Tony Hagen is senior managing editor for The Center for Biosimilars

A phase 3 study of a trastuzumab biosimilar candidate (TX05) and reference product (Herceptin) has demonstrated equivalence in patients with human epidermal growth factor receptor 2 (HER2)-positive early stage breast cancer, according to findings presented at the European Society for Medical Oncology Congress 2021.

The trial enrolled patients (N = 809) in the neoadjuvant, or presurgery, setting. Of those, 674 were evaluable. The primary end point was therapeutic equivalence based on pathologic complete response (pCR), or absence of residual cancer, following neoadjuvant chemotherapy.

Secondary end points were objective response rate (ORR), immunogenicity, safety, and tolerability.

Patients were recruited at 124 treatment centers in 10 countries, including Russia, Hungary, Chile, and India. They received four 3-week cycles of epirubicin and cyclophosphamide and were then randomized to four 3-week cycles of paclitaxel and TX05 or the reference biosimilar (TRA, as available in the European Union). Investigators said close to 100% of patients completed all planned cycles of trastuzumab therapy.

They said the proportions of patients meeting pCR criteria for equivalence were “highly similar” between the TX05 (48.8%) and TRA (45.3%) cohorts (risk ratio, 1.0783).

They also said equivalence was observed when patients from both cohorts were stratified according to cancer stage and Eastern Cooperative Oncology Group (ECOG) performance status. ECOG is a means of classifying patients according to the level of disability they suffer as a result of their cancer, with zero representing the highest functionality.

ORR was also highly similar between the TX05 (84.3%) and TRA (85.0%) groups, and findings for patients with complete response, partial response, and stable disease were also highly similar between cohorts. The same was true for pharmacodynamics, authors of the study said.

“In all sensitivity analyses, including a 'tipping point' analysis, the 95% CI of the risk ratio was completely contained within the predefined interval,” they wrote.

Safety analysis of treatment-emergent adverse events (TEAEs) was confined to cycles 5 through 8 of the treatment, as this was the period during which patients received trastuzumab. The investigators said 62.4% of patients experienced TEAEs with TX05 vs 62.5% of patients with TRA, which they said was similar and demonstrative of biosimilarity for TX05.

The most common TEAEs were musculoskeletal and connective tissue disorders, nervous system and gastrointestinal disorders, general disorders, and investigative-related and administration-site conditions.

“Overall, the TX05 study treatment was well tolerated. The safety profile was consistent with the known profile of TRA with no significant safety findings seen in the study,” the authors wrote.

“The results of this study support that there is no clinically meaningful difference between TX05 and [TRA],” they said, adding that based on pharmacokinetic similarity, it was possible to conclude that TX05 is also highly similar to the US version of reference trastuzumab.

The study was sponsored by Tanvex BioPharma USA, which is the company developing TX05 for market.

Preliminary results from the phase 3 study concerning just pCR were released in February 2021.

Krivorotko P, Manikhas A, Moiseenko F, et al. Trial comparing the safety, efficacy, and immunogenicity of trastuzumab biosimilar candidate (TX05) with originator trastuzumab in HER2+ early breast cancer. Presented at ESMO Congress 2021; September 17-21, 2021. ePoster 127P.

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Investigators said TX05 met pathologic complete response criteria for equivalence to the originator product, Herceptin. The biosimilar candidate also fell within objective response rate, immunogenicity, safety, and tolerability margins for similarity. 

Tanvex Presents Positive Findings for Trastuzumab Candidate at ESMO

A phase 3 study of the bevacizumab biosimilar BCD-021 vs reference bevacizumab (Avastin) in patients with stage IIIB or IV nonsquamous non–small cell lung cancer (NSCLC) demonstrated equivalence, investigators reported at the European Society for Medical Oncology (ESMO) Congress 2021.

Investigators sought to elucidate the efficacy, safety, pharmacokinetics (PK), and immunogenicity of BCD-021 compared with reference bevacizumab.

BCD-021 was approved as a biosimilar in November 2015 by the Russian Ministry of Health. The drug was developed by Russian biotechnology company Biocad. The originator was developed by Genentech and Roche.

