Cameron Santoro is an associate editor for The Center for Biosimilars

Cameron Santoro

The Top 5 Biosimilar Articles for the Week of August 5

 a lot of discussion regarding biosimilar policies, in both the US and abroad, as well as 3 highly anticipated FDA approvals.

 predicted in 2025, several originator biologics set to face biosimilar competition in the next few years are projected to increase their list prices, according to 

Vizient’s Pharmacy Market Outlook Report for Summer 2024

 Value-driven health care strategies in Singapore’s public institutions have significantly increased biosimilar adoption, leading to reduced treatment costs and substantial savings for the health care system, 

 now available has helped countless patients deal with diseases for which traditional treatments were unsatisfactory. Individuals who have autoimmune diseases, cancer, and diabetes have benefited, as have those with previously untreatable genetic diseases. The most complex biologics first entered the market in the 1980s and 1990s, and for this reason, many of their patents are expiring. The concept of biosimilars was a rational idea that loosely mimicked the idea of generic drugs. However, because biologics are large, 3-dimensional, complex molecules, it took some time for regulatory agencies around the world to develop appropriate regulations.

 on glycan profiling of monoclonal antibodies (Mabs) receives praise and recommendations from Sarfaraz K. Niazi, PhD.

To read all of these articles and more, visit 

Videos

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

In a comprehensive analysis,the biosimilar SB15 exhibited high similarity to reference aflibercept in terms of physicochemical and biological properties. | Image Credit: 

The physicochemical and biological properties of SB15, a biosimilar product referencing aflibercept (Eylea), was highly similar to aflibercept reference products in the US and European Union (EU) in a study from

The findings support safe and effective use of SB15, according to the authors. 

Both the FDA and European Medicines Agency (EMA) approved aflibercept, aVEGF inhibitor, for a a range of ocular diseases such as neovascular age-related macular degeneration (nAMD), macular edema following retinal vein occlusion, diabetic macular edema, and diabetic retinopathy.

The FDA approved aflibercept in November 2011, along with Japan, Australia, Switzerland, and other countries.

 However, the EMA did not approve aflibercept until the following year, in November 2012.

More recently, Samsung Bioepis developed SB15, a biosimilar to reference aflibercept.

Earlier this year, a multi-region study proved comparable safety, efficacy, immunogenicity, and pharmacokinetics in SB15 vs reference aflibercept for first-line treatment after patients switched from aflibercept to SB15 in nAMD.

Aflibercept is an anti-VEGF agent that harbors the binding domains of vascular endothelial growth factor (VEGF) receptors 1 and 2 while blocking all VEGF-A isoforms, VEGF-B, and placental growth factor.

 The biosimilar, SB15, is produced by a recombinant DNA technology and was developed to reference aflibercept.

An analytical panel was used to comprehensively characterize SB15 compared with the US/EU-sourced aflibercept.

 Every sample included in the study was handled in a sterile manner in a biological safety cabinet. 

The analysis examined primary structure, higher-order structure, physicochemical properties, and functional activities. The molecular weights of SB15 and US/EU aflibercept were comparable for the deglycosylated and reduced samples.

The intact molecular weights of SB15 and US/EU aflibercept were also comparable based on single-chain molecular weight, disulfide linkage, and site-specific N-glycosylation analysis. The primary structure did not have any meaningful differences observed in biological activities.

Higher-order structural comparisons using circular dichroism and differential scanning calorimetry revealed high similarity between SB15 and the reference aflibercept products. Circular dichroism analyzes protein structure through polarized light,

while differential scanning calorimetry assesses protein stability by measuring changes in heat flow.

In terms of size and charge heterogeneity, there were no meaningful differences in the physicochemical properties between SB15 and its reference product.

 The relative quantity of high molecular weight of SB15 (0.9%) were lower than US/EU aflibercept (2.4 and 2.5%, respectively). While there was a difference in charge heterogeneity, it was not associated with any changes in biological activities.

Biological activities such as mechanism of action–related binding activities, potencies, and fragment crystallizable–related biological functions were similar between SB15 and the reference product.

