Approval Of Biosimilars Research Articles

A descriptive study of new drug approvals during 2017-2021 and disease morbidity and mortality patterns in India.

Studies show the presence of a mismatch between drug research and disease burden. A study conducted in the European Union found that new drug development was restricted to certain diseases. A study of biosimilar approvals in India found that 87% of drugs were for treating noncommunicable diseases. This study aimed to determine the new drugs approved in India from 2017 to 2021 and the top ten causes of morbidity and mortality and detect the presence of any discordance between these. A descriptive study was conducted using data on new drug approvals accessed from the Central Drugs Standard Control Organization website. The top ten causes of mortality and morbidity in India from 2015 to 2019 were identified from the Global Burden of Diseases database. Descriptive statistics were used to compare the drug approvals and the leading diseases. One hundred twenty-six drugs were approved during the study period. Antineoplastic drugs constituted 19.84% of the approvals, antimicrobials 18.25%, and cardiovascular drugs 9.52%. Ischemic heart disease and chronic obstructive pulmonary disease were the two leading causes of morbidity and mortality. Diarrheal diseases, lower respiratory tract infection, and drug-susceptible tuberculosis were among the top ten causes. Ten antibacterials, including four antitubercular drugs, were approved during this period. Two drugs were approved for rare diseases. Our study showed that the drugs approved were largely in line with the prevalent disease burden, and there was no significant discordance observed. Some diseases, such as ischemic stroke/intracranial hemorrhage, require further efforts in bringing forth newer pharmacotherapy options.

Pharmacokinetic and pharmacodynamic bioequivalence of Gan & Lee insulin analogues aspart (rapilin®), lispro (prandilin®) and glargine (basalin®) with EU- und US-sourced reference insulins.

For the successful approval and clinical prescription of insulin biosimilars, it is essential to show pharmacokinetic (PK) and pharmacodynamic (PD) bioequivalence to the respective reference products sourced from the European Union and the United States. Three phase 1, randomized, double-blind, three-period crossover trials compared single doses of the proposed biosimilar insulin analogues aspart (GL-Asp, n = 36), lispro (GL-Lis, n = 38) and glargine (GL-Gla, n = 113), all manufactured by Gan & Lee pharmaceuticals, to the respective EU- and US-reference products in healthy male participants (GL-Asp and GL-Lis) or people with type 1 diabetes (GL-Gla). Study participants received 0.2 U/kg (aspart and lispro) or 0.5 U/kg (glargine) of each treatment under automated euglycaemic clamp conditions. The clamp duration was 12 h (aspart and lispro) or 30 h (glargine). Primary PK endpoints were the total area under the PK curves (AUCins.total ) and maximum insulin concentrations (Cins.max ). Primary PD endpoints were the total area under the glucose infusion rate curve (AUCGIR.total ) and maximum glucose infusion rate (GIRmax ). Bioequivalence to both EU- and US-reference products were shown for all three GL insulins. Least squares mean ratios for the primary PK/PD endpoints were close to 100%, and both 90% and 95% confidence intervals were within 80%-125% in all three studies. There were no noticeable differences in the safety profiles between test and reference insulins, and no serious adverse events were reported for the GL insulins. GL-Asp, GL-Lis and GL-Gla are bioequivalent to their EU- and US-reference products.

Biosimilars approvals by thirteen regulatory authorities: A cross-national comparison

Biosimilars are biological medicines highly similar to a previously licensed reference product and their licensing is expected to improve access to biological therapies. This study aims to present an overview of biosimilars approval by thirteen regulatory authorities (RA). The study is a cross-national comparison of regulatory decisions involving biosimilars in Argentina, Australia, Brazil, Chile, Canada, Colombia, Europe, Hungary, Guatemala, Italy, Mexico, Peru and United States. We examined publicly available documents containing information regarding the approval of biosimilars and investigated the publication of public assessment reports for registration applications, guidelines for biosimilars licensing, and products approved. Data extraction was conducted by a network of researchers and regulatory experts. All the RA had issued guidance documents establishing the requirements for the licensing of biosimilars. However, only three RA had published public assessment reports for registration applications. In total, the investigated jurisdictions had from 19 to 78 biosimilars approved, most of them licensed from 2018 to 2020. In spite of the advance in the number of products in recent years, some challenges still persist. Limited access to information regarding the assessment of biosimilars by RA can affect confidence, which may ultimately impact adoption of these products in practice.

