Tony Hagen is senior managing editor for The Center for Biosimilars

Recent attempts at reform across the biosimilar and generic drug landscape have not had unanimous support, legal experts noted at the American Conference Institute’s 11th Summit on Biosimilars & Innovator Biologics.

Last year, for example, California, enacted Assembly Bill (AB) 824, which enabled it to evaluate “pay for delay” settlements between biosimilar developers and reference product companies and bring enforcement actions for what it perceives as anticompetitive terms.

“That legislation is doing what the Supreme Court declined to do, which is impose a presumption that an agreement that includes certain terms has an anticompetitive effect,” said ACI panelist Karin Hessler, assistant general counsel for the Association for Accessible Medicines (AAM). The AAM has filed a series of court actions designed to overturn AB 824, but has thus far been

The AAM represents many large biosimilar developers and contends that California has improperly assumed the right to reject corporate settlements reached outside the state and also given itself leeway to impose excessive fines on individual companies (minimum of $20 million).

Another reason the pharmaceutical industry opposes this law is that it gives California the ability to review and evaluate all individual past settlements between drug companies, not just new settlements, said panelist David Korn, vice president of Intellectual Property and Law with the Pharmaceutical Research and Manufacturers of America.

If other states join in with regulations of their own, the operational environment for pharmaceutical companies could become far too restrictive, he said. “This should be left up to Congress, because if you have multiple state-based frameworks, it could create a patchwork [of laws] that would be harder to comply with.”

Hessler said there’s potential that patent settlements between companies will be “stifled” by this legislation. “If you have that sort of impact, then you may see generic and biosimilar companies not as frequently challenging patents, which ultimately could result in higher rather than lower drug prices,” she said.

In addition, California Governor Gavin Newsom has until the end of this month to sign or veto AB 852, a bill that would enable the state to contract for the manufacture of generic and biosimilar drugs. One of the driving thoughts behind this bill is that “there has to be a more viable pathway for producing an affordable insulin,” Hessler said.

The legal and pharmaceutical industries are watching this bill closely, the panel said.

“There are certainly provisions in the bill that talk about sales to California payers, but I think the assumption is that (drugs) would be distributed potentially nationally,” Hessler said.

Brand M, Korn D, Hessler K, Pearson M. Biosimilars state of the union: regulatory and legislative developments impacting the biopharmaceutical industry. Presented at: ACI 11th Summit on Biosimilars & Innovator Biologics; September 23, 2020.

Articles

ACI 11th Summit on Biosimilars & Innovator Biologics

Panelists at American Conference Institute's (ACI) 2020 virtual summit discuss California's legislative attempts to improve competition in the drug industry. 

California's Anticompetitive Legislation Is Scrutinized at ACI

Recent clinical and real world evidence for Samsung Bioepis biosimilars for bevacizumab and trastuzumab support use of these products in place of the reference versions, David Planchard, MD, and Mark D. Pegram, MD, said at the European Society for Medical Oncology Congress Virtual 2020, in a review of study findings.

“People may know that biosimilars save money overall, but want to see that the data prove clinical similarity in a very controlled setting as well as in the real world,” said David Planchard, MD, of Institut Gustave Roussy (IGR) in Villejuif, France. Planchard serves as associate professor of medicine with the Thoracic Tumor Board at IGR.

The Samsung Bioepis bevacizumab biosimilar Aybintio (SB8) was approved in August for marketing by the European Commission. Samsung Bioepis’ trastuzumab biosimilar Ontruzant was launched in the United States in April.

Planchard noted that SB8 and the bevacizumab reference product (Avastin, BEV) have an “identical primary amino acid sequence and have demonstrated highly similar structural, physiochemical and biological properties.” A phase 3 trial randomized 763 patients with non–small cell lung cancer roughly equally to SB8 and BEV.

 Of those, 258 completed induction treatment with SB8 and 277 with BEV. The mean age of patients was 60.2 vs 60 in the respective arms.