There were no significant differences between SB15, US aflibercept, and EU aflibercept in terms of VEGF-A 165 neutralization potencies, and all SB15 samples were within the US/EU similarity range. There were relative FcRn binding affinities for all SB15 tested samples, which were within the US/EU similarity range.

There were also no significant differences in VEGF family ligands binding activities between SB15 and US/EU aflibercept.

The authors concluded that their state-of-the-art analysis demonstrated highly similar results between SB15 and US/EU aflibercept. These results support the biosimilarity of SB15 with respect to US/EU aflibercept.

“The structural, physicochemical, and biological similarity between SB15 and US/EU aflibercept were evaluated,” the authors wrote. “Comprehensive analytical characterization of SB15 and US/EU aflibercept were implemented and the results demonstrated that SB15 and US/EU aflibercept were highly similar. The results of the analytical characterization provide the foundation for the totality of evidence to support the biosimilarity of SB15 with respect to US/EU aflibercept.”

1. Lee H, Huh J, Kim D, et al. Analytical characterization for similarity assessment between an aflibercept biosimilar SB15 and reference product (Eylea).

. 2024;13(8):2209-2225. doi:10.1007/s40123-024-00977-0

2. Eylea (aflibercept) injection approved for the treatment of wet age-related macular degeneration in Europe. News release. Regeneron. November 27, 2021. Accessed August 5, 2024. 

https://investor.regeneron.com/news-releases/news-release-details/eylear-aflibercept-injection-approved-treatment-wet-age-0

3. Sadda SR, Bradvica M, Vajas A, et al. Biosimilar SB15 versus reference aflibercept in neovascular age-related macular degeneration: 1-year and switching results of a phase 3 clinical trial. 

. 2023;8(1):e001561. doi:10.1136/bmjophth-2023-001561

4. Santoro C. SB15 effective, safe in treating nAMD, before, after switching. The Center for Biosimilars

. February 1, 2024. Accessed August 5, 2024. 

https://www.centerforbiosimilars.com/view/sb15-effective-safe-in-treating-namd-before-after-switching

5. Woo SJ, Bradvica M, Vajas A, et al. Efficacy and safety of the aflibercept biosimilar SB15 in neovascular age-related macular degeneration: aphase 3 randomized clinical trial. 

. 2023;141(7):668–676. doi:10.1001/jamaophthalmol.2023.2260

6. Hurlburt N. Circular dichroism. Chemistry LibreTexts. October 2, 2013. Accessed August 7, 2024. 

https://chem.libretexts.org/Bookshelves/Physical_and_Theoretical_Chemistry_Textbook_Maps/Supplemental_Modules_(Physical_and_Theoretical_Chemistry)/Spectroscopy/Electronic_Spectroscopy/Circular_Dichroism

7. Differential scanning calorimeters. TA Instruments. Accessed August 7, 2024. 

https://www.tainstruments.com/products/thermal-analysis/differential-scanning-calorimeters/

Articles

In a comprehensive analysis, the biosimilar SB15 exhibited high similarity to reference aflibercept in terms of physicochemical and biological properties.

SB15 Biosimilar Demonstrates High Similarity to Reference Product Aflibercept

The Top 5 Biosimilar Articles for the Week of July 29

 with GoodRx to offer its unbranded adalimumab biosimilar to patients at an exclusive low price; a new ustekinumab biosimilar launches in Europe; and Mexican officials approve a bevacizumab biosimilar.

 showed similar pharmacokinetic and safety profiles compared with the reference product Trulicity in healthy Chinese participants, according to a phase 1 analysis.

 that references Soliris (eculizumab), for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS).1

 were $452,611 over 3 years, driven by decreased drug acquisition costs and a utilization shift from reference to biosimilar natalizumab.

Here are the top 5 biosimilar articles for the week of July 29, 2024.

Ivo Abraham, PhD, RN. 

Ivo Abraham, PhD, RN, director of the Center for Health Outcomes and PharmacoEconomic Research at the University of Arizona Cancer Center acknowledged the responsibility of the FDA regarding safety and efficacy in drug approvals in an interview with The Center for Biosimilars

Abraham does not advocate for adopting the World Health Organization (WHO) guidelines entirely but sees promise in recent FDA movements on interchangeability since they propose the use of statistical modeling and shifting the clinical evidence burden to post-approval safety monitoring to expedite approval.

