Biosimilar Pegfilgrastim: Improving Access and Optimising Practice to Supportive Care that Enables Cure.
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SUBMITTER: Cornes P
PROVIDER: S-EPMC7211191 | biostudies-literature | 2020 Jun
REPOSITORIES: biostudies-literature
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Biosimilar Pegfilgrastim: Improving Access and Optimising Practice to Supportive Care that Enables Cure.
Cornes Paul P Gascon Pere P Vulto Arnold G AG Aapro Matti M
BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy 20200601 3
Febrile neutropenia (FN) is a serious complication of chemotherapy, which can cause significant morbidity and mortality, result in dose delays and reductions and, ultimately, reduce cancer survival. Over the past decade, the availability of biosimilar filgrastim (short-acting granulocyte colony-stimulating factor [G-CSF]) has transformed patient access, with clear evidence of clinical benefit at preventing FN at reduced costs. In 2019, seven biosimilar pegfilgrastims (long-acting G-CSFs) were li ...[more]
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Project description:AimsThis study aimed to demonstrate that the pharmacokinetic (PK) and pharmacodynamic (PD) profile of Sandoz proposed biosimilar pegfilgrastim (LA-EP2006) matches reference pegfilgrastim (Neulasta® ) in healthy subjects. Safety and immunogenicity were also assessed.MethodsThe phase I, randomized, double-blind, two-period crossover study consisted of two treatment periods separated by an 8-week washout period. Healthy subjects aged 18-45 were randomized to either proposed biosimilar/reference pegfilgrastim or reference pegfilgrastim/proposed biosimilar. Proposed biosimilar and reference pegfilgrastim were administered on Day 1 of each treatment period (single 6 mg subcutaneous injection). Blood samples for PK/PD analysis were taken predose and ≤336 h postdose. PK/PD similarity was claimed if 90% (PK) and 95% (PD) confidence intervals (CI) for geometric mean ratios of the area under the serum concentration-time curve (AUC) from time of dosing and extrapolated to infinity (AUC0-inf ), or to the last measurable concentration (AUC0-last ), maximum observed serum concentration (Cmax ), absolute neutrophil count (ANC) area under the effect curve from the time of dosing to the last measurable concentration (AUEC0-last ) and ANC maximum effect attributable to the therapy under investigation (Emax ) were completely contained within the predefined margin (0.8 to 1.25).ResultsOverall, 169 subjects completed the study. PK/PD similarity was demonstrated; 90% CIs of geometric mean ratio of proposed biosimilar/reference for PK: AUC0-inf (1.0559-1.2244), AUC0-last (1.0607-1.2328), Cmax (1.0312-1.1909) and 95% CIs for PD (ANC): AUEC0-last (0.9948-1.0366), Emax (0.9737-1.0169) were completely contained within predefined margin of 0.8 to 1.25. Both biologics had similar safety profiles, were well tolerated and had low incidence of anti-drug antibodies. No neutralizing or clinically relevant antibodies were detected.ConclusionsPK/PD similarity of Sandoz proposed biosimilar pegfilgrastim and reference pegfilgrastim was confirmed. No clinically meaningful differences in safety, tolerability and immunogenicity were observed in healthy subjects.
| S-EPMC6256001 | biostudies-literature
Project description:BackgroundThe administrative and professional consequences of access targets for general practices, as detailed in the new GMS contract, are unknown. This study researched the effect of implementing the access targets of the new GP contract on general practice appointment systems, and practice manager satisfaction in a UK primary health care setting.MethodsA four-part postal questionnaire was administered. The questionnaire was modified from previously validated questionnaires and the findings compared with data obtained from the Western Health and Social Services Board (WHSSB) in N Ireland. Practice managers from the 59 general practices in the WHSSB responded to the questionnaire.ResultsThere was a 94.9% response rate. Practice managers were generally satisfied with the introduction of access targets for patients. Some 57.1% of responding practices, most in deprived areas (Odds ratio 3.13 -95% CI 1.01 - 9.80, p = 0.0256) had modified their appointment systems. Less booking flexibility was reported among group practices (p = 0.006), urban practices (p < 0.001) and those with above average patient list sizes (p < 0.001). Receptionists had not received training in patient appointment management in a quarter of practices. Practices with smaller list sizes were more likely than larger ones to utilise nurses in seeing extra patients (p = 0.007) or to undertake triage procedures (p = 0.062).ConclusionThe findings demonstrated the ability of general practices within the WHSSB to adjust to a demanding component of the new GP contract. Issues relating to the flexibility of patient appointment booking systems, receptionists' training and the development of the primary care nursing role were highlighted by the study.