In the full analysis set (FAS), equivalence was demonstrated in terms of best overall response rate (ORR) risk ratio and risk difference. The ORR in the FAS was 47.6% for SB8 vs 42.8% for BEV. In the per protocol set (PPS), the best ORR was 50.1% for SB8 vs 44.8% for BEV.

Median progression-free survival (PFS) in the FAS was 8.5 months for SB8 vs 7.9 months for BEV, and in PPS the median PFS was 8.5 months vs 7.9 months, respectively. Median overall survival (OS) in the FAS was 14.9 months vs 15.8 months, respectively; and in PPS, 14.8 months vs 15.8 months. Mean duration of response was 6.38 months vs 6.79 months, respectively, in the FAS; and 6.33 months vs 6.81 months in PPS.

Tumor burden change at 24-weeks from start of induction therapy in FAS was 0.6% (95% CI, –4.18% to 2.99%).

Overall responses also helped to demonstrate comparative efficacy in the trial arms. At cycle 2, there were 96 (28.5%) partial responses (PRs) in the SB8 group vs 88 (26.8%) in the BEV group; and stable disease was achieved by 202 (59.9%) and 201 (61.3%), respectively.

By cycle 6, the numbers were still close, demonstrating comparability. There were 97 (57.1%) and 83 (49.4%) PRs, respectively; and 60 (35.3%) and 70 (41.7%) SDs, Planchard said. At cycle 6, there was 1 (0.6%) complete response in the BEV group.

In terms of treatment emergent adverse events of special interest, proteinuria was observed in 2 instances in the SB8 arm (0.5%) and 7 patients (1.8%) in the BEV group. Hypertension was noted in 29 (7.7%) and 16 (4.2%) of each group, respectively.

Pharmacokinetic profiles also were highly comparable, Planchard said.

Pegram, director of the Breast Cancer Oncology Program at Stanford Women’s Cancer Center, Stanford University Cancer Institute, California, discussed real world data for biosimilar trastuzumab (SB3, Ontruzant) plus reference pertuzumab in early stage breast cancer.

He noted that a 56% pathological complete response rate (pCR) was noted in 215 Danish patients with HER2-positive breast cancer who received neoadjuvant chemotherapy plus SB3 plus pertuzumab, which he said was exactly comparable to historical trial evidence for the reference drug (Herceptin).

“Indeed, 68% of patients treated in the neoadjuvant setting with node-positive disease converted from lymph node–positive disease to lymph node–negative disease after treatment, so that’s also very reassuring and demonstrates the activity of this trastuzumab biosimilar when combined with pertuzumab,” he said.

In a separate study involving real-world outcomes of 35 patients from Austria with HER2-positive breast cancer who received chemotherapy plus SB3 plus pertuzumab, the safety and efficacy profile of SB3 plus pertuzumab was consistent with that of the reference product in that combination. Significantly, 22 patients treated in the neoadjuvant setting achieved a pCR of 50%; none of the 35 patients had a decline in left ventricular ejection fraction (LVEF) of more than 10%; and 2 patients had an LVEF decline of ≤ 5% after treatment. “This is also very reassuring in terms of cardiac safety signals,” Pegram said.

Importantly, Pegram said, “this recent real-world evidence supports the extrapolation of trastuzumab-dttb [SB3] to include combination [therapy] with pertuzumab.”

1. Planchard D, Pegram MD. Navigating the optimized oncology treatment options in colorectal cancer, lung cancer and breast cancer through multidisciplinary discussions: clinical evidences of biosimilars. Presented at: ESMO Congress Virtual 2020. 5389.

2. Reck M, Luft A, Bondarenko I, et al. A phase III randomized double-blind multicenter study to compare the efficacy, safety, pharmacokinetics, and immunogenicity between SB8 (proposed bevacizumab biosimilar) and reference bevacizumab in patients with metastatic or recurrent nonsquamous non-small cell lung cancer. Lung Cancer. 2020.

