Cameron Santoro is an associate editor for The Center for Biosimilars

Cameron Santoro

The Top 5 Biosimilar Articles for the Week of April 14

: Early market entry, manufacturing efficiency, and market share are critical to biosimilar development success, while technical complexity and competition heavily impact returns, according to a study presenting a risk-adjusted 

, pharmaceutical companies accelerated biosimilar expansion through strategic acquisitions and partnerships in hopes of boosting patient access to lower-cost treatments in immunology and oncology.

: Teva and Samsung Bioepis have launched Epysqli, a cost-saving Soliris biosimilar, offering a 30% discount and new hope for patients with rare, life-threatening 

: Lawmakers and expert witnesses emphasized the potential of biosimilars to lower health care costs by overcoming barriers like pharmacy benefit manager practices, limited awareness, and regulatory delays to improve access and competition in chronic disease management 

: Biocon Biologics expands its oncology biosimilar roster after gaining 

 (bevacizumab-nwgd), the sixth biosimilar referencing Avastin (bevacizumab).

To read all of these articles and more, visit 

Videos

Here are the top 5 biosimilar articles for the week of April 14, 2025.

Trastuzumab biosimilars saw significant market uptake in Japan after reimbursement incentives were implemented, but bevacizumab biosimilars did not experience a similar response. | Image Credit: Shevon - stock.adobe.com

Reimbursement incentives significantly increased the market uptake of trastuzumab biosimilars for cancer treatment but failed to produce a similar effect for bevacizumab biosimilars, suggesting policy makers design reimbursement strategies tailored to each biosimilar to optimize effectiveness, according to a time series analysis published in 

Novel cancer drug costs are continuously rising, and health care systems are looking to rely on the entry of biosimilars to lead them to significant cost reductions. Patients receiving cancer treatment in Japan have an estimated annual economic burden of about $12.6 million (¥1296 million), including $11 million (¥1128 million) for targeted therapy, $1.3 million (¥130 million) for nontargeted therapy, and $0.4 million (¥38 million) for anticancer therapy–related costs.

The Japanese government is focusing more on reimbursement incentive policies to promote biosimilar adoption within the health care system.

 The biosimilar adoption incentive policy will offer medical institutions a premium of approximately $10 (¥1500) per prescription for up to 3 months.

Researchers aimed to determine the effectiveness of this policy intervention for oncology drugs, specifically trastuzumab and bevacizumab, in outpatient settings using an interrupted time series analysis. They utilized health insurance claims data from January 1, 2005, to March 31, 2023, for Tokyo, Japan.

Trastuzumab insurance claims (22,440) for treating breast or gastric cancer and bevacizumab claims (14,022) for treating colorectal or lung cancer were utliized for this analysis. There were 11,622 claims in the preintervention period for trastuzumab (April 2021-March 2022) and 10,818 in the postintervention period (April 2022-March 2023). Bevacizumab had 6973 claims prior to intervention and 7049 afterward.

For trastuzumab, 97% of the claims were from female patients in both periods while for bevacizumab, 42% of claims were for female patients before the policy change and 43% afterward. There were also more trastuzumab claims for treating breast cancer (96%) than gastric cancer (4%). Bevacizumab was used at the treatment for 86% to 87% of the claims for colorectal cancer and 13% to 14% of the claims for lung cancer in both observed periods.

The time series analysis demonstrated a significant preintervention monthly increase in biosimilar use of 0.65% (95% CI, 0.48%-0.83%). The postintervention slope change of 0.33% (95% CI, 0.07%-0.58%) and the overall postintervention slope of 0.98% per month (95% CI, 0.8%-1.16%) also were significant, showing a continued increase in biosimilar uptake.

Bevacizumab had a significant increase in biosimilar usage before the policy intervention, with a slope of 1.56% per month (95% CI, 1.44%-1.69%). The level change postintervention was 0.16% (95% CI, –1.52% to 1.83%). The slope change postintervention was –0.18% (95% CI, –0.41% to 0.06%), which was not significant. The postintervention slope remained positive and significant at 1.38% per month (95% CI, 1.17%-1.60%).