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Project description:BACKGROUND:Despite the benefits biosimilars offer in terms of cost savings and patient access, healthcare professionals and patients have been reluctant to use them. Next to insufficient understanding of and trust in biosimilars, healthcare professionals and patients have questions about switching and the nocebo effect when using biosimilars in clinical practice. In addition, clear motivation to use biosimilars may be lacking among these stakeholders. OBJECTIVE:This study aims to provide recommendations on how to improve biosimilar use on both a clinical and a practical level based on insights from healthcare professionals (physicians, hospital pharmacists, nurses), patients (or their representatives), and regulators across Europe. METHODS:We conducted 44 semi-structured interviews with experts from five stakeholder groups across Europe: physicians, hospital pharmacists, nurses, regulators, and patients/representatives. Interviews were transcribed ad verbatim and transcripts analysed according to the thematic framework method. RESULTS:Based on the insights and considerations of the experts interviewed, we identified a number of recommendations to improve the use of biosimilars in clinical practice. Regarding switch implementation, the experts voiced support for the following actions: (1) disseminate evidence from and experience with (multiple) switching; (2) provide clear, one-voice regulatory guidance about the interchangeability of biosimilars and their reference product; (3) apply a multi-stakeholder implementation and communication protocol to guide switching in clinical practice; (4) apply a pragmatic approach when taking switch decisions; and (5) avoid mandated switching, allowing stakeholder communication and alignment. When discussing approaches to increase the willingness of stakeholders to use biosimilars, we concluded that actions should be centred on (1) communicating the benefits provided by biosimilars and the introduction of market competition, (2) increasing awareness among stakeholders about medicine prices and their societal responsibility to use medicines in a cost-effective manner, (3) transparent reporting about the allocation of savings, (4) sharing biosimilar usage data among hospitals and prescribers to allow peer-to-peer benchmarking, and (5) applying a balanced combination of tangible and non-tangible incentives that can be tailored to offset the time and effort expended by stakeholders when switching to a biosimilar. CONCLUSIONS:This study proposes a number of strategic, practical, and overarching recommendations to support healthcare professionals and inform decision makers to improve the clinical use of biosimilars and the willingness of stakeholders to use them. The proposed solutions to fully realise the potential of biosimilars for healthcare systems and patients include developing practical switch guidance, being transparent about the gains from biosimilar use (and how savings are allocated), and developing a combination of non-tangible and tangible incentives for involved stakeholders.
| S-EPMC7669768 | biostudies-literature
Project description:BackgroundPegfilgrastim is widely used for the prevention of chemotherapy-induced neutropenia. In highly regulated markets, there are currently no approved biosimilars of pegfilgrastim. Pegfilgrastim Randomized Oncology (Supportive Care) Trial to Evaluate Comparative Treatment (PROTECT-2) was a confirmatory efficacy and safety study designed to compare proposed biosimilar LA-EP2006 with reference pegfilgrastim (Neulasta, Amgen) in early-stage breast cancer patients receiving adjuvant or neoadjuvant myelosuppressive chemotherapy.MethodsA total of 308 patients were randomized to LA-EP2006 or reference pegfilgrastim. Each patient received TAC (intravenous docetaxel 75 mg/m(2), doxorubicin 50 mg/m(2), and cyclophosphamide 500 mg/m(2)) on day 1 of each cycle, for six or more cycles. Pegfilgrastim (LA-EP2006 or reference) was given subcutaneously (6 mg in 0.6 mL) on day 2 of each cycle. The primary endpoint was duration of severe neutropenia (DSN) during cycle 1 (number of consecutive days with an absolute neutrophil count <0.5 × 10(9)/L), with equivalence confirmed if 90% and 95% confidence intervals (CIs) were within a 1-day margin.ResultsBaseline characteristics were well balanced. DSN was equivalent between groups at mean ± SD 1.36 ± 1.13 (LA-EP2006, n = 155) and 1.19 ± 0.98 (reference, n = 153) in cycle 1. With a treatment difference (reference minus LA-EP2006) of -0.16 days (90% CI -0.36 to 0.04; 95% CI -0.40 to 0.08), LA-EP2006 was equivalent to reference pegfilgrastim. Secondary efficacy parameters were similar between groups during cycle 1 and across cycles. Safety profiles were also similar between groups. No neutralizing antibodies against pegfilgrastim, filgrastim, or polyethylene glycol were detected.ConclusionLA-EP2006 and reference pegfilgrastim were therapeutically equivalent and comparable regarding efficacy and safety in the prevention of neutropenia in patients with early-stage breast cancer receiving TAC.Implications for practiceThe granulocyte colony-stimulating factor pegfilgrastim is widely used for the prevention of chemotherapy-induced neutropenia. Biosimilars are biologics with similar quality, safety, and efficacy to a reference product that may increase the affordability of treatment compared with their reference compounds. There are currently no approved biosimilars of pegfilgrastim in highly regulated markets. No previous phase III studies have been performed with LA-EP2006. PROTECT-2 was conducted to confirm the similarity of the proposed biosimilar LA-EP2006 to pegfilgrastim. Biosimilar pegfilgrastim (LA-EP2006) may benefit oncology patients by offering increased access to biological treatments that may improve clinical outcomes. This means that patients could potentially be treated prophylactically with biologics rather than only after complications have occurred.