ESMO Virtual Congress 2020

Biosimilars from Samsung Bioepis have demonstrated equivalency in clinical trial and real world settings, according to 2 prominent cancer specialists. 

Planchard, Pegram Review Evidence for Samsung Bioepis Biosimilars

At the European Society for Medical Oncology (ESMO) Virtual Congress 2020 this week, detailed presentations will be 

biosimilar studies for agents from Mylan, Samsung Bioepis, and Shanghai Henlius Biotech.

Investigators plan to report phase 3 efficacy and safety data for Mylan’s proposed bevacizumab biosimilar MYL-14020 versus the reference product, Avastin, in the first-line treatment of patients with stage IV nonsquamous non–small cell lung cancer.

Investigators randomized 671 patients to the biosimilar candidate (n = 337) and Avastin (n = 334). In the preconference abstract, they reported that the confidence intervals for objective response rate (ORR) were within the predefined equivalence margins, demonstrating equivalence for MYL-14020.

 that the FDA had accepted its 351(k) filing application for MYL-14020. An application decision date was scheduled for December 27, 2020.

A poster on a randomized equivalence study for the Shanghai Henlius Biotech trastuzumab biosimilar (HLX02) also will be presented at ESMO. The multicenter study randomized women (N = 649) 1:1 to receive intravenous HLX02 or a European Union–marketed version of reference trastuzumab combined with docetaxel, with the primary end point being ORR at week 24.

In their preconference abstract, the investigators reported a 71.3% ORR for HLX02 vs 71.4% for the reference product. The group difference of 

7.0% to 6.9%) was “completely within the predefined equivalence margins of ±13.5%.”

In June, Henlius and Accord received a positive 

 for marketing approval for HLX02 from the European Medicines Agency.

Samsung Bioepis reported phase 3 exploratory 

 for its bevacizumab biosimilar (Aybintio) ahead of the scheduled ESMO poster presentation.

Positive results emerging on oncology biosimilars will be presented at the European Society for Medical Oncology Virtual Congress 2020 this week . 

Positive Equivalency Data for a Trio of Biosimilars Are Reported

positive phase 3 exploratory study results for its bevacizumab biosimilar, Aybintio, which received European Commission 

The findings are set for presentation at the European Society for Medical Oncology (ESMO) Virtual Congress 2020, which begins this week.

The Incheon, Republic of Korea–based company said the study results supported preexisting evidence in support of equivalence between Aybintio and reference bevacizumab in patients with metastatic or recurrent nonsquamous non–small cell lung cancer.

“The data observed in the phase 3 exploratory analyses reinforce equivalent clinical efficacy between Aybintio and reference bevacizumab,” said Seongwon Han, vice president and leader of the Medical & Lifecycle Safety Team at Samsung Bioepis.

The exploratory study enrolled 665 patients, of whom 337 received Aybintio and 328 were treated with reference bevacizumab with paclitaxel and carboplatin every 3 weeks for up to 6 cycles, followed by Aybintio or reference bevacizumab maintenance monotherapy. The risk difference was analyzed in the per-protocol set (PPS) within a predefined equivalence margin of ±12.5%.

The primary end point was overall response rate (ORR) after 24 weeks of induction therapy. In a previous analysis, the ORR in the PPS was 50.1% for Aybintio and 44.8% for reference bevacizumab, and the risk difference by week 24 was 5.3% (95% CI, 

2.2% to 12.9%). The risk difference is a comparative measure of the likely harms and benefits of therapies.

In the current study, the risk differences in best ORR by weeks 11 and 17 was 2.2% (95% CI, 

The mean reduction in tumor burden by week 24 was 

27.3% for reference bevacizumab, with a difference of 0.59% (

Samsung Bioepis said the results of the phase 3 exploratory analyses would be presented in an e-poster at ESMO during the virtual event’s Science Weekend on Thursday, September 17 at 9 AM Central European Summer Time.

Samsung Bioepis' bevacizumab biosimilar demonstrates equivalence in analyses to be presented at the European Society for Medical Oncology Virtual Congress 2020.