Comparative stability study and aggregate analysis of Bevacizumab marketed formulations using advanced analytical techniques

Bevacizumab (Bvz) is the most preferred recombinant humanized monoclonal antibody in biosimilar development due to its prominence as a standard treatment in the oncology space. Therapeutic monoclonal antibodies are typically more complex and unlikely to produce a replica. As a result, regulatory agencies allow approval of biosimilars that differ structurally and functionally from their reference product, but these differences should not have any clinical significance. To identify these significant discrepancies, it is essential to perform a thorough characterization of critical product attributes both in real-time and after storage until the product's expiration. In the present study, two Bvz biosimilar brands (Bio-1 and Bio-2) marketed in India were evaluated and compared with the reference product Avastin® to assess their degree of similarity. A comprehensive physicochemical characterization of biosimilars and reference product was performed using orthogonal techniques including LC-ESI-QTOF, MALDI-TOF, FTIR-ATR, iCIEF, rCE, nrCE, UV280, and RP-HPLC. Furthermore, Bvz formulations under study were subjected to various stress conditions of thermal (elevated temperature 50 ± 2 °C), chemical (acidic pH 3.0 ± 0.2, neutral pH 7.0 ± 0.2, and basic pH 10.0 ± 0.2), and mechanical (agitation 200 rpm) for comparative stability evaluation. Any alteration in the secondary structure of the native protein was detected and quantified using far-UV circular dichroism (CD), indicating an average of 15% and 11% loss in native antiparallel β-sheet conformation respectively in Bio-1 and Bio-2 upon exposure to elevated temperature and high pH. Additionally, covalent or non-covalent aggregates formed as a function of elevated temperature and agitation were quantified using SEC-MALS.

Impact of switching between reference biologics and biosimilars of tumour necrosis factor inhibitors for rheumatoid arthritis: a systematic review and network meta-analysis

What is the impact of switching between biologics and biosimilars of adalimumab, etanercept, and infliximab on efficacy and safety for rheumatoid arthritis? A systematic review and network meta-analysis were performed to compare switching and non-switching groups of treatments. Pooled Risk Relative (RR) or standardised mean differences (SMD) with 95% credible intervals (95% CrIs) were obtained. Seventeen randomized trials with a switching phase involving 6,562 patients were included. Results showed that a single switch from biologics to biosimilars compared to continuing biologics had comparable effects for primary and co-primary outcomes, the American College of Rheumatology criteria with 20% response (ACR20) (7 trials, 1,926 patients, RR 0.98, 95% CrIs 0.93 to 1.03) and the Health Assessment Questionnaire—Disability Index (HAQ-DI) (5 trials, 1,609 patients, SMD − 0.07, 95% CrIs − 0.23 to 0.1), and within the equivalence margins: ACR20 [RR 0.94, 1.06] and HAQ-DI [SMD − 0.22, 0.22]. The risk of treatment-emergent adverse events, discontinuation, and positive anti-drug antibodies were comparable after switching. Safety results were imprecise, and the follow-up period might not be sufficient to evaluate long-term effects, especially malignancies. Overall, the practice of single switching between approved biologics and biosimilars of Tumour Necrosis Factor inhibitors is efficacious and safe for rheumatoid arthritis.

Future Evolution of Biosimilar Development by Application of Current Science and Available Evidence: The Developer's Perspective.

Biosimilars have been available in the USA for over a decade, and in Europe for almost two decades. In that time, biosimilars have become established in the treatment landscape for a wide range of diseases, facilitating patient access and affordability of healthcare. However, patients can still struggle to access biological therapies in some markets. There is a need to streamline the process of developing biosimilars without compromising their quality, safety, or efficacy. This opinion piece considers the efficiencies that could be achieved within the biosimilar approval process. In clinical trials for biosimilars, clinical efficacy endpoints have been shown to be lesssensitive measures of biosimilarity than biochemical, biophysical, and biological functional assays. Additional clinical efficacy studies comparing potential biosimilars and reference products do not add information that is useful for regulatory purposes. Large clinical studies of biosimilars with immunogenicity endpoints are of limited value, given the quality control processes in place for all biologics, including biosimilars. The expectation for multiple-switch studies for US interchangeability designation should be reconsidered immediately, and the category should be eliminated in the future. As biosimilars are typically approved globally based on a single set of clinical trials, and all subsequent manufacturing changes are already carefully monitored by regulatory authorities, comparative pharmacokinetic testing of EU and US reference products is unnecessary. Manufacturers and regulators could take greater advantage of existing real-world evidence. Streamlining biosimilar development would enable biosimilar development of more and a wider variety of biological drugs, accelerating biosimilar development without impacting patient safety or effectiveness.

