Dermatology annual meeting

Pyzchiva, developed by Samsung Bioepis, will be commercialized by Sandoz in the US as part of a September 2023 commercialization agreement between the companies. Sandoz will have exclusive commercialization rights to Pyschiva in the US, Canada, European Economic Area, Switzerland, and the UK.

In the US, the license period for Pyzchiva will commence on February 22, 2025, as per the 

 between Samsung Bioepis and Janssen Biotech, the maker of Stelara. Similar settlement agreements have resulted in delayed launches for Wezlana and Selarsdi from 2024 to 2025.

Samsung Bioepis has a portfolio of 11 biosimilars spanning immunology, oncology, ophthalmology, hematology, nephrology, and endocrinology. As of June 2024, 7 of these biosimilars are approved in the US, with 4 already commercially available.

FDA approves Pyzchiva (ustekinumab-ttwe), Samsung Bioepis’ biosimilar to Stelara. News release. Samsung Bioepis. July 1, 2024. Accessed July 1, 2024. https://www.biospace.com/article/releases/fda-approves-pyzchiva-ustekinumab-ttwe-samsung-bioepis-biosimilar-to-stelara/

Pyzchiva (ustekinumab-ttwe) is the third ustekinumab biosimilar to receive approval for the American market. It was also approved with interchangeability.

FDA Approves Samsung Bioepis’ Pyzchiva, a Biosimilar to Stelara

European Hematology Association’s annual meeting (EHA 2024)

 evaluated how rituximab biosimilars impact quality of life

 and infusion-related reactions (IRR) in patients with lymphatic cancers.

EHA 2024 took place in Madrid, Spain from June 13 to 16, 2024. | Image credit: Anusorn - stock.adobe.com

, the researchers looked at how quality of life was informed by biosimilar rituximab therapy.

The treatment of hematologic malignancies has led to significant advancements in survival rates and patient outcomes. However, the impact of these treatments on the quality of life (QOL) of patients remains a critical concern. QOL encompasses a wide range of patient experiences, including physical, functional, emotional, and social well-being. In hematologic malignancies, the disease and its treatment can profoundly affect various aspects of a patient's life.

According to the authors, the QOL measure is crucial for understanding the challenges faced by individuals with hematologic diseases, emphasizing the need for patient-centered care strategies to improve overall support and outcomes.

The primary aim of this study was to investigate the QOL of patients undergoing treatment for hematologic malignancies and uncover critical areas where interventions are needed to improve overall QOL. The multicenter study was conducted across 13 onco-hematology units in eight Italian regions, focusing on adults diagnosed with non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) who received rituximab treatment between March 2018 and June 2022. Patient-reported data were collected using the FACT-Lym questionnaire at the third drug infusion to assess Health-Related Quality of Life (HRQOL) across various domains in individuals with B-cell malignancies.

Researchers included 430 participants (n = 249 male; most were aged 65-75 years). The majority of participants were diagnosed with NHL (90%), followed by CLL (6.3%) and other hematological diseases (3.72%).

The findings suggested that although participants generally report an acceptable QOL across multiple dimensions, functional well-being is the most compromised aspect. Emotional, social, and physical well-being are less adversely affected on average. The researchers noted that pattern indicates the nuanced impact of treatment on different life areas, highlighting the importance of addressing specific domains to enhance overall patient care.

Participants with NHL and CLL reported similar QOL scores, with those with CLL faring slightly better in physical and lymphoma-specific well-being. Individuals with other hematological conditions generally reported lower scores in several domains, indicating a need for targeted interventions to address their QOL.

 found that the rate of IRRs as a result of treating patients with chronic lymphoproliferative disorders (cLPDs) with rituximab biosimilars was comparable with previously published data, with no observed differences between the 2 biosimilars studied.

A study was conducted to assess the frequency and severity of IRRs associated with the rituximab biosimilars Rixathon and Blitzima in patients with a cLPD treated at the Clinic for Hematology, University Clinical Center of Serbia from 2020 to 2022. Medical records of 200 patients were analyzed to identify associations between IRR occurrence and various clinical, radiographic, and therapeutic features, and to compare IRR frequencies between different cLPD entities and the 2 rituximab biosimilars. All patients received premedication with methylprednisolone, paracetamol, and loratadine.