The prices for the originator and biosimilar versions of trastuzumab, as of April 2022, were $231 (¥34,670) and $127 (¥19,118) for 150 mg, respectively. Bevacizumab’s originator and biosimilar were priced at $811 (¥121,608) and $363 (¥54,403) for 400 mg, respectively.

The results may not be fully representative of the overall Japanese population, and the medications may not have been analyzed long enough to capture the effects of the policy over the long term. Also, the outcomes are tied to specific characteristics of Japanese health care and reimbursement systems that might not be directly applicable to the differing health care infrastructures, regulatory environments, and approaches to biosimilar promotion of other countries. The study also is limited by the external validity of our conclusions, especially since each country has a unique policy landscape that could influence the effectiveness of similar interventions.

“It is crucial for policy makers to design reimbursement strategies that are specifically tailored to the characteristics of each biosimilar to optimize their effectiveness,” study authors concluded.

1. Mamiya H, Fukasawa T, Kawakami K. Effects of reimbursement add-on policies on trastuzumab and bevacizumab biosimilar adoption in Japanese oncology setting. 

2025;46:101090. doi:10.1016/j.vhri.2025.101090

2. Yusuke Kajimoto, Honda K, Nozawa K, Mukai M, Teng L, Igarashi A. Use of anticancer therapies and economic burden near the end of life in Japan: results from claims database. 

. 2022;8:e2200227. doi:10.1200/go.22.00227

Articles

Trastuzumab biosimilars saw significant market uptake in Japan after reimbursement incentives were implemented, but bevacizumab biosimilars did not experience a similar response.

Trastuzumab Biosimilar Adoption Increased in Japan Due to Reimbursement

Elena Wolff-Holz, MD

Elena Wolff-Holz, MD, global head of clinical development at Biocon Biologics, discussed the recent approval of 

 as a biosimilar to reference ustekinumab (Stelara) to treat psoriasis.


Wolff-Holz emphasized the comparable efficacy and safety results observed, including pre- and postswitch data, while acknowledging challenges in patient recruitment and navigating diverse global regulatory requirements.

This transcript was lightly edited for clarity; captions were auto-generated.

What specific clinical end points or patient-reported outcomes did you find most compelling in support of the study comparing BMAb-1200 with reference ustekinumab?

Well, maybe just a few introductory statements, so BMAb-1200 is now an approved drug. It just got recently approved and is called Yesintek [ustekinumab-kfce] here in the United States and will also be launched in Europe and Japan in the next few weeks.


The clinical basis, the clinical study, the phase 3 trial that was conducted in support of the marketing authorization application, was a clinical trial that lasted 52 weeks. It was a double-blind randomized trial in 384 patients, and they were rerandomized; those patients that received the originator drug Stelara were rerandomized at week 16 to either continue on the Stelara or get the BMAb-1200, and then all patients were followed in a blind fashion until week 52.


In terms of end points, the primary end point, and I think that was the most compelling, was at week 12. That's important because it's sort of in the steep part of the dose-response curve, and you can really, if there was a difference, you would detect it at that time point. Actually there was, in terms of change of the PASI [Psoriasis Area and Severity Index] score from baseline, there was absolutely no difference.


The FDA and also EMA, they have certain requirements on how they define confidence intervals. The 2 drugs must be within this confidence interval, and [for] FDA plus/minus 10% is allowed. We had a difference of 0.68%, so that's very compelling primary end point results. Above and beyond, we've also looked at week 4, 8, 16, and 20-week data, and that was also highly similar. We looked at preswitch and postswitch data, and again, the switching would not have any impact with regard to the PASI score or safety or immunogenicity.


These are all very important findings, and I would think, in summary, those are the most important ones, but there's also the PsA [psoriatic arthritis], actually, and they were also comparable. All of this gives a very comprehensive story.

What were the most significant challenges encountered during the study, and how were they addressed? What lessons were learned that could benefit future biosimilar development?