Biosimilars for the next decade in Latin America: a window of opportunity

ABSTRACT Introduction Biosimilars are gaining popularity in Latin America (LA). The biosimilars market is expected to grow rapidly over the next decade as a cost-effective alternative to expensive patented biologics. The drivers for the growing demand include needs for affordable health care, the prevalence of chronic diseases, expiration of patents for numerous biologic medicines and the advent of artificial intelligence (AI). Countries such as Argentina, Brazil and Mexico have implemented regulatory frameworks for the approval of biosimilars as well as for investment in local manufacturing capacity, sale, and distribution. Some LA countries face challenges related to low quality institutional frameworks and deficient public policies for regulatory harmonization of these medicines. Areas covered The aim of this article is to analyze the broad window of opportunity for biosimilars in LA (Brazil, Mexico and Argentina) in the next decade, considering their regulations and institutional quality, as well as an affordable cost for patients with chronic diseases and highlight the biosimilars approved in the three countries studied. Likewise, the future contribution of AI in the drug R&D process is considered. Expert opinion Preparing the next decade of biosimilars in LA will involve improving international regulatory frameworks, institutional quality, investments and capacity in R&D (competencies, infrastructure, and AI).

The status and preparation for the next decade of biosimilars in the Middle Eastern and North African region

ABSTRACT Introduction Little is known about the status and the future potential of biosimilars in the Middle East and North Africa (MENA) region. Areas covered This perspective provides insights into the current regulatory landscape of some MENA countries, currently available biosimilars, the potential of biosimilars in the next decade, and challenges to overcome. Expert opinion Given the economic and demographic heterogeneity across the MENA countries, biosimilars could reduce significant economic unmet needs in these countries. In the next decade, biosimilars may witness higher approval rates and market share over their originators in the MENA countries. We argue that the regulatory bodies in the MENA countries should adopt the new policies of the FDA, the EMA, and the WHO, that aim to ease the biosimilar approval process. These policies are to adopt technology in the process of approval; engage health technology assessment bodies in price assessment; provide educational materials to increase awareness among providers, patients, and payers. Further, MENA countries should upgrade the external-reference pricing systems to more sophisticated ones that consider the heterogeneity in economics and needs.

Potential for biosimilars in rheumatology in Africa

Biosimilars are products which are highly similar to a reference biologic product (RBP). In Africa, regulatory frameworks for biosimilar approval are still in development in many countries and few biosimilars...

Biosimilars in dermatology: identifying myths and knowledge gaps.

Biosimilars are beginning to gain regulatory approval in the United States. Biosimilars are structurally near identical to the innovator and must demonstrate identical pharmacokinetics via the same binding affinity and biological function on assays. However, biologics are so complex that even the innovator company cannot produce exact duplicates; there is batch-to-batch variation. The International Psoriasis Council has outlined a biosimilarity index, which aims to standardize preclinical definitions of biosimilarity. Such an index, paired with post-approval monitoring, could provide a transparent, quantitative definition of biosimilarity. Such an index could increase trust in biosimilar medicines and the preclinical assessment process without increasing costs. As preclinical analyses are critical to biosimilar approval, manufacturers should devote proportionate resources to completing them. Dermatologists, who might reflexively look for indication-specific clinical data, might also shift their focus to preclinical variables. Finally, it should be noted that biosimilars provide more evidence of similarity than we have for different batches of the innovator product. Thus, any clinical testing standards, or lack thereof, for different batches of innovator products should also apply to biosimilars.