IRRs occurred in 71% of patients, particularly during their first infusion. The authors said that a small percentage of patients may need to discontinue rituximab due to serious IRRs, and they observed a low incidence of fatal outcomes (0.07%).

The occurrence of IRRs was not dependent on gender, age, clinical stage, disease localization (extranodal vs nodal), presence of “B” symptoms, bulky mass, Eastern Cooperative Oncology Group performance status, type of adjunct chemotherapy, or the timing of rituximab administration (first cycle vs second cycle and onward).

Patients with diffuse large B-cell lymphoma (DLBCL) exhibited significantly fewer IRRs compared with those with CLL (15% vs 34%; 

 = .045). Additionally, patients treated in second or later therapeutic lines experienced more IRRs compared with those in the first treatment line (

 = .0233). Factors such as arterial hypertension (AH), type 2 diabetes (T2D), coronary artery disease, and smoking did not influence IRR occurrence.

In the subgroup of patients with DLBCL (n = 67), those with AH experienced IRRs more frequently (

= .014). Among patients with CLL (n = 76), those with AH and T2D showed a higher frequency of IRRs (

1. Masnata LJ, Urru S, Alegiani SS, Mayer F, Campomori A. Quality of life (QOL) in patients with hematologic malignancies receiving rituximab biosimilars: results from a real-world setting. Presented at EHA 2024; June 13-16, 2024; Madrid, Spain. Abstract P1689. 

https://s3.eu-central-1.amazonaws.com/m-anage.com.storage.eha/temp/eha24_abstract_bodies/P1689.pdf

2. Vukovic V, Karan-Đurašević T, Pesic A, et al. Infusion-related reactions in patients with chronic lymphoproliferative disorders treated with two rituximab biosimilars: single center experience. Presented at EHA 2024; June 13-16, 2024; Madrid, Spain. Abstract PB3059. 

https://s3.eu-central-1.amazonaws.com/m-anage.com.storage.eha/temp/eha24_abstract_bodies/PB3059.pdf

Two posters presented at the European Hematology Association’s annual meeting (EHA 2024) evaluated how rituximab biosimilars impact quality of life and infusion-related reactions in patients with lymphatic cancers.

Key findings showed that there continues to be a lack of understanding and/or confidence in biosimilars among providers and patients, leading to diminished provider willingness to prescribe biosimilars and patient perceptions about the safety of switching to a biosimilar.

, aimed to describe the opinions of patients undergoing treatment with originator biologics and medical consultants managing their conditions and identify barriers and enablers to switching to a biosimilar.

Spending on biologics and biosimilars in the UK rose from £6.63 billion in 2017 to £9.45 billion in 2023, with biosimilars helping to control costs. | Image credit: millaf - stock.adobe.com

“The patient needs to be assured that the process is not just a cost-saving exercise but will allow additional services to be provided across the NHS [National Health Service] to patients, that the treatments are equivalent to their biologics, effective, and equally safe as adverse drug reactions were a concern for the patients, and that an option to revert back would be available to them,” wrote the authors.

Biologics target specific immune proteins to reduce inflammation but are expensive and often used after other treatments fail. Biosimilars entered the UK market beginning in 2006, allowing earlier treatment and expanded access. Unlike generic drugs, biosimilars are not identical to their reference biologics, which has caused concerns about the safety of switching to biosimilars among providers and patients.

In November 2022, the UK’s Medicines and Healthcare products Regulatory Agency updated its guidance on licensing biosimilar products, stating that authorized biosimilars are interchangeable with their reference products and other biosimilars to the same reference product.

 This means prescribers can expect the same therapeutic effect when switching between them, making such switches standard clinical practice. However, switching safety concerns persist.