Samsung Bioepis Reports Positive Phase 3 Results for Aybintio

Skylar Jeremias is the Managing Editor for The Center for Biosimilars and The American Journal of Managed Care (AJMC).

Biosimilar trastuzumab (Herzuma) in combination with pembrolizumab and chemotherapy was highly effective in reducing tumor size in patients with HER2-positive advanced gastric cancer, according to results of a phase 1b/2 clinical trial.

 trial was designed to evaluate the potential of the combination therapy in light of a growing body of evidence on the positive effects of monoclonal antibodies such as trastuzumab in treating solid tumors.The findings have implications for reducing the costs of care, the authors said.

“With the costs of oncology treatments being so burdensome, the availability of biosimilar trastuzumab could reduce the overall cost by combination treatment with innovative new drugs and chemotherapy,” said Sun Young Rha, MD, PhD, chief of medical oncology at Yonsei University College of Medicine and the lead investigator of the trial, during her presentation on the results at this year's virtual 2020 American Society of Clinical Oncology Annual Meeting.

Investigators in the Republic of Korea enrolled 43 patients and treated them with pembrolizumab (200 mg, day 1), biosimilar trastuzumab (6 mg/kg, day 1), capecitabine (1000 mg/m

 twice daily, days 1-14), and cisplatin (80 mg/m

The treatment duration ranged from 1.4 to 24 months, with a median follow up of 16.1 months. The trial enrolled 43 patients and 11 remained on the regimen.

Investigators found significant tumor shrinkage in 95.3% of patients, and the overall response rate was 76.7%. They said 16.3% of patients experienced a complete response and 60.5%, a partial response. Additionally, the median progression-free survival was 8.6 months (95% CI, 7.2-16.4), and the median overall survival (OS) was 19.3 months (95% CI, 16.5-NA). The investigators also found that positive status for the PD-L1 protein for patients at diagnosis did not significantly affect OS rates.

Treatment-related adverse events (AEs) ≥ grade 3 occurred in 32 (74.4%) patients, including 17 (39.5%) cases of grade 3 or grade 4 neutropenia. Immune-related AEs occurred in 4 (10%) patients. The most common hematologic AEs were decreased neutrophil count and anemia, which occurred in 46.5% and 32.6% of patients, respectively.

Herzuma, developed by Teva Pharmaceuticals USA and Celltrion Healthcare, is indicated for treatment in patients with HER2-positive metastatic breast cancer, early breast cancer, and metastatic gastric cancer.

It was approved for use in the United States in December 2018 and 

 in March 2020, making it the fourth trastuzumab biosimilar to be approved in the United States.

The drug was approved in the European Union in November of 2017 and 

 there in May 2018. Herzuma also is approved in the Republic of Korea, Japan, and Brazil.

Rha SY, Lee CK, Kim HS, et al. Targeting HER2 in combination with anti-PD-1 and chemotherapy confers a significant tumor shrinkage of gastric cancer: A multi-institutional phase Ib/II trial of first-line triplet regimen (pembrolizumab, trastuzumab, chemotherapy) for HER2-positive advanced gastric cancer (AGC). 

. 2020;38(suppl 15; abstract 3081). doi:10.1200/JCO.2020.38.15_suppl.3081

ASCO

A phase 1b/2 trial evaluating a trastuzumab biosimilar as part of a first-line triplet regimen demonstrated significant tumor shrinkage in HER2-positive advanced gastric cancer.

Biosimilar Trastuzumab Effective in Triplet Regimen for Gastric Cancer

What do UK patients think about the process and communication used to switch to adalimumab biosimilars by the National Health Service (NHS) and the local home care trusts?

 at the European Hematology Association (EHA)’s 25th Annual Congress, EHA25 Virtual, not very much.

, even before the results of the tender for adalimumab (reference product Humira) had taken place. The United Kingdom has made no secret of its hopes of significant cost savings on a switch to biosimilar adalimumab, aspiring to save £300 million (approximately US $386 million) of its £400 million (approximately US $514 million) annual spending on adalimumab as a result of using biosimilars.