This transcript has been lightly edited for clarity. 

What specific regulatory roadblocks are hindering the rapid approval of biosimilars, and how can we collaborate with regulatory bodies to streamline the process? 

What we need to remember is that the FDA is the watchdog for everything that is related to drugs. It has an enormous responsibility and accountability, also to Congress, in terms of providing safe—in first instance—and then also effective drugs and that applies to biosimilars as well.

In a certain way, I expect the changes in terms of approval processes, and market entry, and post-approval monitoring will gradually, in an incremental way, stepwise, loosen up, for lack of a better word. So, biosimilar approval 2.0 will emerge at some point in time.

I'm not ready to be quoted saying that the FDA should adopt the WHO guidelines because the influence of the FDA and the European Medicines Agency (EMA) is global. Yes, we need to provide access to biosimilars in the rest of the world as well, but it needs to come from a very high level of standards related to quality and equivalence.

If you look, for instance, at issues—and that's an area where we see some movements within the FDA, and that has to do with interchangeability—there's a recent document that came out, and getting the interchangeability may, at some point in time, become a lot easier.

It can actually be done much easier because interchangeability can be modeled statistically. We have developed—while it's still in the prototype phase—a model that you could statistically create scenarios of interchangeability, take the data that are available, whether they're just pre-approval data, whether they're real-world clinical data, safety and effectiveness data, and model whether there is a risk and what that risk is of an adverse outcome related to interchangeable use of biosimilars.

It's also important then to shift the clinical evidence burden to safety post-approval. We can accelerate the process, for instance, as we do for some other drugs, and say, "Okay, we'll approve your biosimilar, but you are going to be watching yourself and reporting data to us based upon your biosimilars." In that process to develop—and I think that it is critical to develop channels for post-approval monitoring that go beyond voluntary reporting—make it required for the first 2 years on the market.

It doesn't mean that biosimilar companies would need to start sponsoring post-approval prospective studies or whatever because those are expensive. But you can do that to some extent with claims databases, electronic health records, to see what pops up in terms of safety signals as we use biosimilars.

Ivo Abraham, PhD, RN, University of Arizona Cancer Center, recognizes the importance of stringent safety measures for biosimilar approvals. However, he advocates for utilizing statistical models and placing emphasis on postmarket safety data collection.

Streamlining Biosimilar Approvals by Balancing Safety, Speed

The Top 5 Biosimilar Articles for the Week of July 22

 Samsung Bioepis’ Epysqli (eculizumab-aagh), marking the second US approval for a biosimilar referencing Soliris (eculizumab).

 or chronic inflammatory rheumatic disease treated with reference adalimumab who were switched to the 

 CT-P17 generally believed the switch was a treatment necessity. Higher satisfaction rates were observed among those who were convinced of the necessity compared with those with greater concerns about treatment.

 aim to save time and money for manufacturers in the Middle East and North Africa (MENA), but hesitancy among nations to adopt the guidelines is stifling market development of biosimilars.

challenges with pharmacy benefit managers

 (PBMs) that plague the biosimilar industry and new legislation that attempts to reform their practices and encourage biosimilar adoption.

Economic evaluations of biosimilar disease-modifying antirheumatic drugs (DMARDs) suggest cost-effectiveness for patients with rheumatoid arthritis (RA) who did not respond well to methotrexate, potentially 

improving patient outcomes and health care affordability.

Here are the top 5 biosimilar articles for the week of July 22, 2024. 

The Top 5 Biosimilar Articles for the Week of July 15

, discusses how biosimilars can be part of a strategy for delivering high-quality care while achieving savings.

 Patients with HER2-positive breast cancer treated with the biosimilar 

 experienced similar adverse events and well-being as those treated with the originator drug (Herceptin), according to a study using a smartphone app to track symptoms.

biosimilar disease-modifying antirheumatic drugs (DMARDs)

 suggest cost-effectiveness for patients with rheumatoid arthritis (RA) who did not respond well to methotrexate, potentially improving patient outcomes and health care affordability.