This was a global study at 41 centers, 5 countries, and 384 patients, so recruiting these patients on time. We had a global development that would satisfy all the legislations, including PMDA [Pharmaceuticals and Medical Devices Agency], that is Japan's regulatory body. At that time, we were asked to have at least 15% Japanese patients, and that was a challenge to include. Luckily, the Japanese regulators now have changed this demand. It's no longer required. It also introduced heterogeneity. That's something we would change, and we would be allowed to change.

Otherwise, I think anything that enhances inspection readiness would be of advantage. I think we've implemented checkpoints already in the trial, but this is something also in terms of monitoring continuity from the CRO [contract research organization] site to the sites. I think that's something I would take more care even to have this continuity so one particular CRA [clinical research associate] or CRM [clinical research management] [is] really being available for the entire study and beyond to carry through, also the inspections.

Elena Wolff-Holz, MD, global head of clinical development at Biocon Biologics, discussed the approval of BMAb-1200, a biosimilar to reference ustekinumab for psoriasis, highlighting comparable efficacy and safety data while noting challenges in global patient recruitment and regulatory navigation.

The Global Biosimilar Development and Approval of Yesintek With Elena Wolff-Holz, MD

Here are the top 5 biosimilar articles for the week of April 7, 2025.

 Mvasi and Zirabev provided cost savings for metastatic colorectal cancer (mCRC) treatment without compromising effectiveness.

: High adherence rates, comparable clinical effectiveness, and cost savings have marked the early adoption of adalimumab biosimilars in the US, particularly in formulary-driven transitions, as shown in 2 retrospective studies presented at the 

Academy of Managed Care Pharmacy annual meeting (AMCP 2025)

, the market continues to evolve with expanded treatment options, cost savings, and a flurry of new competitors—yet regulatory challenges, market dynamics, and patient accessibility remain key hurdles to unlocking its full potential.

 Ongavia exhibited significantly less improvement in visual acuity and retinal thickness compared with aflibercept (Eylea) in treating neovascular age-related macular degeneration (nAMD), highlighting a potential trade-off between economic savings and clinical efficacy.

—fueled by its biosimilar portfolio and global expansion—highlights the booming profitability of biosimilars despite financial hurdles.

The Top 5 Biosimilar Articles for the Week of April 7

Here are the top 5 biosimilar articles for the week of March 31, 2025.

 demonstrated comparable efficacy, safety, and immunogenicity to reference drug Tysabri in patients with relapsing-remitting multiple sclerosis (RRMS), supporting its potential as a cost-effective treatment option.

 products does not affect drug effectiveness or treatment duration in patients who have psoriasis, according to a Danish study.

 lead biosimilar approvals because of their large market size, well-defined regulatory pathways, and technological feasibility, whereas other biologics encounter development challenges but may see increased adoption as regulatory frameworks advance.

denosumab biosimilars, Conexxence/Bomyntra

 (denosumab-bnht), expanding treatment options for osteoporosis, bone metastases, and other bone-related conditions, amidst a flurry of similar approvals and legal settlements.

The Top 5 Biosimilar Articles for the Week of March 31

The ranibizumab biosimilar Ongavia exhibited significantly less improvement in visual acuity and retinal thickness compared with aflibercept (Eylea) in treating neovascular age-related macular degeneration (nAMD), highlighting a potential trade-off between economic savings and clinical efficacy. | Image Credit: Witoon - stock.adobe.com

Ranibizumab biosimilar (Ongavia) offers a lower cost alternative for neovascular age-related macular degeneration (nAMD) treatment, resulting in significantly less visual improvement and reduced retinal thickness reduction compared with aflibercept (Eylea), especially when strict monthly injection schedules were not maintained, according to a study published in 

Individuals aged 50 years and older have an increased risk of developing age-related macular degeneration (AMD) since it is the leading cause of severe visual impairment and blindness, accounting for over 8.7% of global blindness. In nAMD, the abnormal blood vessels grow under the retinal pigment epithelium and into the macula, causing fluid leakage, hemorrhage, and fibrosis, which leads to central vision impairment.