Patients (n = 357) from Russia and India were randomized 1:1 and 2:1, respectively, to either biosimilar or reference bevacizumab plus paclitaxel and carboplatin once every 3 weeks for 6 cycles. At week 18, patients with stable disease or complete or partial response (CR/PR) were offered the opportunity to continue with BCD-021 until disease progression, death, or intolerable toxicity.

The primary end point was objective response rate (ORR) as measured by response at week 19 and confirmed 4 weeks later. The primary PK end point was variation of drug concentration, as measured by C

, or peak concentration following dosing.

Additional end points were safety and immunogenicity.

Investigators said the treated population measured 341 patients (BCD-021, n = 205; BEV, n = 136). Confirmed ORRs were observed in 34.6% of the biosimilar cohort (n = 71) and 33.8% of the reference population (n = 46). The respective confirmed percentages for CR were 1.5% and 0.7%; and PR, 33.2% and 33.1%.

Patients experiencing stable disease in the biosimilar and reference groups were 31.7% and 33.8%, respectively. The proportions experiencing progressive disease were 13.2% and 11.0%, respectively.

Investigators said criteria were met for PK equivalence in both the Indian and non-Indian populations.

Patients experiencing any adverse event (AE) were 91.3% in the biosimilar group vs 93.4% in the originator cohort; serious AEs were 13.6% vs 10.9%, respectively; and treatment-related serious AEs were 3.4% vs 2.2%.

Patients discontinuing due to AEs were 4 and 2 in the biosimilar and reference groups, respectively; and deaths were 14 and 8, respectively.

The most frequent AEs were anemia, neutropenia, and alopecia.

“This study demonstrated equivalence between BCD-021 and (Avastin) in terms of ORR risk difference and risk ratio. PK equivalence of BCD-021 and [Avastin] was also confirmed. Safety and immunogenicity parameters were comparable” between the biosimilar and reference agents, investigators concluded.

Fadeeva N, Roy B, Nagarkar R, et al. A phase III study comparing BCD-021, a bevacizumab biosimilar, and reference bevacizumab in patients with stage IIIB or IV non-squamous NSCLC. Presented at: ESMO Congress 2021; September 16-21, 2021. ePoster 1338P.

BCD-021 demonstrated equivalence in a phase 3 study involving Russian and Indian patients with advanced non–small cell lung cancer (NSCLC). 

Biocad's BCD-021 Bevacizumab Biosimilar Demonstrates Equivalence in NSCLC

Investigators in China reported positive equivalence findings from a phase 3 trial of a bevacizumab biosimilar candidate (MIL60) and platinum-based chemotherapy as first-line treatment in Chinese patients with recurrent or advanced non–small cell lung cancer (NSCLC).

The findings, presented in poster form at the European Society for Medical Oncology (ESMO) Congress 2021, showed MIL60 is highly similar to the originator bevacizumab (Avastin) in terms of pharmacokinetics (PK), immunogenicity, and safety. MIL60 is a biosimilar candidate under development by Beijing Mabworks Biotech.

Patients with stage IV or recurrent NSCLC and no previous history of systemic antitumor therapy were randomized 1:1 to 6 cycles of 15-mg/kg intravenous MIL60 plus carboplatin/paclitaxel (n = 253, full analysis set [FAS]) or similar dosing of reference bevacizumab plus carboplatin/paclitaxel (n = 255, FAS).

Patients then received MIL60 maintenance therapy (7.5 mg/kg). This afforded further evaluation opportunity through longer exposure.

The primary end point was the 12-week objective response rate (ORR) assessed by independent review committee (IRC), and secondary end points included 18-week ORR, duration of response (DoR), disease control rate, progression-free survival (PFS), overall survival (OS), and safety.

The IRC-assessed FAS ORRs for the biosimilar and reference cohorts were 48.6% (95% CI, 42.6%-57.8%) and 43.1% (95% CI, 37.4%-52.1%), respectively. Investigators noted the ORR finding of 48.6% for the Chinese patient population was significantly higher than in Western patients previously studied (38%).