Cost-efficiency analysis and expanded treatment access modeling of conversion to rituximab biosimilars from reference rituximab in Jordan

AimTo assess the cost-efficiency and expanded access of three rituximab biosimilars versus the reference rituximab from the perspective of the Jordanian national health payer.MethodsA 1-year cost-efficiency and expanded access model of conversion from reference rituximab (Mabthera) to the approved biosimilars (Truxima, Rixathon, and Tromax) to assess five metrics: total annual cost to treat a hypothetical patient; head-to-head cost comparison; changes in patients’ access to rituximab; number-needed-to-convert (NNC) to provide an additional 10 patients access to a rituximab treatment; and relative amount of Jordanian Dinar (JOD) spent on rituximab options. The model included rituximab doses at 100 mg/10 ml and 500 mg/50 ml and considered both cost-saving and cost-wastage scenarios. Costs of treatments were based on the fiscal year 2022 tender prices received by the Joint Procurement Department (JPD).ResultsRixathon was associated with the lowest average annual cost per patient (JOD2,860) across all six indications among all rituximab comparators, followed by Truxima (JOD4,240), Tromax (JOD4,365) and reference Mabthera (JOD11,431). The highest percentage of patient access to rituximab treatment (321%) was achieved when switching patients from Mabthera to Rixathon in the RA and PV indications. At four patients, Rixathon was associated with the lowest NNC to provide an additional 10 patients access to rituximab treatment. For each JOD1 spent on Rixathon, an additional JOD3.21 must be spent on Mabthera, an additional JOD0.55 on Tromax, and an additional JOD0.53 on Truxima.ConclusionRituximab biosimilars were associated with cost savings in all approved indications in Jordan compared to reference rituximab. Rixathon was associated with the lowest annual cost, the highest percentage of expanded patient access for all six indications, and the lowest NNC providing 10 additional patients with access.

Biosimilar uptake and cost savings analysis before and after implementation of a pharmacist-driven substitution program within a National Community Oncology Network: One-year follow-up.

6516 Background: As of December 2022, 22 of the 40 biosimilar approvals in the United States, are used for the treatment of cancer or for the supportive care of patients with cancer. Our organization is a network of community oncology practices, representing 107 oncologists at 76 locations across 17 states. Because our network faces formulary selection and reimbursement challenges related to a diverse payor mix across multiple states, we sought to see the impact of utilizing regional clinical pharmacists (RCPs) to assist with selection of the most cost-effective biosimilar products. Methods: In October 2021, our network initiated an RCP-driven biosimilar substitution program, whereby the RCP acts as a liaison between providers and financial teams to evaluate existing drug orders and their financial impact. We previously presented data on the financial impact to payors and providers before and after implementation of the program from 4/1/2021 to 4/1/2022. This study evaluates the one-year results following program implementation. Additionally, outcomes related to biosimilar utilization as well as financial impacts to payors, patients, and providers were assessed. Payor savings is defined as the difference of the calculated 80% Medicare ASP+6 for the administered biosimilar compared to the originator; patient savings is defined as the difference of the calculated 20% Medicare ASP+6 co-insurance for the administered biosimilar compared to the originator; provider savings is defined as the difference between the invoiced cost of the biosimilar compared to the originator. Results: By the end of 2022, preferred product utilization was achieved for >90% of bevacizumab, trastuzumab, and rituximab orders. Use of the preferred pegfilgrastim product increased from <20% in 4/2021 to >60% by 12/2022. Use of filgrastim biosimilar product increased from <75% in 4/2021 to >90% by 4/2022, then decreased to 55% by 12/2022 due to trending ASP. Payor preference prevented biosimilar switching in approximately 34% of cases. Conclusions: Use of institution-preferred biosimilar products increased across all agents in this study after implementation of the RCP-driven biosimilar substitution program, except for filgrastim. Significant cost savings were noted for payors, patients, and providers. Barriers to switching to institution-preferred products included non-medical switching requirements by payors, patient assistance and compassionate use programs, and patient and/or provider preferences. [Table: see text]

DEMOCRATIC DELIBERATION TO ASSESS VETERAN PREFERENCES FOR BIOSIMILAR MEDICATION SWITCHING FOR THE TREATMENT OF INFLAMMATORY BOWEL DISEASE IN A RESOURCE CONSCIOUS SETTING

To optimize care while being resource conscious, the Veterans Health Administration (VHA) must develop equitable policies that incorporate Veterans’ values and beliefs. Switching patients with Inflammatory Bowel Disease (IBD) from biologic medications (originators) to less expensive biosimilars offers the opportunity to explore potential policies. Unlike originators, the FDA did not require disease-specific randomized controlled trials for approval of biosimilars, creating provider and patient concerns about the safety of switching to these medications. Deliberative democratic (DD) methods allow us to assess Veteran views of switching programs, a necessary step in creating equitable policy approaches.