In the UK setting, self-administered biologics are delivered to patients in their homes by commercial companies that are paid for by pooled funds from the pharmaceutical industry. Once a prescription is initiated by a hospital prescriber, nurses deliver the products and teach patients how to inject their therapy at home.

Nearly 2 years in, researchers sought patient feedback on the switch process with the intent of reporting findings to NHS England. In addition, they sought to give organizations representing rheumatology, dermatology, and gastroenterology patients information to develop any future resources to help improve shared decision making (SDM).

These organizations had worked with National Health Service (NHS) to produce the materials for disseminating information to prescribers and patients, and they now wanted to know how the process was implemented and if SDM was practiced.

A working group of 4 organizations created an online survey asking questions about:

How the individual was communicated with regarding their treatment being switched to a biosimilar

Was there any choice or perceived input into the decision making process

Overall satisfaction on how the individual felt their personal preferences/needs were met

The results demonstrate how challenging the switch process turned out to be.

899 useable responses, with patients identifying as 52% rheumatology, 42% gastroenterology, and 5% dermatology patients; the remaining 1% were “more complex specialties,” the researchers said.

More than half of patients were not asked for their consent before their treatment was switched to a biosimilar adalimumab, while 40% said they gave consent. A minority (7%) couldn’t remember or were unsure if consent was given.

Three-fourths were not at all satisfied or not satisfied with the ability to decline being switched. Just 12% felt that they had been given an option to refuse the switch.

SDM “needs to be put into action not just words,” concluded the authors, who represented the National Rheumatoid Arthritis Society, 1 of the 4 organizations that created the survey. The other organizations were the National Axial Spondyloarthritis Society UK; Crohns’ & Colitis UK; and the Psorarsis Association, UK.

They said they will continue to work with NHS and other stakeholders to make SDM “a reality not just rhetoric.”

EULAR

The UK results show how challenging switching to a biosimilar can be, according to patient groups.  

Looking Back, UK Patients Unhappy With Adalimumab Biosimilar Switch

Upon admission to hospital, patients who had been taking insulin degludec (iDeg) at home may receive inappropriate dosing when switched to another insulin, and this is because physicians tend to have a poor understanding of the pharmacodynamics (PD) and pharmacokinetics (PK) of iDeg, investigators concluded in a study presented at the American Diabetes Association 80th Scientific Sessions online conference.

Lead investigator Jing H Chao, MD, and Irl B. Hirsch, MD, observed widely variable practice in transitioning patients from iDeg to insulin glargine U100 (iG100) upon admission, but for various reasons, patients with type 1 diabetes were found to be at much higher risk of developing hypo- and hyperglycemia than patients with type 2 diabetes.

A key reason for the complexity of transitioning patients from iDeg to iG100 is that iDeg has a half life of 25 hours, more than twice that of iG100, meaning it remains in the body at higher concentrations for longer, up to 42 hours versus 24 for iG100, Chao explained. Hospital-based physicians may not understand this and give patients too much or too little iG100 to maintain insulin levels following home dosing. “Physicians should judiciously determine the amount of insulin to be given,” Chao said.

Part of the reason for the knowledge deficiency may be that iDeg, a Novo Nordisk product, was FDA approved just 5 years ago. An advantage of IDeg is that it enables physicians to achieve a more stable background level of insulin in the body relative to insulin glargine, which “waxes and wanes,” Chao said.

So, when switching to iG100 upon admission, it is important to take into account the different rate at which iDeg is excreted from the body. “By the 24th hour, there is still 50% of the background degludec on board. By contrast, when you have glargine, most of the glargine has already been washed out,” Chao said. “If patients were to receive a 100% glargine dose at the 24-hour mark, that would raise their basal [or background] insulin to 150% of the basal insulin that’s on board at that point.”