Vascular endothelial growth factor (VEGF) plays a vital role in the pathogenesis of nAMD, and anti-VEGF therapies are a common treatment for nAMD to prevent angiogenesis and fluid leakage to preserve macular function and vision. The FDA approved the anti-VEGF agents ranibizumab (Lucentis) and aflibercept in 2006 and 2011, respectively.

The patent for ranibizumab, a humanized monoclonal antibody fragment targeting VEGF growth factor A, expired in June 2020, allowing the development of biosimilars. Ongavia is a ranibizumab biosimilar that was developed by Teva Pharmaceuticals for the treatment of several ophthalmic conditions by the UK Medicines & Healthcare Regulatory Agency in May 2022.

 Ongavia costs a lot less than the originator, offering an economically attractive option for health care systems under financial strain.

“We aim to provide insights into the comparative performance of these anti-VEGF agents under real-world conditions, addressing both clinical efficacy and resource implications,” study authors stated.

Researchers conducted a single-center retrospective audit at a tertiary hospital ophthalmology medical retina unit and evaluated 2 types of intravitreal anti-VEGF injections initiated for new presentations of nAMD to the medical retina department. The study included 12 months of post-initial intravitreal injection outcome data from August 2022 to August 2024.

There was a total of 62 eyes that met the inclusion criteria, with 34 women and 28 men. Patients receiving Eylea (n = 36) had a significantly greater improvement in best-corrected visual acuity Early Treatment Diabetic Retinopathy Study (ETDRS) letters of 7.08 (4.12) compared with Ongavia (n = 26) with –1.9 (3.31; 

 = .018). The mean initial and end point BCVA for Eylea was 50.7 and 57.8 ETDRS letters, respectively. The mean initial and end point BCVA for Ongavia was 53.7 and 51.8 ETDRS letters, respectively.

Eylea demonstrated a greater reduction in central retinal thickness (CRT), decreasing it by 116.21 μm (35.61 μm), compared with Ongavia, which reduced CRT by 51.41 μm (22.21 μm; 

 = .002). The mean initial and end point CRT for Eylea was 330.8 μm and 214.6 μm, respectively. The mean initial and end point CRT for Ongavia was 318.8 μm and 267.7 μm, respectively.

On average, patients received injection intervals of 9.49 weeks for Eylea compared with 8.17 weeks for Ongavia. Researchers prescribed 164 out of 171 (96%) Ongavia injections at 4-week intervals, compared with 110 out of 207 (53%) Eylea injections. They prebooked the first 3 intravitreal injections for 4-week intervals but administered the second injection at an average of 5.3 weeks for Ongavia and 5 weeks for Eylea. They administered the third injection at an average of 6.4 weeks for Ongavia and 6.6 weeks for Eylea.


Regarding costs, biosimilar launches have resulted in both a 53% market share in biosimilar markets and a 53% reduction in average drug costs after 5 years of biosimilar competition, based on Samsung Bioepis’ First Quarter 2025 Biosimilar Market Report.

 However, data indicate that immunology and ophthalmology biosimilars yielded smaller discounts than oncology biosimilars.


The study may be limited by potential selection bias that could affect the visual gains data along with logistical challenges.

“Future studies should perform a thorough cost analysis to investigate the long-term cost implications and clinical efficacy of biosimilars under various administrative constraints to help guide their implementation,” study authors concluded.

1. Bilal A, Bilal M, Usman D, Elahi A, Al-Bermani A. A tertiary centre's experience with using ranibizumab biosimilar compared to aflibercept for neovascular age-related macular degeneration: a retrospective study. 

. 2024;16(12):e75586. Published 2024 Dec 12. doi:10.7759/cureus.75586

2. Jeremias S. Teva’s Lucentis biosimilar gains UK approval. The Center for Biosimilars

. May 17, 2022. Accessed March 31, 2025. 

https://www.centerforbiosimilars.com/view/teva-s-lucentis-biosimilar-gains-uk-approval

3. Jeremias S. Biosimilars drive cost savings and achieve 53% market share across treatment areas. The Center for Biosimilars. January 16, 2025. Accessed March 31, 2025. 

https://www.centerforbiosimilars.com/view/biosimilars-drive-cost-savings-and-achieve-53-market-share-across-treatment-areas

The ranibizumab biosimilar Ongavia exhibited significantly less improvement in visual acuity and retinal thickness compared with aflibercept (Eylea) in treating neovascular age-related macular degeneration (nAMD), highlighting a potential trade-off between economic savings and clinical efficacy.