P600 Democratic deliberation to assess Veteran preferences for biosimilar medication switching for the treatment of Inflammatory Bowel Disease in a resource-conscious setting.

Abstract Background Optimizing care while being resource-conscious, the Veterans Health Administration (VHA) must develop equitable policies incorporating Veterans’ values and beliefs. Switching patients with Inflammatory Bowel Disease (IBD) from biologic medications (originators) to less expensive biosimilars offers opportunities to explore potential policies. Unlike originators, the FDA did not require disease-specific randomized controlled trials for approval of biosimilars, raising provider and patient concerns about the safety of switching to these medications. Deliberative democratic (DD) methods allow us to assess Veteran views of switching programs, a necessary step in creating equitable policies. Methods We carried out two 2-day sessions with Veterans from the Ann Arbor VA (n=17) and Houston VA (n=12). Deliberation began with education about IBD, the use of biologics (including biosimilars), and related implementation challenges. Participants engaged in facilitated small group discussions to 1) identify Veterans views about biosimilar switching and Veteran preferences about switching, and 2) evaluate five approaches for switching: (a) “status quo”–switching policies vary by VHA facility, (b) “sickest last”–Veterans with severe IBD are switched last, (c) “opt-out”–Veterans may opt-out of switching, (d) “next appointment”–Veterans are switched at follow-up, and (e) “lottery”–patients are switched based on random selection. Participants ranked options (1=most preferred, 5=least preferred) and proposed modifications to these approaches. Participants completed pre- and post-DD session surveys. Transcripts were analysed using qualitative methods. Results Participant demographics are in Table 1. Most Veterans sessions preferred the “sickest last” (mean rank: 1.8, standard deviation: 0.9) or “opt-out” (2.4,1.4) approaches over the “status quo” (3.1,1.0) or “lottery” (4.6,0.9); preferences did not significantly change after deliberation (Figure 1). Preferences reflected Veterans’ concerns about the risk of switching to biosimilars for the most vulnerable Veterans and their strong preference for transparency around biosimilar switching. Participants emphasized the importance of informed choice, prioritizing based on health status, personalization, and shared decision-making. Conclusion DD methods are effective for soliciting Veterans' opinions and preferences for health policies. Veterans favoured policies that provided information and control, promoted shared decision-making, and reduced risk to vulnerable patients. Incorporating patient preferences and insights is critical when implementing health policies in the VHA and other resource-limited settings.

DEMOCRATIC DELIBERATION TO ASSESS VETERAN PREFERENCES FOR BIOSIMILAR MEDICATION SWITCHING FOR THE TREATMENT OF INFLAMMATORY BOWEL DISEASE IN A RESOURCE CONSCIOUS SETTING

Abstract BACKGROUND To optimize care while being resource conscious, the Veterans Health Administration (VHA) must develop equitable policies that incorporate Veterans’ values and beliefs. Switching patients with Inflammatory Bowel Disease (IBD) from biologic medications (originators) to less expensive biosimilars offers the opportunity to explore potential policies. Unlike originators, the FDA did not require disease-specific randomized controlled trials for approval of biosimilars, creating provider and patient concerns about the safety of switching to these medications. Deliberative democratic (DD) methods allow us to assess Veteran views of switching programs, a necessary step in creating equitable policy approaches. METHODS We carried out two 2-day sessions with Veterans from the Ann Arbor VA (n=17) and Houston VA (n=12). Deliberation began with education about IBD, use of biologics (including biosimilars), and related implementation challenges. Participants engaged in facilitated small group discussions designed to 1) identify Veterans views about biosimilar switching and their preferences for informing Veterans about switching, and 2) evaluate responses to five approaches for switching: (a) “status quo”–switching policies vary by VHA facility, (b) “sickest last”–Veterans with the most severe IBD are switched last, (c) “opt-out”–Veterans may opt-out of switching, (d) “next appointment”–Veterans are switched at their next appointment, and (e) “lottery”–patients are switched based on random selection. Participants ranked options (1=most preferred, 5=least preferred) and proposed modifications to these approaches. Participants completed pre- and post-DD session surveys. Discussion transcripts were analyzed using qualitative methods. RESULTS Participant demographics are in Table 1. Most Veterans sessions preferred the “sickest last” (mean rank: 1.8, standard deviation: 0.9) or “opt-out” (2.4,1.4) approaches over the “status quo” (3.1,1.0) or “lottery” (4.6,0.9); preferences did not significantly change after deliberation (Figure 1). Preferences reflected Veterans’ concerns about the risk of switching to biosimilars for the most vulnerable Veterans and their strong preference for information and transparency around biosimilar switching. Participants emphasized the importance of informed choice, prioritizing based on health status, personalization, and shared decision-making (e.g., treatment should be geared to individual patient in discussion with their provider). CONCLUSION DD methods are effective for soliciting Veterans' opinions and preferences for health policies. Veterans favored policies that provided information and control, promoted shared decision-making, and reduced risk to vulnerable patients. Incorporating patient preferences and insights is critical when implementing health policies in the VHA and other resource-limited settings.