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Project description:To measure the size and timing of changes in utilization and costs for employees and dependents who had major access barriers to primary care removed, across an 8-year period (2007 to 2014).Retrospective observational study examining patterns of utilization and costs before and after the implementation of a worksite medical office in 2010. The worksite office offered convenient primary care services with no travel from work, essentially guaranteed same day access, and no co-pay. Trends in visit rates and costs were compared for an intervention fixed cohort group (employees and dependents) at the employer (n = 1211) with a control fixed cohort group (n = 542 162) for 6 types of visits (primary, urgent, emergency, inpatient, specialty, and other outpatient). Difference-in-differences methods assessed the significance of between-group changes in utilization and costs.The worksite medical office intervention group had an increase in primary care visits relative to the control group (+43% vs +4%, P < 0.001). This was accompanied by a reduction in urgent care visits by the intervention group compared with the control group (-43% vs -5%, P < 0.001). There were no differences in the other types of visits, and the total visit costs for the intervention group increased 5.7% versus 2.7% for the control group (P = 0.008). A sub-group analysis of the intervention group (comparing dependents to employees) found that that the dependents achieved a reduction in costs of 2.7% (P < 0.001) across the study period.The potential for long-term reduction in utilization and costs with better access to primary care is significant, but not easily nor automatically achieved.
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Project description:Kidney supportive care (KSC) integrates kidney and palliative care to improve quality of life for people with chronic kidney disease (CKD). Despite increasing interest and global advocacy to integrate KSC into kidney care, evidence to guide optimal care delivery is limited. This observational cross-sectional study used an online survey to describe current KSC models in Australia, Aotearoa-New Zealand, and the UK. Between April and December 2022, 114 nephrology units responded (response rate 67%), with 66% having a dedicated KSC service (UK, 74%; Australia, 58%; and New Zealand, 67%). Many different health care professionals worked in KSC services with diversity in clinical resources and activities between units and across countries. Overall, funding for KSC services was low, with a median full time equivalent (FTE) per unit (standardized per 100 people receiving hemodialysis [HD]) of 0.51 (interquartile range [IQR], 0.17-1.05) and 4 units provided a service without allocated funding. The scope of KSC service was wide-ranging and prioritized activities included symptom management, psychological support, complex future treatment planning and discussion, and care coordination. There were no significant differences between countries in terms of location of care provision, frequency of review, referral patterns or discharge rates; however, there was variation described within countries. Models of KSC vary markedly across kidney units and between countries. Despite this variation, there was consistency in terms of clinical priorities which were person-centered and focused on physical and psychosocial well-being. Further research is required to evaluate the effectiveness of KSC provision, alongside improved funding methods to ensure sustainable and equitable KSC delivery.
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Project description:Veterans have higher lung cancer incidence and mortality rates than civilians. Frequently, Veterans with lung cancer suffer from undertreated symptoms due to complex comorbidities, limited social support, and reluctance in discussing symptoms with their oncologists. Evidence supports proactive symptom screening among civilians with cancer; however, no studies to date have evaluated whether Veteran volunteer-led proactive symptom screening is feasible and effective among Veterans with lung cancer. The "Improving Supportive Care for Patients with Thoracic Malignancies" study was co-developed by a pre-established Veteran and Family Advisory Board. Veterans with lung cancer are randomized in a 1:1 allocation to either a 9-month intervention combined with usual oncology care (intervention group) or usual oncology care alone (control group). A Veteran volunteer is assigned to all Veterans in the intervention group and conducts weekly symptom assessments using validated symptom surveys and reviews all symptom scores with an oncology nurse practitioner. The primary outcome is to evaluate whether the intervention improves documentation of symptoms at 6 months post-enrollment among Veterans in the intervention group as compared with the control group. Secondary outcomes include changes in patient-reported outcomes (i.e., symptom burden, patient activation, patient satisfaction with decision, health-related quality of life) and differences in acute care use (i.e., emergency department visits, hospitalizations) from baseline (time of enrollment in the study) to 3-, 6-, and 9-months post enrollment. This study addresses a significant concern expressed by Veterans and their caregivers. Findings can advance our understanding of how to improve symptom-burden among Veterans with lung cancer. ClinicalTrials.gov Registration #NCT03216109.