Ranibizumab Biosimilar Shows Reduced Efficacy vs Aflibercept in nAMD

PBM Evolution Towards Value-Based Care Shifts to Transparent Pharmacy Pricing

Josh Canavan, PharmD, head of pharmacy at RazorMetrics, and Chris O'Dell, senior vice president of market solutions at Turquoise Health, foresee pharmacy benefit managers (PBMs) transitioning to value-based care, prioritizing patient outcomes and transparency.


Canavan highlights a shift from cost-centric models to those emphasizing patient health, while O'Dell predicts PBMs will eventually disclose contract rates, similar to health care price transparency, fostering informed discussions and potentially optimizing biosimilar adoption based on cost-effectiveness.

How do you anticipate the role of PBMs will evolve, and do you foresee a significant shift towards more transparent and value-based contracting models?

I think PBMs are going to start to really look at long-term patient outcomes. Previously, PBMs have looked at the bottom line, the lowest cost medication, the lowest net cost that they can get. With the evolving landscape, we'll start to see more patient-centric medicine, and it focuses more on what the provider looks at.


Quality measures are becoming more important to PBMs. For example, with diabetic patients, the PBM may look at the patient on metformin; they're getting prescribed a medication that covers their disease, but with the focus on patient outcomes, now the PBM can start to look at if their A1C is under control. Has the patient received an eye exam? Is their blood pressure controlled?


There are more outcomes that they can look at that are focused on the patient and focused on how the provider can help the patient than simply, "Is the patient on a low-cost medication?"

The third one is PBM strategies aligning better with health professionals' goals. The way that the provider works is better aligned with how the PBM will measure this. The provider looks at the A1C, the provider wants the patient to have an eye exam, the provider wants the patient's blood pressure under control. If the PBM is aligned with what the provider wants, we're all on the same page here.

One of the things that might impact this at first is it's harder to measure these. At first, you may not be able to see the benefit of some of these longer-term goals, and so that might change the key performance metrics for some of these. But eventually, over time, we'll see major improvements in patient outcomes, which saves everybody money.


 I see PBMs having a lot of the same reactions that hospitals and payers did when the first price transparency data came out back in 2021. The first reaction that they had was, "I'm going to drag my feet; I'm not going to publish this data; I'm going to hide it. This is my secret sauce; these contracts are my secret sauce, and I'm not going to put them out there." Slowly, everyone started publishing their contracts, and now it's all visible.

I think that this idea that someone would be caught getting paid too much really didn't turn out to be true. It just is that now we have a really good understanding of who's making what along the way.

The first thing is, I think you're going to see a slow move toward it where there will be a lot of feet dragging, but at some point, you're going to see all of the PBMs begin to publish their contract rates with the pharmacies and with the payers. Things like spread pricing or rebates, which used to be fought over but probably fought over anecdotally, are now going to be highly transparent so that we can have a really good discussion about it.

There won't just be this mentality of "PBM bad"; it'll be like, "Well, it's complex; let's see what they're making." It'll be different by product, and it'll be different by marketing, and it'll be different by PBM, but we'll get to see all of that.

Around whether and how that will impact biosimilar adoption, I think that transparency will dictate where on the formulary you're seeing these biosimilars show up. There's a little bit of this model of "provide a big rebate and try to get the best position with the payer so that you're favorable on the formulary." I think that will probably be the model that gets most questioned. 

At the end of the day, if these are all clinically efficacious and you can see exactly what the rebate and discount model is along the way, now you don't have these weird back door arbitrage where it's the biggest kickback that means that the product is getting the best utilization. You can just get the lowest manufacturing cost equals the highest adoption. Hopefully, this is what we're all shooting for because it results in less out-of-pocket [costs] for the patient, or at least more transparency into what you'll pay before you get the [drug].