Investigators observed no significant differences in median DoR, PFS, or OS. Median OS was 19.3 months and was comparable to previous study findings.

No patients in either cohort achieved complete response. The partial response rate was 48.6% and 43.1% in the biosimilar and reference groups, respectively. Stable disease was achieved by 44.3% and 45.5%, respectively.

Investigators reported no significant difference between the study arms in the incidence of treatment-emergent adverse events (TEAEs). In the biosimilar and reference cohorts, grade 3 or higher TEAEs were 70.3% and 72.6%, respectively; serious adverse events were 28.1% and 28.6%, and treatment-related TEAEs were 78.9% and 81.1%.

PK parameters also were similar for patients with advanced or recurrent NSCLC.

Wang J, Wan R, Dong X, et al. Efficacy and safety of MIL60, a bevacizumab biosimilar, in combination with paclitaxel/carboplatin in the patients with advanced or recurrent non-squamous non-small cell lung cancer: a randomized, double-blind, multicenter phase 3 study. Presented at: ESMO Congress 2021; September 16-21, 2021. Poster 1339P.

MIL60 bevacizumab biosimilar candidate demonstrates equivalence to the originator Avastin in a population of Chinese patients with non–small cell lung cancer (NSCLC) treated in a frontline setting.

MIL60 Bevacizumab Biosimilar Candidate Demonstrates Equivalence in NSCLC

Samsung Bioepis reported results of what it called the longest follow-up study of patients with human epidermal growth factor receptor 2–positive early or locally advanced breast cancer treated with a trastuzumab biosimilar. The findings will be formally presented in poster form at the European Society for Medical Oncology (ESMO) Congress 2021. 

Investigators said 5-year event-free survival rates in the phase 3 study were 82.8% in the biosimilar (Ontruzant) cohort and 79.7% in the reference trastuzumab (Herceptin) group.

Five-year overall survival rates were 93.1% and 86.7% for the biosimilar (HR 0.62; 95% CI, 0.32-1.22; 

 = .17) and originator drug cohorts, respectively.

Investigators reported 3 cases of asymptomatic significant left ventricular ejection fraction (LVEF) decrease (Ontruzant, n = 1). Each of these patients recovered with LVEF ≥ 50%. There were no cases of symptomatic congestive heart failure or cardiac death in either cohort.

Events of recurrence, progression and death were reported for 17.2% of patients in the biosimilar group (HR 0.78; 95% CI, 0.48-1.25; 

Patients in the biosimilar cohort (n = 186) and the reference group (n = 181) received 8 cycles of trastuzumab concurrently with chemotherapy in the neoadjuvant setting. After surgery, they received 10 cycles of trastuzumab over 1 year. Median follow-up duration was 68 months from the point of randomization.

The positive findings for the trastuzumab biosimilar Ontruzant in patients with human epidermal growth factor receptor 2 (HER2)–positive early or locally advanced breast cancer were presented at the European Society for Medical Oncology (ESMO) Congress 2021.

Samsung Bioepis Reports Long-term Ontruzant Findings for HER2-Positive Breast Cancer

Using data from a study (N = 220) of the infliximab biosimilar CT-P13 in patients with Crohn disease, investigators said they have improved understanding of the clearance of infliximab and its predictive value for the development of antidrug antibodies (ADA).

Investigators found that initial infliximab clearance, concomitant use of immunomodulators, and infliximab dosage were statistically significant predictors of the time to development of ADAs.

Investigators reported that the risk for ADA increases 61% for every increase of 0.1 L/day in drug clearance; however, it decreases by 41% if immunomodulators are administered concomitantly, and it also decreases 29% with every increase in dosage of 100 mg.

They calculated that for a patient with infliximab clearance of 0.2 L/day who is not taking immunomodulators and has an infliximab dose of 328 mg, the average time to first ADA would be 374 days.

With higher clearance of 0.4 L/day, also with dosage of 328 mg and no immunomodulators, the ADA onset would occur in 144.5 days.

A higher starting infliximab dose of 428 mg would lengthen the time to onset to 203 days, and adding immunomodulator treatment would extend time to ADA onset to 354 days, they said.