In the study, Chao and Hirsch noted that clinicians gave iG100 at 0% to 100% of the home-based iDeg dose anytime between 24 hours and 72 hours after the last iDeg dose, “demonstrating a general lack of understanding of the PK and PD of iDeg and a great need to standardize this transition.”

“Physicians are giving 100% of the glargine at the 24th hour, leading to over-basalization of the insulin,” she said.  Excessive insulin can lead to hypoglycemia and, consequently, altered mental status and potential cardiovascular events, including heart attack.

“Not only do physicians vary the time at which they give the first dose of glargine, they also vary the amount of the glargine they give as compared to the home dose. That part was not surprising to us,” Chao said.

“What is surprising to us is that despite such variable practice, we did not see hypoglycemia in patients with type 2 diabetes, and the reason is that compared with type 1 diabetes, patients with type 2 diabetes have a better buffer in that they continue to secrete a small amount of insulin and continue to secrete some glucagon. These are countering hormones that buffer them and help prevent them from getting hypoglycemia as much as patients with type 1 diabetes,” she said.

Mild hypoglycemia was observed in 2 patients with type 1 diabetes, or 28.6%. there were no cases of hypoglycemia in the type 2 group (n = 32).

Another factor to consider is that patients when admitted tend to be under higher levels of physiologic stress, which causes them to require increased amounts of insulin. So, the tendency on the part of physicians to provide too much iG100 is counterbalanced by the body’s need at this point for more insulin than usual, Chao said. “For these reasons we don’t see hypoglycemia in patients with type 2 diabetes.”

“We found that, to counter the amount of stress-induced hyperglycemia, when patient receives 50% to 75% of the glargine at the 24-hour mark, which leads to total of 100% to 125% background basal insulin level at that time, their blood sugar is actually better controlled,” she said.

“If you give anything up to 49%, that gives them less than their home dose, and is insufficient to cover their basal insulin requirement during a stressful hospitalization.”

Chao and Hirsch are hoping that their study prompts physicians to think more carefully about the PD and PK of iDeg and carefully assess other factors when determining follow-up dosing, such as meals taken, stress from hospitalization, renal function, and whether patients were on a sufficient home dose of insulin to begin with. Renal considerations are key with iDec, because it is not excreted via the kidneys.

The investigators also would like to see further studies conducted, leading to the development of guidelines.

“We’re hoping that prospective trials can be conducted to take a better look at the transition to determine the recommendations on how much insulin glargine to give at what point of their patients’ hospitalization that will ensure patients safety during this complicated transition,” Chao said.

For more about insulin degludec, see these stories about 

Chao JH, Hirsch IB. degludec-to-glargine transition: the first real-world study. Poster presented at: American Diabetes Association 80th Scientific Sessions; June 12-16, 2020. Poster 1025-P.

There is much inconsistency in the way physicians transition patients from insulin degludec to insulin glargine upon hospital admission, leading to higher risk especially for patients with type 1 diabetes, according to a study presented at the American Diabetes Association 80th Scientific Sessions online conference.
 

Doctors Manage Insulin Degludec-to-Glargine Transition Poorly, ADA Study Says

Hi, I’m Skylar Jeremias for The Center for Biosimilars®, your resource for clinical, regulatory, business, and policy news in the rapidly changing world of biosimilars.

The European Hematology Association recently held its 25th Annual Congress, EHA25 Virtual, from June 11 through June 21. The meeting was conducted on a digital platform due to the coronavirus disease 2019 (COVID-19) pandemic and featured some key study findings and presentations on the up-and-coming world of hematology biosimilars.

The following is a summary of our biosimilar coverage from this event:

Investigators produced what they described as the 

 the use of biosimilar erythropoiesis-stimulating agents (ESAs) in patients with myelofibrosis (MF)-related anemia.

Investigators said ESAs are used to manage anemia in hematological malignancies, but scarce evidence exists for the use of these agents in the treatment of MF, and available results are divergent: Response rates range from 23% to 69%, according to the abstract presented at EHA25 Virtual. Until this study, there were no data on the use of biosimilar ESAs in this setting, investigators said.