Josh Canavan, PharmD, RazorMetrics, and Chris O'Dell, Turquoise Health, predict pharmacy benefit managers (PBMs) will evolve toward value-based care, mirroring the broader shift toward open-cost structures.

PBM Evolution Toward Value-Based Care Shifts to Transparent Pharmacy Pricing

The Top 5 Biosimilar Articles for the Week of March 24

: Patients with moderate to severe plaque psoriasis who switched between the 

 and reference adalimumab did not impact immunogenicity, safety, or efficacy following up to 4 switches between both drugs.

 as the most effective strategy for reducing costs and increasing biosimilar uptake in the retail setting, while price-linked discounts and prescribing quotas have shown mixed or uncertain results.

: Patients with diabetic macular edema previously treated with a 

 in India experience comparable safety and efficacy after being switched to another ranibizumab biosimilar, demonstrating real-world safety of biosimilar-to-biosimilar switching.

Global biosimilar regulatory harmonization

 will be needed to reduce development costs and improve patient access, despite challenges posed by differing national requirements and regulatory frameworks, according to review authors.

 matched reference ustekinumab in efficacy and safety, while an adalimumab biosimilar proved interchangeable with reference adalimumab, according to posters at the American Academy of Dermatology (AAD) annual meeting.

Here are the top 5 biosimilar articles for the week of March 24, 2025. 

The FDA approved another set of denosumab biosimilars, Conexxence/Bomyntra (denosumab-bnht) expanding treatment options for osteoporosis, bone metastases, and other bone-related conditions, amidst a flurry of similar approvals and legal settlements. | Image Credit: gguy - stock.adobe.com

The FDA has approved Fresenius Kabi Biopharma's denosumab biosimilars, Conexxence and Bomyntra (denosumab-bnht), for all indications of the reference products Prolia and Xgeva, respectively, further expanding access to more affordable treatment options for patients with osteoporosis, bone metastases, and other bone-related conditions.

Fresenius Kabi Biopharma announced the approval of its Biologics License Application for both denosumab biosimilars and a global settlement with Amgen.


“This marks our sixth FDA biosimilar approval, expanding our portfolio to provide more affordable therapies to patients in the US,” Sang-Jin Pak, MD, president of Fresenius Kabi Biopharma, said.

In March 2024, the FDA granted approval to Wyost/Jubbonti (denosumab-bddz; GP2411), marking it as the first biosimilar to reference Xgeva/Prolia (denosumab) in the US.

 A month ago, the FDA and the European Medicines Agency also approved another pair of biosimilars, Ospomyv/Xbryk (denosumab-dssb; SB16), referencing Prolia/Xgeva (denosumab).

 The FDA also approved Celltrion's denosumab biosimilars, Stoboclo and Osenvelt (denosumab-bmwo), earlier this month, again referencing Prolia and Xgeva, respectively.

Two comparative clinical studies supported the newest approval, which was based on comprehensive analytical development and similarity assessment.

 One study measured pharmacokinetic, pharmacodynamic (PD), and immunogenicity among healthy volunteers, and the second study measured efficacy, PD, safety, and immunogenicity in women with postmenopausal osteoporosis.

The FDA approved Conexxence (denosumab-bnht) for use in various adult patient populations at high risk for fractures, including osteoporosis, individuals undergoing certain cancer treatments that affect bone density, and patients receiving long-term glucocorticoid therapy. For dosage, clinicians administer a 60 mg/mL solution via a single-dose prefilled syringe.


Patients with postmenopausal osteoporosis experienced adverse events (AEs) including back pain, hypercholesterolemia, musculoskeletal pain, and cystitis. Men with osteoporosis experienced AEs such as back pain, arthralgia, and nasopharyngitis. Patients with glucocorticoid-induced osteoporosis commonly experienced AEs such as back pain, hypertension, bronchitis, and headache. Those with hormone ablation for cancer most commonly experienced AEs of arthralgia and back pain in patients with bone loss.