“Our results suggest that early assessment of clearance should guide treatment optimization with infliximab in patients with Crohn disease, including the addition of concomitant immunosuppressants or increasing the dose during induction,” authors of the study concluded.

Kutschera M, Primas C, Reinish S, et al. Initial clearance of infliximab is a predictor for the time of formation of anti-drug antibodies. Presented at: ECCO’21 Congress; July 2-3 and 8-10, 2021. Poster DOP74

Congress of the European Crohn's and Colitis Organisation

Concomitant use of immunomodulators and dosage are important variables in the development of antidrug antibodies (ADAs) for patients receiving infliximab for Crohn disease, investigators report. 

Investigators Elucidate ADA Predictive Value of Infliximab Clearance in Crohn Disease

Analyses of multiple switches between biosimilars and originator forms of infliximab were presented at the European Crohn’s and Colitis Organization annual meeting  (ECCO’21).

Switching Between Remicade and Biosimilars

Patients with inflammatory bowel disease (IBD) who switched multiple times between biosimilar forms of infliximab and the originator product (Remicade) demonstrated no unusual patterns in efficacy, safety, or immunogenicity, investigators reported at ECCO’21.

Investigators sought to elucidate outcomes of significance among patients who switched from biosimilars to the reference product and switched multiple times between biosimilars. “As the access to biosimilars at competitive prices increases, it is necessary to evaluate multiple switches to provide data on their interchangeability,” they wrote.

In this retrospective cohort study (N = 26), investigators evaluated clinical disease activity, biochemical markers, infliximab trough (lowest concentration) levels, and anti-infliximab antibody levels both before and after switching.

The study enrolled patients with Crohn disease (n = 22) and ulcerative colitis (n = 4). Most patients were between 17 and 42 years of age, had ileocolonic disease, and an inflammatory phenotype (nonstricturing/nonpenetrating, structuring, or penetrating). Investigators said 44% of patients had perianal disease and half had pancolitis.

They said 51% of patients had prior resection surgery and 27% were on combination therapy when they first switched among infliximab products. Nine patients (35%) switched 3 times.

Investigators said there was no significant difference in the percentage of patients in clinical remission and no significant differences in laboratory markers such as C-reactive protein (an inflammation marker), hemoglobin (anemia marker), or albumin (protein deficiency marker) were noted before or after multiswitching.

Mean drug trough levels were not significantly different and no patients developed antidrug antibodies, had infusion-related adverse events, or lost response leading to drug discontinuation. Investigators said drug persistence was 100%.

Investigators found that patients who switched from one infliximab biosimilar to another experienced an increase in drug trough levels following the switch, although there was no effect on clinical and biochemical disease activity.

In a poster presentation at ECCO’21, researchers concluded that switching infliximab biosimilars in IBD “appears safe in the short term with respect to maintaining drug pharmacokinetic (PK) profile and disease control whether switching for the first or second time.”

The advent of anti–tumor necrosis factor (TNF) biosimilars, which reduce inflammation, has enabled switching from originator products and cost savings in IBD without loss of disease control. In this study, investigators set out to understand the significance of a switch between biosimilars.

They reported on a prospective study (N = 221) of patients who switched from Remsima to Flixabi, both infliximab biosimilars, produced by Celltrion and Samsung Bioepis, respectively. Outcomes were compared for patients who switched up to 2 times.

Patients were stable on infliximab at baseline, and 79% (n = 174) were on concomitant immunomodulators. Investigators said roughly half of patients (n = 112) had a PK analysis done before and after switching.

Investigators observed a baseline median trough level of 4.5 µg/mL (2.9-6.3) prior to switching and 5.1 µg/mL (3.4-7.0; 

Clinical scores, including for C-reactive protein, trough infliximab levels, and clinical disease activity, were similar before and after switching, and no new anti-infliximab antibodies were observed.