Investigators reported an 88% overall response rate for a Sandoz rituximab biosimilar in combination with chemotherapy in patients with CD20-positive diffuse large B-cell lymphoma. At the end of treatment, the complete response was 57% and partial response was 31%. Investigators said 61% and 29% of patients experienced enlarged lymph nodes and disease-related pain, respectively.

 presented this month at EHA25 Virtual confirmed findings from the REFLECT study released in 2019, which was the first prospective postapproval study to evaluate a rituximab biosimilar in this context.

 that a rituximab biosimilar developed by Celltrion Healthcare (Truxima) in combination with lenalidomide and acalabrutinib (R2A) in patients with relapsed or refractory aggressive B-cell lymphoma was tolerable and effective.

The addition of rituximab, a targeted therapy, to chemotherapy agents can improve patient outcomes but adds to the financial burden of treatment. Investigators said that exploring the use of biosimilar rituximab may be an avenue to bring down costs.

To read all of these articles, visit our EHA 

Videos

EHA is the annual meetting for the European Hematology Association.

Here is a summary of our coverage from EHA25 Virtual, the annual meeting for the European Hematology Association (EHA).

EHA25 Virtual Roundup

Although adalimumab and etanercept biosimilars have been approved in the United States, these have not yet been brought to market, owing to exclusivity 

. However, European studies investigating real-world applications of these agents are well along, based on presentations at the EULAR 2020 Congress, the virtual meeting of the European League Against Rheumatism.

An Italian study at Padova University Hospital evaluated the rate of switching from originator versions of these drugs to biosimilars in patients with rheumatoid arthritis (RA), psoriatic arthritis (PSA), and axial spondyloarthritis (axSpA). Investigators also evaluated survival for patients who switched to biosimilars versus those who didn’t.

The study enrolled 1208 patients, of whom 560 (46.3%) switched to biosimilars: etanercept (n = 391) or biosimilar adalimumab (n = 169). The mean disease duration was 16 years, and the mean duration of the biologic disease-modifying antirheumatic drug (bDMARD) was 96.3 months.

Investigators said factors associated with switching were longer disease duration, shorter duration of previous bDMARD treatments, and diagnosis. Patients with RA had an almost 3-fold higher likelihood of being switched to biosmilars compared with patients with PSA or axSPA, according to the study. Investigators said the difference between PSA and axSPA in this context was not significant.

A longer drug survival was observed in patients who switched versus those who continued with originator drugs (HR 1.38; 95% CI, 1.2-1.58); however, investigators concluded that switching from the reference biologic to the biosimilar “does not affect the survival of the treatment. Indeed, it provides sustained effectiveness particularly if undertaken in patients with stable disease activity.”

They said longer drug survival was associated with longer disease duration, longer mean duration of previous bDMARDs, and diagnosis.

Investigators also concluded that “patients with longer disease duration and longer bDMARD duration were most likely to be switched successfully to biosimilars.”

In a second switching study, also conducted in Italy, investigators sought to evaluate the safety and retention rate for patients switched from the originator etanercept to the biosimilar (SB4, Benepali).

The study enrolled 220 patients with RA, PSA, and ankylosing spondylitis (AS), juvenile idiopathic arthritis (JIA), and other rheumatic diseases treated with originator etanercept for at least 6 months. Investigators collected data on adverse events, loss of efficacy, and persistence on treatment. The rate of retention, reason for discontinuation, and other management data were collected at 6, 12, and 18 months.

Investigators said the originator biologic was used in various dMARD treatment lines: first, 76.8%; second, 17.7%; third, 3.2 %; and fourth, 2.3%. At a median follow-up of 12.1 months, 50 patients (22.7%) presented with at least 1 nonserious adverse event, with 36 (16.4%) instances of disease re-activation, and 30 (13.6%) interruptions of SB4 treatment, mostly related to safety and efficacy.