Pharmacodynamic Biomarkers for Biosimilar Development and Approval: A Workshop Summary.

The US Food and Drug Administration (FDA) Biosimilars Guidance describes how biosimilars may be approved based on clinical pharmacokinetic and pharmacodynamic (PD) biomarker data, without comparative clinical studies with efficacy end points. This type of clinical development program, however, has only been implemented for a small number of FDA-approved biosimilar products over the last decade. To encourage the use of PD biomarkers in biosimilar development and approval, the Duke-Margolis Center for Health Policy collaborated with the FDA to host a two-day virtual public workshop entitled "Pharmacodynamic Biomarkers for Biosimilar Development and Approval" on September 20-21, 2021. The public workshop was a forum for global regulators, biopharmaceutical developers, and academic researchers to discuss the current and future role of PD biomarkers in improving the efficiency of biosimilar development and approval. The workshop objectives included: (i) discuss the current and potential future state of leveraging PD biomarkers for biosimilar development and approval; (ii)summarize the FDA's initiatives to advance biosimilar development; (iii) describe stakeholders' experience with PD biomarkers in biosimilar development; and (iv) explain research efforts to promote broader application of PD biomarkers in biosimilar development. This document summarizes presentations and panel discussions from each session of the two-day September 2021 public workshop covering the application of PD biomarkers for biosimilar development.

Frequency of Approval and Marketing of Biosimilars With a Skinny Label and Associated Medicare Savings

This cohort study assesses the frequency of approval and marketing of skinny-label biosimilars and their savings to Medicare.

Proposal of International Council for Harmonization (ICH) Guideline for the Approval of Biosimilars

ABSTRACT Objectives Since the initial release of biosimilars 18 years ago, regulations for their licensing have changed considerably; however, there is no global consensus on these regulations. Establishing harmonized regulatory guidelines for the approval of biosimilars with support from the ICH, an independent, non-profit association under Swiss law, will significantly enhance the affordability of biological drugs. Methods Regulatory guidelines from the Food and Drug Administration (FDA), European Medicines Agency (EMA), Medicines and Healthcare products Regulatory Agency (MHRA), and World Health Organization (WHO) were analyzed for historical changes and elements critical to the safety and efficacy of biosimilars. Results Analysis of all EMA and FDA filings show that none of the animal testing and clinical efficacy testing failed because animals do not have the required receptors to initiate pharmacologic responses, and efficacy studies cannot be statistically powered to conclude any results. New analytical technologies will enable good biosimilarity determination, avoiding both tests. Conclusion Scientifically based ICH guidelines that remove redundant studies will reduce development costs, improve safety, and allow global drug distribution based on single compliance. These guidelines are particularly necessary for emerging countries lacking the expertise and resources to evaluate biosimilar filings.

Disease Characteristics and Treatment Outcomes with HLX01: A Real-World Study in Patients with B-Cell Non-Hodgkin Lymphoma in China