 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.

challenges with pharmacy benefit managers (PBMs)

 that plague the biosimilar industry and new legislation that attempts to reform their practices and encourage biosimilar adoption.

Here are the top 5 biosimilar articles for the week of July 15, 2024.

The cost-effectiveness demonstrated in the study can help health care stakeholders, rheumatologists, and patients better understand the benefits and financial feasibility of biosimilar DMARDs. | Image Credit: MicroOne - stock.adobe.com

For patients with rheumatoid arthritis (RA) who did not respond well to methotrexate, a study in 

 found that biosimilar drugs were both more beneficial and more cost-effective than leflunomide.

Current clinical guidelines for treating patients with RA typically recommend methotrexate monotherapy. However, over 50% of the patient population experiences failed treatment with methotrexate based on an inadequate response. If failed treatment occurs, it is recommended to use multiple conventional synthetic disease-modifying antirheumatic drugs (DMARDs), like leflunomide, combined with methotrexate. The next line of therapy combines biological DMARDs with methotrexate.

Expensive drug costs are the main reason biological DMARDs are not used as often in practice. A cross-sectional survey in Hong Kong found the high cost of biologics remains a major barrier to the first attempt of these drugs and long-term adherence to them.

 Even in countries when insurance covered up to 90% of biological DMARD costs, drug adherence was still not improved because of personal expenses and an increase in prescriptions.

More recent, Hong Kong has experienced price reductions ranging from 54% to 87% for CT-P13 (biosimilar infliximab) and ABP-501 (biosimilar adalimumab) compared with their reference products.

 The price reductions may help patients more easily access biological DMARDs after methotrexate failure.

The economic evaluation was initiated by the University of Hong Kong/Hospital Authority Hong Kong West Cluster. Data were recorded using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) reporting guideline. Disease activity was measured in quality-adjusted life-years (QALYs).

There were 25,099 patients with RA who participated in the study at an average age of 56 years old. More than half of the patient population identified as women (72.7%). Treatment with biosimilar DMARDs was cheaper and led to better outcomes (higher QALYs) than treatment with leflunomide.

The breakdown of the costs and QALYs were:

* Leflunomide: lifetime health care cost of $154,632 and 14.82 QALYs

* Biosimilar infliximab: $152,326 and 15.35 QALYs

* Biosimilar adalimumab: $145,419 and 15.55 QALYs

While biosimilar infliximab was slightly cheaper than leflunomide, biosimilar adalimumab was both cheaper and led to slightly better outcomes.

In the deterministic sensitivity analysis, the incremental cost-effectiveness ratio (ICER) (US$/QALY) was −$9088 to $10,238 when comparing biosimilar infliximab with leflunomide. Biosimilar adalimumab compared with leflunomide resulted in a range from −$15,797 to −$8615.

The probabilistic sensitivity analysis showed the probability of treatment sequences initiated with leflunomide, biosimilar infliximab, and biosmilar adalimumab being cost-effective out of 10,000 iterations was 0%, 9%, and 91%, respectively.

From a global perspective, 41 countries were identified with recorded sales of biosimilar infliximab in July 2022 from the IQVIA-MIDAS database. Research found 15 of the 28 high-income countries, similar to Hong Kong’s economic development, had lower unit prices of biosimilar infliximab.

In Australia, a study found etanercept experienced a 40% decrease in price for both the originator and biosimilar once the market listed the biosimilar.

 Prior to launch, etanercept was priced at US$1068 for a 50 mg/L 4 x 1 mL pen device but afterwards the drug was priced about US$641. Ultimately, Australia saw an average of $6 million in cost savings because of the biosimilar launch.

Study limitations included the treatment efficacies that were largely retrieved from independent randomized controlled trials with heterogeneity in patients’ demographic and clinical profiles.

 Additionally, participants were naive to biological DMARDs or had only experienced 1 biological DMARD prior to enrollment. Treatment efficacy may have been overestimated after applying Health Assessment Questionnaire Disability Index improvements to the cohort.