Investigators said 107 patients (48%) switched infliximab biosimilars for the second time, and of those, PK analysis was performed for 51. Investigators said the post-switch increase in median drug trough levels was similar between patients who switched for the first (4.7 vs 6.1 µg/mL, 

They said there was no change in clinical disease activity or C-reactive protein in either group. Further, the use of concomitant immunomodulators and patient disease classification had no bearing on changes in infliximab levels, although these findings were not statistically significant (

1. Nascimento C, Revés J, Morão B, et al. Outcomes of multiswitching from original infliximab to biosimilars in patients with inflammatory bowel disease. Presented at: ECCO’21 Congress; July 2-3 and 8-10, 2021. Poster P555.

2. Luber R, O’Neill R, Singh S, Arkir Z, Irving P. Switching infliximab biosimilar: no adverse impact on inflammatory bowel disease control or drug levels with the first or second switch. Presented at: ECCO’21 Congress; July 2-3 and 8-10, 2021. Poster P485.

Pharmacokinetic, safety, and efficacy findings for patients with inflammatory bowel disease (IBD) were presented at the European Crohn's and Colitis Organization's annual meeting. 

Investigators Report Findings on Infliximab Switching in IBD

Health care consumers are routinely blitzed with advertisements by drug companies, so how are they to find out about biosimilars? And further, providers and payers aren’t necessarily going to agree on what drugs should be prescribed to patients. Should they be lowest-cost or should the manufacturer with the most reliable supply chain be granted preference on formulary?

A panel of industry experts moderated by an economist addressed these issues in a recent talk at the American Conference Institute’s 2021 Summit on Biosimilars and Innovator Biologics.

Interchangeability almost has become an unnecessary stumbling block to implementation of biologics and biosimilars

“The thing that sometimes is indicative of our market is that with so many different stakeholders, incentives are not always aligned,” said Ali Ahmed, senior vice president of biosimilars at Fresenius Kabi.

He joined panelists Terry Rea, vice chair of the Intellectual Property Group at Crowell & Moring in Washington, DC, and Sonia T. Oskouei, vice president of biosimilars at Cardinal Health, in the discussion conducted by Joseph P. Fuhr, professor emeritus of economics at Widener University.

“I’m afraid that consumers are overwhelmed with anecdotes on biosimilars. I mean, we advertise to them directly. We have insurance companies that advertise constantly on TV,” Rea said. The world was a lot simpler years ago, but things have gotten more specialized, and with that, complexity has crept in. “Our complex system is delaying getting good medications to patients.”

Kaiser Permanente is a managed care consortium that has had tremendous success in getting biosimilars into use by patients, but it’s the integrated nature of that network that has been key to this accomplishment, Ahmed said. “It’s not that I’m advocating for full integration of every health plan with a network, but it does show the power of aligning incentives.”

Six years after biosimilars first appeared in the United States, a new level of complexity is about to surface with the pending arrival of biosimilars designated as “interchangeable,” which would enable pharmacists to dispense them in place of originator biologics without a prescriber’s express authorization.

Panelists said the interchangeable designation has already added new wrinkles to biosimilar adoption. Manufacturers may not see any value in seeking interchangeable designations for their biosimilars, and they may not even qualify. The FDA requires studies to demonstrate no changes in outcomes for patients who switch multiple times between originator and biosimilar agents.

“Some of these products could be waiting a lifetime and not have that designation, and there continues to be a knowledge gap around what the designation means and the implications of it,” Oskouei said.

The first interchangeable insulin biosimilars are expected to be approved soon, and this will be an opportunity to observe how the interchangeable designation functions, particularly in the managed care setting, Oskouei said.

“If there’s ever an opportunity to bring more affordable medicine to diabetes care in the United States, this is a great, great event,” she said.

You can see good uptake of biosimilars in oncology, but the same is not true across the board, Ahmed said. “I’m not sure whether spending all that extra time doing the clinical trials to get that interchangeable designation is really worth the squeeze. It will really depend on product.

“Maybe in the autoimmune space there could be more value to it, although you could still argue that working closely with a pharmacy benefit manager and a payer to get a preferred formulary position would be actually more valuable than having an interchangeable designation,” he said.