Introduction B-cell non-Hodgkin lymphoma (NHL) is the most common hematological malignancy encompassing heterogenous subtypes (Dotan et al., PT 2010). Rituximab (R) has changed the treatment landscape of NHL; approvals of rituximab biosimilars have improved access to and the affordability of this treatment (Mohammed et al., J Blood Med 2019). HLX01 is the first rituximab biosimilar approved for the treatment of NHL and chronic lymphocytic leukemia in China. In a Phase 3 trial enrolling patients with diffuse large B-cell lymphoma (DLBCL), HLX01 demonstrated bioequivalence to reference rituximab in terms of efficacy and safety (Shi et al., J Hematol Oncol 2020). The current study is an ongoing, observational study with the objectives of characterizing the distribution of B-cell NHL subtypes in patients receiving HLX01 and assessing the effectiveness and safety of HLX01 in patients with B-cell NHL subtypes in a real-world setting in China. Methods This multicenter, real-world study enrolled adult patients with pathologically confirmed B-cell NHL subtypes at 40 hospitals in China. HLX01 (either as monotherapy or combination therapy) was recommended, but the selection of treatment regimen was at the investigator's discretion. The primary endpoint was the distribution of B-cell NHL subtypes in patients receiving HLX01. Secondary endpoints were objective response rate (ORR) and complete response (CR) rate in patients with B-cell NHL and progression-free survival (PFS) and overall survival (OS) rates at 1, 3, and 5 years in subgroups categorized by disease characteristics. Response was evaluated every 6 weeks until disease progression or end of treatment, using the Lugano 2014 criteria. After treatment, disease and survival status were followed up every 2 months. Safety was monitored until 1 month after treatment completion. Here, we report results from baseline to 1-year follow-up. Results Between April 2020 and June 2021, 2053 patients were enrolled; of these patients, 1898 had evaluable efficacy data (full analysis set [FAS]) and 1878 had completed ≥ 5 treatment cycles (per-protocol set [PPS]). Overall, the most common subtype was DLBCL (1231/2053, 60.0%), followed by follicular lymphoma (293/2053, 14.3% [Table 1]). Among patients in the FAS, R-CHOP was the most commonly used regimen (1006/1898, 53.0%). Other regimens included BR (175/1898, 9.2%), R monotherapy (150/1898, 7.9%), R2 (63/1898, 3.3%), R-EPOCH (56/1898, 2.95%), DA-R-EPOCH (48/1898, 2.5%), R-DA-EDOCH (18/1898, 0.95%), R-EDOCH (11/1898, 0.58%), and others (371/1898, 19.5%). In the FAS, 868 (45.7%) patients had CR/CRu (CR + unconfirmed CR) and 883 (46.5%) had partial response, contributing to an ORR of 92.3%; in the PPS, the ORR was 93.2%. In 215 patients with evaluable OS and PFS data, median OS and PFS were not reached, and 1-year OS and PFS rates were 90.7% and 74.4%, respectively. In patients with DLBCL in the FAS, 519 (45.5%) had CR/CRu and the ORR was 91.8%. In 139 evaluable patients with DLBCL, 1-year OS and PFS rates were 91.3% and 75.6%, respectively. The ORRs in most subtypes exceeded 90% (Table 2). Among all patients, 423 (20.6%) experienced adverse events (AEs), most of which were grade 1 or 2 in severity. The most common AEs were decreased white blood cell count (3.9%), decreased neutrophil count (3.5%), and nausea/vomiting (3.3%). Conclusions DLBCL is the most common subtype in HLX01-treated patients with B-cell NHL in China. HLX01 showed clinical benefits with favorable safety profiles in patients with B-cell NHL subtypes in a real-world setting. Clinical trial identification: ChiCTR2000032263. Research funding: None. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Prescriber Perspectives on Biosimilar Adoption and Potential Role of Clinical Pharmacology: A Workshop Summary.

The approval and adoption of biosimilar products are essential to contain increasing healthcare costs and provide more affordable choices for patients. Despite steady progress in the number of the US Food and Drug Administration (FDA) biosimilar approvals over the years, biosimilar adoption in the United States has been slow and gradual, largely driven by payers rather than clinicians. In order to better understand the barriers to biosimilar adoption in the clinic, the University of Maryland Center of Excellence in Regulatory Science and Innovation (M-CERSI) and the FDA jointly hosted a virtual workshop on April 13, 2022, titled "Biosimilars: A Decade of Experience and Future Directions - Strategies for Improving Biosimilar Adoption and the Potential Role of Clinical Pharmacology." This summary documents the experiences of four leading academic clinicians with specialties in oncology, rheumatology, gastroenterology, and endocrinology and their perspectives on how to increase biosimilar adoption, including the role of clinical pharmacology. Besides systemic changes in pricing and reimbursement, there is a need for additional education of a broad range of providers, including advanced care practitioners, and patients themselves. Educational efforts highlighting the rigor of the studies that support the approval of biosimilars-including the clinical pharmacology studies-and the benefits of biosimilars, can play a major role in improving biosimilar acceptance.