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Project description:Palliative radiotherapy (PRT) is known to be effective in relieving cancer related symptoms. However, many studies and clinical practice show several barriers hindering its use and worsening the quality of patient support during PRT. Various solutions were proposed to overcome these barriers: training on PRT for supportive and palliative care specialists and training on palliative care for radiation oncologists, and introduction of pathways and organizational models specifically dedicated to PRT. Evidence on innovative organizational models and mutual training experiences is few and sparse. Therefore, the aim of this literature review is to present a quick summary of the information available on improving the PRT quality through training, new pathways, and innovative organizational models. The majority of studies on the integration of PRT with other palliative and supportive therapies present low levels of evidence being mostly retrospective analyses. However, it should be emphasized that all reports uniformly showed advantages coming from the integration of PRT with supportive therapies. To actively participate in the integration of PRT and palliative care, providing comprehensive support to the needs of patients with advanced cancer, radiation oncologists should not only plan PRT but also: (i) assess and manage symptoms and stress, (ii) rapidly refer patients to specialists in management of more complex symptoms, and (iii) participate in multidisciplinary palliative care teams. To this end, improved education in palliative care both in residency schools and during professional life through continuous medical education is clearly needed. In particular, effective training is needed for radiotherapy residents to enable them to provide patients with comprehensive palliative care. Therefore, formal teaching of adequate duration, interactive teaching methods, attendance in palliative care services, and education in advanced palliative care should be planned in post-graduated schools of radiotherapy.
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Project description:MSB11455 is a proposed biosimilar to the currently licensed reference pegfilgrastim (Neulasta® ). This study was designed primarily to compare the immunogenicity of MSB11455 and Neulasta® . As secondary objectives, the safety and tolerability of MSB11455 and Neulasta® were also compared. Healthy adult subjects were randomized to either MSB11455 or Neulasta® , stratified by antipolyethylene glycol (PEG) antibody status at screening and study site. Subjects received a single subcutaneous dose of MSB11455 or Neulasta® (both 6 mg/0.6 mL) on day 1 of each of two study periods (same product in both periods), separated by a washout of 28-35 days. Immunogenicity samples were taken predose and up to day 84 post-first dose. Noninferiority was confirmed if the upper limit of the exact one-sided adjusted 95% confidence interval (CI) for the difference in antidrug antibody (ADA)-positive rates was < 10%. Safety was assessed throughout the study. Overall, 336 subjects were randomized and treated (N = 168 in each group). Noninferiority of MSB11455 over Neulasta® was demonstrated for immunogenicity; the difference in confirmed treatment-induced ADA-positive rate between MSB11455 and Neulasta® was -0.6% (upper limit of the exact one-sided adjusted 95% CI: 6.25%). ADAs were mostly directed against the PEG moiety of pegfilgrastim. No filgrastim-specific neutralizing antibodies were detected in either treatment group. Safety and tolerability were as expected for pegfilgrastim, and comparable between treatments. This study supports and strengthens the available evidence for the biosimilarity of MSB11455 to Neulasta® .
| S-EPMC7183238 | biostudies-literature
Project description:Background:Chemotherapy-induced neutropenia is a common result of myelosuppressive chemotherapy treatment. Infections such as febrile neutropenia (FN) are sensitive to the duration of neutropenia as well as the depth of absolute neutrophil count (ANC) at nadir. Filgrastim, a granulocyte colony stimulating factor (G-CSF), can stimulate the function of mature neutrophils. Pegfilgrastim, a long-acting form of filgrastim, has been shown to reduce FN to a greater extent compared to filgrastim. G-CSF agents have been recommended for prophylactic administration with chemotherapy. Apotex developed a proposed pegfilgrastim biosimilar. This study was conducted to confirm that no clinically meaningful efficacy or safety differences exist between Apotex's proposed biosimilar and its reference product. Methods:589 breast cancer patients were randomized and dosed with the proposed pegfilgrastim biosimilar, US-licensed pegfilgrastim reference product, or EU-approved pegfilgrastim reference product. The primary endpoint assessed was the duration of severe neutropenia (DSN) and secondary endpoints included rate of FN and ANC nadir. Results:Data showed that the mean DSN, the primary endpoint measured, was comparable across all three treatments. The As Treated arm had a 95% confidence interval within the equivalence range for the proposed pegfilgrastim biosimilar with the US-licensed and EU-approved pegfilgrastim reference products. Secondary endpoints, which included depth and peak of ANC nadir, time to ANC recovery post-nadir and rates of FN, also showed similarity between the three different treatment groups. The adverse event incidence was similar across treatment arms and there were no unexpected safety events. Conclusions:Overall, these results show that the proposed pegfilgrastim biosimilar is similar to Amgen's US-licensed and EU-approved pegfilgrastim reference products with regard to the clinical efficacy and safety endpoints assessed.Trial registration EMA: European Union Clinical Trials Register: (https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-002678-21) Eudract # 2011-002678-21 Registered: 01/10/2012.
| S-EPMC6127997 | biostudies-literature