They said the retention rates were 99.1% (210/212) at 6 months, 90.9% (150/165) at 12 months, and 81.5% (53/65) at 18 months, respectively.

Of the 30 interruptions in biosimilar treatment, 17 patients were switched back to the originator product; the remaining patients were given a different drug regimen. Investigators said age was the only significant predictor of interruption at 6 months.

Retention rates at 6, 12, and 18 months were not influenced by disease, bDMARD line, conventional synthetic DMARD combination, gender, disease duration or originator etanercept duration.

“Our real-life data confirm the safety profile of switching from ETN to SB4. In our patients, the data show a higher retention rate, when compared to other-real life registries data,” investigators wrote.

Astorri D, Ometto F, Friso L, Raffeiner B, Botsios C, Doria A. Use of TNF-inhibitors biosimilars in chronic inflammatory arthritides: a three-year experience in a large monocentric cohort of patients from the North-East Italy. Presented at: EULAR 2020 Congress; June 3-August 31, 2020. Abstract AB0274.

Bruni C, Gentileschi S, Capassoni M, et al. Safety and retention rate after switching from etanercept originator (ETN) to etanercept biosimilar (SB4) in inflammatory joint diseases: data from real life. Presented at EULAR 2020 Congress; June 3-August 31, 2020. Abstract AB0281.

Studies on switching and retention for adalimumab and etanercept biosimilars yielded positive data, according to abstracts presented at the EULAR 2020 Congress.
 

EULAR Studies Explore Value of Biosimilar Switching

A survey of rheumatologists in France concluded that they generally have a good understanding of biosimilars but lack the confidence to use them, according to data presented at the EULAR 2020 Congress, the virtual meeting of the European League Against Rheumatism.

The study concerned the use of subcutaneously applied tumor necrosis factor inhibitor (SC TNFi) biosimilars, which have been available in France since 2015 at lower cost than reference products. There is no requirement in France that rheumatologists prescribe biosimilars or switch patients to them.

The findings mirror the results of a similar US-based study 

 last year in which rheumatologists expressed hesitancy about switching to biosimilars and extrapolating to uses beyond those the biosimilars were approved for.

French investigators surveyed 101 rheumatologists, 47.1% of whom were younger than 40 years and 92% of whom had authorization to prescribe TNFi.

According to the findings, 53.2% always prescribe biosimilars when prescribing TNFi for the first time, and 78.5% prescribe TNFi biosimilars 90% of the time.

Investigators said 30.6% of French rheumatologists never switch patients from originator drugs to biosimilars. Those who switch patients to biosimilars do it more than 75% of the time.

In the survey, 96.5%, 87.1%, and 91.8% agreed that biosimilars are as efficient, are as safe, and have the same immunogenicity profile as originator products, respectively.

Among rheumatologists who prescribe biosimilars in more than 90% of cases, 77.4% correctly answered no to the question “biosimilars and originators have to be compared in phase III studies for each indication for which the originators received marketing approval.”

Among those who prescribe biosimilars less than 90% of the time, just 31.2% answered this question correctly, indicating to the investigators that those who prescribe biosimilars as initial treatments tend to be equipped with better knowledge of biosimilars. Investigators said this finding was significant (

Rheumatologists were also asked whether there is enough experience with biosimilars. Most rheumatologists who switch to biosimilars more than 75% of the time answered this question in the affirmative, and just 25.4% in this group said there isn’t enough experience with biosimilars.

The same question was asked of those who switch to biosimilars less than 75% of the time. Investigators said a majority of them (57.7%) answered that there isn’t enough experience with biosimilars. This finding also was significant (

De Chateaubriant A, Ingrand P, Gervais E. Anti-TNF biosimilars: how knowledge and belief influence prescription. Presented at: EULAR 2020 Congress; June 3-August 31, 2020. Abstract AB1162.

A study presented at the European League Against Rheumatism conference suggested that French rheumatologists have good knowledge of biosimilars but lack the confidence to use them.

Latest Conference Articles