I do think that the number of patents that protect some of these molecules extends the patent term, or the time of a period of exclusivity, far beyond anything that was expected in the beginning

Still, an interchangeable designation may mean less to a provider who is trained to consider the clinical evidence supporting a treatment and base medical decisions on that. As a manufacturer, “You might be better off investing in health economic data. You know, how many times does a patient have to return to the hospital or the clinic?” Ahmed said.

“Interchangeability almost has become an unnecessary stumbling block to implementation of biologics and biosimilars,” Rea said. “It’s actually misleading and frustrating.”

Interchangeability is not likely to cause payers to put more emphasis on use of biosimilars, Ahmed said, speaking from the manufacturer’s point of view. “I think adoption and pricing and manufacturing capabilities and who you are in the market in terms of having a sales force that can pull that drug through the channel” will be more important to whether a payer grants preferred access or, simply, formulary access, he said.

A real barrier to biosimilar use is the patent portfolios that originator companies acquire to protect their product exclusivity, Rea said.

“I’m primarily a patent attorney, and I’d like to see manufacturers or the innovators be limited with the number of patents or the patents they’d like to assert [in litigation], because right now I do think we are delaying the number of biosimilars that are on the market, or preventing companies from even getting into that space, because of the huge number of patents,” she said.

“I do think that the number of patents that protect some of these molecules extends the patent term or the time of a period of exclusivity, far beyond anything that was expected in the beginning,” she said.

American Conference Institute: Summit on Biosimilars & Innovator Biologics

Panelists at the American Conference Institute's 2021 meeting took on the complexities of biosimilar adoption in a wide-ranging discussion.  

ACI Panelists Discuss Misaligned Incentives in the Biosimilars Market

Studies of adalimumab biosimilars in the European Union and the United Kingdom evaluated comparability and patient acceptance following a switch from the originator product (Humira).

In a study of patients with inflammatory bowel disease who switched to an adalimumab biosimilar (SB5, Hadlima) after achieving stability on Humira, investigators concluded adalimumab trough levels were comparable at up to 1-year post-switch.

Trough levels describe the lowest concentration of drug prior to repeat dosing. “Adalimumab trough levels remain within the therapeutic range after switch from originator to [Hadlima],” authors of the study wrote.

Also, the proportion of patients with secondary loss of response (SLOR), or who lost response to the drug during maintenance treatment, was comparable to reported data for the originator drug. No changes in disease activity were observed for patients on Hadlima, based on disease activity scores and biochemical parameters.

The study, conducted in Belgium, enrolled 110 patients with Crohn disease (n = 84) and ulcerative colitis (n = 26). At 12 months from baseline, Hadlima treatment was discontinued in 5 patients because of high adalimumab antidrug antibodies. Investigators said 9 patients presented with SLOR, 3 of whom discontinued treatment.

Mean trough levels for Hadlima were 9.21 μg/mL at baseline, 9.16 μg/mL at week 8 (

Deprez N, De Somer T, Baert d, et al. Evaluation of trough level and disease activity after switch from adalimumab originator to biosimilar in patients with inflammatory bowel disease. Presented at: ECCO’21 Congress; July 2-3 and 8-10, 2021. Poster 281.

Patients with inflammatory bowel disease (N = 110) were gauged according to their acceptance of a switch to an adalimumab biosimilar (SB5, Hadlima) after achieving disease stability on the originator product (Humira). Investigators reported an acceptance-of-switch rate of 79.3%.

The switch was optional and patient satisfaction was assessed at baseline and at 8 weeks, 6 months, and 1-year post-switch.

The most common reasons given for refusal to switch were fear of a disease flare (n = 8), ease for staying on the originator drug (n = 4), and lack of trust in biosimilars (n = 3). Patients who declined to switch numbered 15.

Investigators said no demographic factors were associated with a refusal to switch. At the end of the 1-year term, 28 patients had discontinued the biosimilar and the most common reasons given were high antidrug antibodies at baseline (n = 5), SLOR (n = 3), injection site pain (n = 8), and other adverse events not causally related to the biosimilar (n = 10).

Authors of the study reported that at the 1-year point, 74.5% of patients were still receiving treatment with the biosimilar.