The FDA approved Bomyntra (denosumab-bnht) to prevent skeletal-related events in adult patients with multiple myeloma and bone metastases from solid tumors. The FDA also approved it to treat hypercalcemia of malignancy refractory to bisphosphonate therapy and giant cell tumor of bone in adults and skeletally mature adolescents.


Patients receive the approved dosage as a 120 mg/1.7 mL solution via single-dose vial or prefilled syringe. Those with bone metastasis from solid tumors commonly experienced fatigue/asthenia, hypophosphatemia, and nausea. Patients with multiple myeloma reported diarrhea, nausea, anemia, back pain, thrombocytopenia, peripheral edema, hypocalcemia, upper respiratory tract infection, rash, and headache.


Patients with giant cell tumor of bone experienced arthralgia, headache, nausea, back pain, fatigue, and pain in extremity. Finally, patients with hypercalcemia of malignancy experienced nausea, dyspnea, decreased appetite, headache, peripheral edema, vomiting, anemia, constipation, and diarrhea.


Fresenius Kabi Biopharma plans to launch the denosumab biosimilars in the US market mid-2025 and in Europe in the second half of 2025, pending regulatory approvals.

1. Fresenius receives FDA approval for their denosumab biosimilars and secures global settlement agreement. News release. Business Wire; March 27, 2025. Accessed March 27, 2025. 

https://www.businesswire.com/news/home/20250327908783/en/Fresenius-Receives-FDA-Approval-for-their-Denosumab-Biosimilars-and-Secures-Global-Settlement-Agreement

2. Jeremias S. FDA approves first denosumab biosimilars. The Center for Biosimilars

. March 5, 2024. Accessed March 27, 2025. 

https://www.centerforbiosimilars.com/view/fda-approves-first-denosumab-biosimilar

3. Jeremias S. FDA, EMA approve second pair of denosumab biosimilars. The Center for Biosimilars. February 17, 2025. Accessed March 27, 2025. 

https://www.centerforbiosimilars.com/view/fda-ema-approve-second-pair-of-denosumab-biosimilars

4. Santoro C. FDA approves denosumab biosimilars Stoboclo and Osenvelt. 

. March 4, 2025. Accessed March 27, 2025. 

https://www.ajmc.com/view/fda-approves-denosumab-biosimilars-stoboclo-and-osenvelt

The FDA approved another set of denosumab biosimilars, Conexxence/Bomyntra (denosumab-bnht), expanding treatment options for osteoporosis, bone metastases, and other bone-related conditions, amidst a flurry of similar approvals and legal settlements.

FDA Approves Another Pair of Denosumab Biosimilars, Conexxence and Bomyntra 

Biosimilar natalizumab demonstrates comparable efficacy, safety, and immunogenicity to reference drug, Tysabri, in patients with relapsing-remitting multiple sclerosis (RRMS), supporting its potential as a cost-effective treatment option. | Image Credit: Vitalii Vodolazskyi - stock.adobe.com

Natalizumab-sztn (Tyruko; Sandoz) expressed efficacy and safety in patients with relapsing-remitting multiple sclerosis (RRMS) to confirm matching immunogenicity profiles between the biosimilar and reference natalizumab (Tysabri; Biogen), according to a study published in 

Multiple sclerosis (MS), a chronic inflammatory disease, is characterized by central nervous system lesions that can cause severe physical, cognitive, and other neurological defects.

 The approval of a biologic medicine in the 1990s changed MS treatment with disease-modifying therapies (DMTs). As reference biologic medications lost market exclusivity, biosimilars to branded reference biologics entered the market, potentially offering more cost-effective treatment options and expanding access to high-efficacy DMTs in MS.

Two randomized, comparative clinical trials compared natalizumab-sztn and reference natalizumab within the clinical development program of biosimilar natalizumab. The Antelope study (NCT04115488) enrolled patients with RRMS, and the second study measured pharmacokinetics (PK) and pharmacodynamics (PD) in healthy patients (EudraCT: 2019-003874-15).