Despite evidence of their safety and effectiveness, gaps in prescriber knowledge and patient doubts hinder biosimilar adoption. Spending on biologics and biosimilars in the UK rose from £6.63 billion ($8.4 billion) in 2017 to £9.45 billion ($11.9 billion) in 2023, with biosimilars helping to control costs. The authors stressed that effective communication from health care providers will be crucial to address concerns and prevent patients from experiencing negative outcomes after switching to biosimilars caused by the nocebo effect. Studies have also emphasized the need for through education to ensure successful transitions to biosimilars and maximize cost savings.

This study explored views on switching from originator biologics to biosimilars using focus groups and interviews. Nine patients and 5 consultants took part in the analysis. Patients on infliximab (n = 2) or etanercept (n = 7) were randomly selected for focus groups, while medical consultants were individually interviewed. The primary researcher, a registered pharmacist, conducted the study. Patients had to be on their medication for at least 6 months. An 80% response rate was achieved, but many participants couldn't attend initially, prompting a second round of invitations. Consultants were invited via email for 45-minute interviews. Both focus groups and interviews were recorded and transcribed.

The focus groups included a presentation on biologics and biosimilars to ensure consistent knowledge. Discussions covered the impact of switching, communication methods, and necessary patient information. Data were anonymized and analyzed to identify themes.

Five consultants from gastroenterology, dermatology, and rheumatology participated in face-to-face interviews. At the time of the study, none had prescribed biosimilar medicines. Four main themes were identified:

There was consensus among consultants about the financial benefits of switching from biologics to biosimilars. The savings could be redirected within the NHS or used to increase patient access to treatments. One consultant highlighted that lower costs could lower the threshold for prescribing these drugs, allowing more patients to benefit.

Consultants agreed that evidence of biosimilar efficacy and safety was crucial for making the switch. Most trusted the regulatory approvals from bodies like the FDA and European Medicines Agency as sufficient evidence. Concerns about adverse effects were noted, but they were seen as similar to those of reference biologics. One consultant expressed caution, preferring more data before switching. Manufacturer reputation was also important, with some consultants trusting known manufacturers more. There was concern that lower costs might lead to higher adverse event reporting. Despite this, most consultants agreed that monitoring should remain the same as for biologics, with some suggesting more intensive monitoring initially until more robust data was available.

The consultants felt that doctors or specialist nurses should handle the communication about switching to biosimilars, rather than pharmacists, especially if there was no preexisting relationship with the patient. Effective communication might require additional resources, and there was concern about having enough personnel to support the enhanced patient contact required.

Regarding effective communication, results showed a distinction between what patients want to know and how the information should be communicated. Patients need time to process information about switching to biosimilars. They should be given time to review and absorb this information and have the option to revert to the original biologic if they experience issues. This option was seen as important for patient reassurance and acceptance of the switch.

Both written and face-to-face communication were preferred for informing patients about the switch. Simple information sheets and frequently asked question documents were recommended to avoid overwhelming patients with too much information at once. Consultants noted that upfront information could prevent unnecessary anxiety later. Information from hospitals was seen as more trustworthy than from manufacturers. Transparency about the reasons for switching, cost savings, and examples of what the savings could fund were also deemed important. For instance, one consultant suggested explaining that the savings could fund additional treatments or procedures, enhancing patient understanding and acceptance of the switch.

The study had limitations, including no double coding and a small sample size for the infliximab originator focus group. Although it included gastroenterology, rheumatology, and dermatology representations, the lack of time to repeat focus groups and ensure data saturation was a limitation. Further research should focus on equality, diversity, and inclusivity, particularly involving marginalized groups prescribed biosimilars. Socioeconomic and ethnic backgrounds were not captured but were broadly representative of the local population.

1. Rosembert DC, Twigg MJ, Wright DJ. Patient’s and consultant’s views and perceptions on switching from an originator biologic to biosimilar medication: a qualitative study. 

. 2024;12(2):65. doi:10.3390/pharmacy12020065

2. Guidance on the licensing of biosimilar products. MHRA. Updated November 7, 2022. Accessed June 26, 2024. 

https://www.gov.uk/government/publications/guidance-on-the-licensing-of-biosimilar-products/guidance-on-the-licensing-of-biosimilar-products

Lack of knowledge and confidence in biosimilars continues despite growing education efforts, impacting provider willingness to prescribe biosimilar medicines and patient perceptions about their treatment and switching to a biosimilar.