Visual analogue scales (VAS), which are used to measure patient sentiment in cases where more reliable quantitative findings cannot be obtained, were used to measure local discomfort up to 30 minutes after injection. “The median VAS for local discomfort after 30 minutes was between 0 and 1/10 at all time points, which was not significantly different compared to the originator,” investigators wrote.

“Satisfaction with the decision to switch was high and remained stable over the different time points,” they wrote.

De Somer T, Deprez N, Deceuninck M, et al. Acceptance of switch, patient satisfaction and adverse events after switch from adalimumab originator to biosimilar SB5 in patients with inflammatory bowel disease in a real-life setting. Presented at: ECCO’21 Congress; July 2-3 and 8-10, 2021. Poster 469.

An interim analysis of the PROPER study of patients with Crohn disease who transitioned to an adalimumab biosimilar (SB5, Hadlima) following treatment with the reference product (Humira) demonstrated that most patients had no meaningful difference in disease activity or Hadlima dosing regimen by week 48 following transition to the biosimilar.

Investigators also concluded that the COVID-19 pandemic had no apparent effect on Hadlima use in this cohort (n = 459) and no new safety concerns were detected.

Investigators said 45 patients discontinued Hadlima and 10 withdrew from the study by week 48. Disease flare was reported for 29 (6.3%) patients, 7 of whom changed biologic treatment and 22 did not; 2 had SLOR.

Investigators said 12 patients reported 13 serious adverse events, of which 4 were considered related to use of the biosimilar (anal fistula, 2 perianal abscesses, and subileus).

Dignass A, Gisbert J, Freudensprung U, Addison J. The PROPER study: interim analysis of a pan-European real-world study of SB5 adalimumab biosimilar after transition from reference adalimumab in patients with Crohn’s disease. Presented at: ECCO’21 Congress; July 2-3 and 8-10, 2021. Poster 469.

Based on an ongoing crossover study enrolling patients with Crohn disease (N = 112) transitioning between Humira and the adalimumab biosimilar Imraldi, investigators concluded that despite limited knowledge and concerns about transitioning, patients generally accept the principals of biosimilars and can be reassured about receiving them.

The study is being conducted at University Hospital Southampton in the United Kingdom.

Among patients enrolled in the trial, investigators interviewed 35 on such topics as motivation to switch to a biosimilar, initial concerns, “reassuring factors,” and patient reflections on the experience.

Investigators noted that patients generally had little prior awareness of biosimilars but generally would accept a switch to biosimilar to minimize drug expense. “Prior to undertaking biosimilar transition away from the [originator brand], efficacy and adverse effects were common concerns for patients.”

Investigators reported that for patients to have confidence in biosimilars, they need to trust in their health care providers. They also stated that having a contact person on the health care team, education about biosimilars, and specific monitoring also provide reassurance.

“When reflecting on the experience, participants noted little subjective difference in efficacy or tolerability (although 22 participants specifically mentioned injection pain) following brand transition,” authors of the study wrote. “The majority feel comfortable with future transition to another adalimumab biosimilar.”

The investigators concluded that a tailored, patient-centered approach to using biosimilars is key to a successful switch.

Young D, Latter S, Harvey J, et al. IBD Reference and Biosimilar adalimumab CroSS over Study (iBaSS): a mixed methods clinical trial of patients transitioning between originator and biosimilar adalimumab. Qualitative findings from an interim analysis presenting the patient perspective. Presented at: ECCO’21 Congress; July 2-3 and 8-10, 2021. Poster 585.

Presentations at the European Crohn's and Colitis Organization annual meeting supported the transition to adalimumab biosimilars and provided patient acceptance data. 

Adalimumab Biosimilar Transition Studies Reported at ECCO'21 Congress

A study of British patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL) who were treated with the rituximab biosimilar Truxima vs the originator (Rituxan) demonstrated comparable efficacy and tolerability between therapies, according to a recent study.

Investigators analyzed data from 201 patients treated by 46 UK-registered hematologists and oncologists in this retrospective survey. They evaluated charts for adult patients who received the biosimilar or originator as first-line immunotherapy between January 1, 2018, and June 30, 2019.