The cost-effectiveness demonstrated in the study can help health care stakeholders, rheumatologists, and patients better understand the benefits and financial feasibility of biosimilar DMARDs.

1. Peng K, Chan SCW, Wang Y, et al. Cost-effectiveness of biosimilars vs leflunomide in patients with rheumatoid arthritis. 

. 2024;7(6):e2418800. doi:10.1001/jamanetworkopen.2024.18800

2. Li Y, Lau LKW, Peng K, et al. Factors influencing choice of b/ts DMARDs in managing inflammatory arthritis from a patient perspective: a systematic review of global evidence and a patient-based survey from Hong Kong. 

. 2023;13(10):e069681. doi:10.1136/bmjopen-2022-069681

3. Santoro C. Biosimilar etanercept similar to Enbrel in persistence of treatment, cost savings for patients with RA. The Center for Biosimilars

. February 6, 2024. Accessed July 10, 2024. 

https://www.centerforbiosimilars.com/view/biosimilar-etanercept-similar-to-enbrel-in-persistence-of-treatment-cost-savings-for-patients-with-ra

Economic evaluations of biosimilar disease-modifying antirheumatic drugs (DMARDs) suggest cost-effectiveness for patients with rheumatoid arthritis (RA) who did not respond well to methotrexate, potentially improving patient outcomes and health care affordability.

Biosimilar DMARDs Offer Cost-Effective Option for Patients With RA After Failed Methotrexate Treatment

Jeffrey Casberg

Jeffrey Casberg, MS, RPh, senior vice president of pharmacy at 

, discussed the FDA approvals of new drugs and what these new launches could mean for drug pricing. He also spoke to the approach pharmacy and therapeutics committees take to reviewing new pipeline drugs.

What is your reaction to the FDA approval of the first denosumab biosimilars?

So denosumab biosimilars, there was 2 approved; 

Wyost [denosumab-bbdz] and Jubbonti [GP2411]

. The Jubbonti is for Prolia, the Wyost is for Xgeva. One is more oncology based, one is more osteoporosis based.

They were approved, but there's no announcement on when they're going to be launched. We're thinking they might even be delayed in launch till 2025. 

With only one manufacturer coming out, Sandoz, with both of those, we'll get some discount on the brand and reference drug but it's not going to be significant. It's not going to be like the 

Humira [adalimumab] situation with 9 or 10 biosimilars.

What are your thoughts on what the launch of the first tocilizumab biosimilar means for patients with autoimmune conditions?

 is actually IV [intravenous] and sub-q [subcutaneous]. I think that the 2 products launched, 

 is both IV and sub-q, and that's from Fresenius Kabi.

For the most part, Actemra is used in rheumatoid arthritis, a couple other conditions as well. Getting biosimilars in a different therapeutic area, including Actemra, that will be a big advancement. That's 2 biosimilars, so we will get a little competition there on pricing, but I don't know if I can predict what the discounts will be—maybe, 20% to 30% off.

How are pharmacy and therapeutics committees likely to approach new pipeline drugs, considering factors like efficacy, safety data, and potential cost compared to existing options?

P&T [pharmacy and therapeutic] committees are pretty standard in their approach on how they review drugs for formulary inclusion. It really comes down to safety, cost, and efficacy.

I think in today's world, the only difference is that there's a lot of these new orphan drugs which don't have a lot of competitors, so the P&T committees have to look at a drug on its own or a small number of patients, so they really look at the efficacy opportunity—which patients should get the drug, and what the criteria can be.

It's a lot less managing 4 or 5 drugs in a therapeutic area and comparing the pros and cons of drugs that are very similar. Nowadays, we're comparing a million-dollar drug which has no competition and who the patient should be and what the criteria should be. So there is a little shift in reviewing drugs from multiple drugs in 1 therapeutic class to orphan drugs.

Jeffrey Casberg, MS, RPh, senior vice president of pharmacy at IPD Analytics, highlights new FDA approvals, the launch of the first tocilizumab biosimilar, and how pharmacy and therapeutics committees approach new pipeline drugs.