Researchers conducted the Antelope study, a multicenter, double-blind, active-controlled, randomized, parallel-group trial, to assess the similarity in efficacy, safety, and immunogenicity of prolonged treatment with biosimilar natalizumab and the European (EU) approved reference natalizumab. Patients with RRMS were randomized to receive intravenous infusions of either 300 mg biosimilar or 300 mg of reference natalizumab every 4 weeks for 12 visits, totaling 12 infusions. Researchers rerandomized reference natalizumab at week 24 and switched 30 patients to continue treatment with the biosimilar for 24 weeks.

Researchers conducted a single-dose, randomized, double-blind, parallel-group PK/PD study in healthy patients (n = 453) to demonstrate similarity between natalizumab-sztn and US-licensed or EU-approved reference natalizumab. Patients were randomized based on their body weight to receive a 1 hour, 3 mg/kg infusion of biosimilar natalizumab, US reference product, or EU reference product.

The Antelope study enrolled 264 patients with RRMS, with 131 patients receiving biosimilar natalizumab and 133 patients receiving the EU reference product for over 48 weeks. The PK/PD comparative study enrolled 450 healthy participants—149 participants received biosimilar natalizumab, 150 received the US reference product, and 151 received the EU reference product.

Natalizumab-stzn and the EU reference product showed similar incidences of overall anti-drug antibody (ADA) (79.4% vs 73.7%, respectively) and neutralizing antibodies (NAb) (68.7% vs 66.2%, respectively) at week 24. The PK/PD comparative study found no detectable differences in ADA or NAb response dynamics between the biosimilar group and the US or EU reference natalizumab, supporting these findings. Natalizumab-sztn, US natalizumab, and EU natalizumab yielded similar overall incidences of treatment-emergent ADA (87.2%, 92%, and 86.8%, respectively).

Antelope showed that switching patients with RRMS from EU natalizumab to the biosimilar did not impact their treatment-related ADA/NAb immune or clinical responses. Before switching, 43.4% of patients in the switch arm (n = 30) tested ADA-positive, and 30% tested NAb-positive at week 24. Additionally, the PK/PD study demonstrated a matching overall incidence of ADA between treatment groups and matching ADA titer profiles over time.

The Antelope study reported few infusion-related reactions, with 10 occurring in the biosimilar group and 5 in the EU reference group. Patients switching from EU natalizumab to biosimilar natalizumab at week 24 experienced erythema and hypersensitivity reactions. The PK/PD study reported no hypersensitivity reactions.

The study highlights the absence of standardized methodology and reference materials for ADA testing, and the researchers cautioned to approach comparison of different assay outputs with caution. Post-authorization pharmacovigilance should monitor the ongoing evaluation of the incidence of progressive multifocal leukoencephalopathy (PML) for natalizumab-sztn so that the prescribing information for all natalizumab products advises close monitoring for symptoms of PML.

“We have demonstrated that the immunogenicity profiles of biosim-NTZ and ref-NTZ are indistinguishable in healthy subjects and patients with RRMS in the tested setting. These findings confirm the biosimilarity of biosim-NTZ and ref-NTZ with no safety or efficacy concerns identified to be associated with immunogenicity,” the study authors concluded.

1. Chamberlain P, Hemmer B, Höfler J, et al. Comparative immunogenicity assessment of biosimilar natalizumab to its reference medicine: a matching immunogenicity profile. 

. 2024;15:1414304. Published 2024 Dec 19. doi:10.3389/fimmu.2024.1414304

2. Biosimilar approvals. The Center for Biosimilars

. January 7, 2025. Accessed March 24, 2025. 

https://www.centerforbiosimilars.com/biosimilar-approvals

3. Greenberg B, Giovannoni G. A place for biosimilars in the changing multiple sclerosis treatment landscape. 

. 2023;77:104841. doi:10.1016/j.msard.2023.104841

Biosimilar natalizumab demonstrated comparable efficacy, safety, and immunogenicity to reference drug Tysabri in patients with relapsing-remitting multiple sclerosis (RRMS), supporting its potential as a cost-effective treatment option.