The use of biosimilar rituximab yielded not only comparable outcomes but also average cost savings of $1385 per patient. “These findings should inform decision makers on the potential for cost reductions where the biosimilar [Truxima] is available as a treatment alternative,” the investigators said.

They noted high overall response rates (ORRs) and 6-month progression-free survival (96%-98%) across cohorts, as well as 1-year survival of 98% to 100% across cohorts.

ORRs for patients with CLL who received Truxima vs Rituxan were 97.9% and 93.9%, respectively. For patients with NHL, the respective ORRs were 94.0% and 95.9%.

Complete response (CR) rates for patients receiving the biosimilar vs originator were 64.6% and 67.3% for CLL and 68.0% and 73.5% for NHL, respectively. Partial response rates were 33.3% and 26.5% for CLL and 26.0% and 22.4% for NHL.

Treatment discontinuations due to progression, death, or initiation of a subsequent line of therapy were 12.8% and 12.2 % for patients with CLL receiving Truxima vs Rituxan and 12.2% and 10.4% for patients in the NHL cohorts, respectively.

The investigators said 54% to 66% of patients across cohorts did not experience grade ≥ 3 adverse events (AEs); the most common grade ≥ 3 AEs were neutropenia, fatigue, anemia, and infusion reactions.

They did note high health care resource utilization, including drug costs, diagnostic testing, office visits with oncologists, and hospital admissions.

McBride A, Daniel S, Driessen MT, et al. Real-world overall response rate and other outcomes related to originator and biosimilar rituximab in patients with chronic lymphocytic leukemia or non-Hodgkin’s lymphoma in the United Kingdom. Presented at: American Society of Clinical Oncology Annual Meeting; June 3-7, 2021. Abstract e18696.

Investigators reported high overall response rates and savings of roughly $1400 per patient across cohorts. 

Truxima Produces Savings and Comparable Outcomes for UK Patients With CLL, NHL

A model of rituximab use that involved transitioning a portion of patients to intravenous rituximab biosimilar (Truxima) from a subcutaneous originator rituximab (Rituxan) formulation demonstrated savings of $2359 to $8186 per patient with non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL), investigators reported at this year's American Society of Clinical Oncology meeting.

Truxima is a CD20-directed monoclonal antibody and was the first of 3 rituximab biosimilars approved in the United States.

Investigators based their savings analysis on a 5-million-member insured population (Medicare) in which 972 patients would be treated for NHL or CLL during a 1-year span. Of those patients, 49 would receive subcutaneous rituximab/hyaluronidase (SC-R). For purposes of the study, investigators assumed that 25% of the 49 patients (n = 13) would receive intravenous biosimilar treatment (IV-R-BIOSIM).

The 1-year model factored in drug and administration costs and assumed efficacy and safety would be equivalent between the 2 cohorts. For the IV-R-BIOSIM dosing, the investigators assumed body surface area of 1.8m

The objective was to project incremental cost differences between [IV Truxima] and [SC-Rituxan] over 1 year for a hypothetical 5-million-member US healthcare insured (Medicare) population.

They also assumed annual dose counts (with either IV-R-BIOSIM or SC-R) of 10 for untreated follicular lymphoma (FL) with maintenance; 8, untreated FL without maintenance, relapsed/refractory FL, or untreated diffuse large B-cell lymphoma; and 6, CLL. Duration of IV-R-BIOSIM infusion was assumed to be 3 hours. SC-R costs included an initial IV Rituxan dose.

For the 13 patients who received the hypothetical IV-R-BIOSIM dosing, estimated total 1-year savings were $57,864. The investigators said their budget impact model was most sensitive to low or high body surface area dosing and the proportion of patients with CLL.

“These findings demonstrate the potential economic benefits of IV-R-BIOSIM vs SC-R that may result in expanded access to rituximab therapy,” they said.

James E, Trautman H, McBride A, Choudhry A, Thompson S. US budget impact analysis of an intravenous rituximab biosimilar versus subcutaneous rituximab for the treatment of non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Presented at: ASCO 2021; June 3-7, 2021. Abstract e18821.

ASCO

Sizeable savings per patient with non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) were anticipated by a Medicare savings model. 

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