IPD Analytics' Jeffrey Casberg Discusses Recent Biosimilar Approvals

The Top 5 Biosimilar Articles for the Week of July 8

As the weather heats up for the US and Europe, so too did the 

, with clinical trial results from conferences and a study showcasing how to overcome economic and noneconomic barriers to oncology biosimilars.

 As Celltrion publishes phase 3 data on its tocilizumab biosimilar, other companies finalize partnerships, and Formycon 

 to receive approval for the American market. It was also approved with interchangeability.

FDA has approved Ahzantive (aflibercept-mrbb)

 as the third biosimilar referencing Eylea (aflibercept) for the treatment of eye conditions, including age-related macular degeneration.

 to remove switching study data for companies seeking to obtain an interchangeability designation for their biosimilars.

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

Recent data has utilized enhanced assessment of electronic patient-reported outcomes (ePROs) to identify undetected symptoms while improving symptom management for patients with various cancer subtypes. | Image Credit: Maksym - stock.adobe.com

Patients with HER2-positive breast cancer who were treated with biosimilar trastuzumab-dkst (Ogivri) experienced equivalent symptoms, adverse events (AEs), and well-being as patients treated with the originator trastuzumab (Herceptin), according to the results of a study published in 

Oncology care has benefitted significantly from biosimilars and their reference products, and these agents account for approximately 70% of the growth in costs of drugs from 2010 to 2015. Biosimilars are one way to reduce costs without affecting quality of care.

The study provided an enhanced assessment of electronic patient-reported outcomes (ePROs) that identified undetected symptoms while improving symptom management for patients with various cancer subtypes. The system has suggested improvements in well-being and awareness of AEs between outpatient visits.

The ePRO application collects patient-reported information in clinical trials, including symptoms, quality of life, treatment adherence, and treatment satisfaction. Data is accurately reported in real time and offers informed decisions when analyzing the efficacy and safety of medical interventions. The technological application allows patients to report their treatment results without the limitations of paper-based methods, with valuable insights delivered more efficiently and accurately.

There is limited research on the real-world outcomes, tolerability, and quality of life that has been performed using ePRO data collected from patients treated with anti-HER2 biosimilars.

An observational study was conducted to investigate the daily functional activity, symptoms, and therapy AEs recorded with medidux smartphone application in patients undergoing trastuzumab-dkst therapy.

In December 2017, trastuzumab-dkst was approved by the FDA as the first trastuzumab biosimilar for treatment of HER2-overexpressing breast or metastatic stomach cancer.

 Some patients experienced AEs such as fever, nausea, vomiting, infusion reactions, diarrhea, infections, increased cough, headache, fatigue, shortness of breath, rash, low white and red blood cell counts, and muscle pain.

Over a 20-month duration, a noninterventional, multicenter, prospective, observational study was held across 5 study sites in Switzerland.

The study enrolled patients who received an anti-HER2 treatment regimen. This regimen included an initial intravenous dose of trastuzumab-dkst at 8 mg/kg body weight, followed by maintenance doses of 6 mg/kg. The treatment could be given with or without pertuzumab, chemotherapy, and/or hormone therapy, depending on whether it was administered in a neoadjuvant (pre-surgery) or palliative (symptom management) setting.

The medidux app is a patient-centered, therapy assistance application that supports the structured, standardized, and dynamic documentation of symptoms and therapy AEs. Patients received the app and were instructed to record their symptoms, well-being, EQ-5D-5L questionnaires, cognitive capabilities, and vital parameters every day. Regular study visits were scheduled on days 1, 21, and 42 during 3 weekly chemotherapeutic interventions.

Each patient had an observational period that lasted 6 weeks and at the end, patients decided whether to continue therapy with trastuzumab-dkst or the originator trastuzumab.

The study had a primary objective to evaluate ePRO data received in the medidux app by patients with HER2-positive breast cancer treated with trastuzumab-dkst while comparing the data with ePRO findings obtained from a historical cohort treated with trastuzumab in 2 previous studies (

The well-being of patients in both cohorts and the electronically reported symptoms was considered the secondary objective.