Biosimilar Adoption in the UK: Patient and Consultant Views on Safety and Switching

 critiqued factors found to undermine biosimilar market sustainability and made recommendations for long-term solutions that could improve endangered markets.

Although most stakeholders in the biosimilar space can agree that long-term market sustainability is a major concern, many disagree on the best policy approach to ensure a robust, competitive marketplace. Image credit: TStudious - stock.adobe.com

The development and marketing costs for biosimilars are significantly influenced by pricing and procurement practices that cause rapid price erosions. An 

 highlighted that nearly one-third of high-sales biologics losing exclusivity in the next decade lack biosimilar candidates.

 Additionally, the same report found that the European Union could miss out on a minimum of €15 billion in cost savings from a lack of biosimilars for biologics about to lose exclusivity, which could have implications for overall treatment cost efficiency gains and medication availability.

This, coupled with limited commercial opportunities for many biologics, raises concerns about the long-term viability of biosimilar markets and what is needed to achieve sustainable competition. The purpose of the commentary piece was to raise awareness of vulnerabilities associated with some global biosimilar markets and difficulties with reaching consensus on long-term policy advancements.

When discussing disagreements on how to move sustainability efforts forward, there are 2 perspectives to consider: the supply side and the demand side.

On the supply side, payers and health care managers aim to reduce costs through significant price cuts and biosimilar savings, which can sometimes hurt long-term market competition. Concerns include anticompetitive procurement practices favoring originators and tendering procedures that select a single biosimilar winner. Limited competition may also disrupt biologic supply continuity and patient care, with biosimilar withdrawals and discontinuations potentially exacerbating these issues.

Policymakers have sometimes implemented top-down biosimilar policies to drive early uptake and savings, such as mandated switch protocols, such as 

 Though beneficial short-term, these strategies are often unpopular with health care professionals and patients, who prefer avoiding therapy switches unless there are clear care quality and financial benefits, with some providers calling for more data on the safety of 

In the absence of central strategies, individual health care communities, such as 

 and the American Oncology Network (AON), have successfully implemented their initiatives, but scaling and sustaining these efforts remains challenging without supportive environments.

“It’s imperative for formulary strategies to effectively navigate and overcome the dynamic challenges present in the biosimilar market…. We are all here for biosimilars and we need to come and work together to learn from each other—from the patients, to the payers, to the policy makers, to the providers—to ensure that we have a long-term plan to support our patient,” said Melody Chang, vice president of pharmacy operations at AON, during her presentation on AON’s successes at the 

Disagreements also exist on how to communicate and reallocate biosimilar savings, with some advocating for transparency and local reallocation, while others prefer central health administration control. These conflicts, viewed as "social dilemmas," could be resolved through cooperative strategies that prioritize long-term societal benefits, as suggested by collective action theory.

Principles for managing local-scale Commons, initially applied to natural resources, are now being tested for broader applications, including health care. Despite challenges, this research is increasingly used in diverse domains like digital and space governance. Few examples currently apply collective action theory to health care, but interest is growing. Studies demonstrate applying collective action theory to health care reform.

This commentary suggests that multistakeholder-supported principles, based on collective action theory, can inform comprehensive frameworks for biosimilars. The authors stressed that future policy frameworks should involve multistakeholder panels, adopt long-term visions, design incentive systems aligned with stakeholder needs, evaluate cost-benefit balances, foster coordination across governance levels, define shared goals, and use policy outcome data to adapt frameworks.

Past policies lacking these principles faced implementation challenges, such as ineffective benefit-sharing strategies and compliance issues with top-down mandates. Identifying these principles is a step toward reconciling competing interests for long-term gain, although reforming biosimilar policy frameworks in Europe will be a multiyear process. European policy changes may influence global biosimilar markets, promoting sustainable practices.

Authors of a commentary piece propose solutions to sustainability issues for biosimilar markets and shed light on common sustainability challenges global markets face.