A total of 53 patients who identify as female were enrolled in the study with an average age of 57 years in the prospective cohort and 51 in the historical cohort. Around 38.9% of patients had tumor stage 2 with fewer patients (22.2%) had palliative treatment than neoadjuvant or adjuvant treatment. Over half of the population received dual anti-HER2 blockade with trastuzumab and pertuzumab (59.3%).

Patients in the prospective cohort experienced 84 of the 92 available different symptoms entered in the app, with the average being more than 4 symptoms a day, that resulted in a total of 9680 symptoms.

There were 54 of the 82 different symptoms found in the historical cohort, with the average being more than 3 symptoms a day, that resulted in 6904 symptom entries.

Common symptoms included fatigue, taste disorder, nausea, diarrhea, dry mucosa, joint discomfort, tingling, sleep disorder, headache, and appetite loss. Most patients in the trastuzumab-dkst cohort experienced minimal (grade 0) and mild (grade 1) toxicities, followed by grade 2, 3, and 4 toxicities.

Common Terminology Criteria for Adverse Events (CTCAE) Score

The primary end point was evaluated among 50 patients who received trastuzumab-dkst and 38 patients treated with the originator trastuzumab.

The average CTCAE scores could be compared between the 2 cohorts with an estimated difference of –1.27 (95% CI, –7.24 to 4.70; 

 = .68). Notably, the adjusted average of CTCAE scores were not altered between cohorts either (2.51; 95% CI, –3.27 to 8.29).

Secondary end points were analyzed in 52 patients who received trastuzumab-dkst and 38 patients as part of the historical cohort. On average, the difference in well-being patients treated with trastuzumab-dkst and originator trastuzumab was 4.45 (95% CI, –3.53 to 12.44; 

 = .28). There were no major differences between the adjusted well-being scores (3.78; 95% CI, –4.64 to 12.19) of both groups.

Cognitive Abilities in the Prospective Cohort

Data from 37 patients (70%) who performed at least 1 cognitive test were involved in the analysis, with 767 cognitive tests entered overall. The average execution time was 42.9 seconds. However, the small sample size and limited number of cognitive tests recorded were not correlated to the cognitive abilities and treatment performed.

The study design limited the results because it neglected a prospective control group and could not be randomized. Additionally, the app was not skilled to perform questionnaires to patients and cognitive abilities were not available for the historical cohort.

Future studies are necessary to analyze data through a randomized design with real-world functions in patients with HER2-positive breast cancer who were treated with anti-HER2 biosimilars.

Ultimately, treatments of both trastuzumab-dkst and the originator expressed equal symptoms, AEs, and well-being as reported by ePRO. Results highlighted the integration of an ePRO tool into research and clinical practice can provide reliable information when investigating tolerability and safety outcomes of similar therapeutic compounds.

1. Trojan A, Roth S, Atassi Z, et al. Comparison of the real-world reporting of symptoms and well-being for the HER2-directed trastuzumab biosimilar ogivri with registry data for herceptin in the treatment of breast cancer: Prospective observational study (OGIPRO) of electronic patient-reported outcomes. 

2. The ultimate guide to ePRO: Everything you need to know. Lindus Health. Accessed July 1, 2024. 

https://www.lindushealth.com/blog/the-ultimate-guide-to-epro#:~:text=Defining%20ePRO%3A%20What%20It%20Is%20and%20Its%20Importance&text=In%20simple%20terms%2C%20ePRO%20involves

3. FDA approves Ogivri as a biosimilar to Herceptin. News release. FDA. December 1, 2017. Accessed July 2, 2024. 

https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-ogivri-biosimilar-herceptin#:~:text=On%20December%201%2C%202017%2C%20the,gastric%20or%20gastroesophageal%20junction%20adenocarcinoma).

4. OGIVRI (trastuzumab-dkst). Ogivri. Accessed July 2, 2024. 

Patients with HER2-positive breast cancer treated with the biosimilar trastuzumab-dkst experienced similar adverse events and well-being as those treated with the originator drug (Herceptin), according to a study using a smartphone app to track symptoms.