A phase I pharmacokinetics study comparing PF-06439535 (a potential biosimilar) with bevacizumab in healthy male volunteers

Knight, Beverly; Rassam, D.; Liao, Shiyong; Ewesuedo, Reginald

doi:10.1007/s00280-016-3001-2

Cited by 47 publications

(60 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarity between PF-06439535 and bevacizumab-EU was also demonstrated in a nonclinical toxicity study in cynomolgus monkeys [6]. In the clinical program, the PK similarity of PF-06439535 to both bevacizumab-EU and bevacizumab-US, and of bevacizumab-EU to bevacizumab-US, was demonstrated in a randomized, three-arm study in healthy males (Study B7391001; NCT02031991) [7]. The PK of the three products was compared after a single intravenous (IV) dose of 5 mg/kg.…”

Section: Introductionmentioning

confidence: 74%

Population pharmacokinetic modeling of PF-06439535 (a bevacizumab biosimilar) and reference bevacizumab (Avastin®) in patients with advanced non-squamous non-small cell lung cancer

Sweeney

Cronenberger

2019

Cancer Chemother Pharmacol

View full text Add to dashboard Cite

The objectives of this analysis were to characterize the population pharmacokinetics (PK) of PF-06439535 (a bevacizumab biosimilar) and reference bevacizumab (Avastin ®) sourced from the European Union (bevacizumab-EU) in patients with advanced non-squamous non-small cell lung cancer (NSCLC), and to quantify the difference in PK parameters between the two drug products via covariate analysis. Methods Pooled PF-06439535 and bevacizumab-EU serum concentration data from a comparative clinical efficacy and safety study (NCT02364999) in patients with NSCLC (N = 719) were analyzed using a non-linear mixed-effects modeling approach. Patients received PF-06439535 plus chemotherapy or bevacizumab-EU plus chemotherapy every 21 days for 4-6 cycles, followed by monotherapy with PF-06439535 or bevacizumab-EU. PF-06439535 or bevacizumab-EU was administered intravenously at a dose of 15 mg/kg. Effects of patient and disease covariates, as well as the drug product (PF-06439535 versus bevacizumab-EU), on PK were investigated. Results Overall, 8632 serum bevacizumab concentrations from 351 patients in the PF-06439535 group and 354 patients in the bevacizumab-EU group were included in the analysis. A two-compartment model adequately described the combined data. Clearance (CL) and central volume of distribution (V 1) estimates were 0.0113 L/h and 2.99 L for a typical 71-kg female patient with NSCLC administered bevacizumab-EU. CL and V 1 increased with body weight and were higher in males than females even after accounting for differences in body weight. The 95% confidence intervals for the effect of drug product on CL and V 1 encompassed unity. Conclusions The population PK of PF-06439535 and bevacizumab-EU were well characterized by a two-compartment model. Covariate analysis did not reveal any appreciable differences between PK parameters for PF-06439535 and bevacizumab-EU in patients with NSCLC. Clinical trial registration ClinicalTrials.gov, NCT02364999.

show abstract

Section: Introductionmentioning

confidence: 74%

Population pharmacokinetic modeling of PF-06439535 (a bevacizumab biosimilar) and reference bevacizumab (Avastin®) in patients with advanced non-squamous non-small cell lung cancer

Sweeney

Cronenberger

2019

Cancer Chemother Pharmacol

View full text Add to dashboard Cite

show abstract

“…The numbers of subjects testing positive for antidrug antibodies were similarly low across treatment arms; none tested positive for neutralizing antibodies. The reporting of treatment-related adverse events in the PF-06439535 (15.2% of subjects), bevacizumab-EU (25.7%) and bevacizumab-US (18.2%) arms indicated comparable safety profiles between treatments [71].…”

Section: Bevacizumab Biosimilars: Considerations For Development and Apmentioning

confidence: 93%

“…The PK similarity of PF-06439535, bevacizumab-EU and bevacizumab-US, and between bevacizumab-EU and bevacizumab-US, following a single intravenous dose were compared in 102 healthy male subjects [71]. The three study drugs exhibited similar PK profiles, as the 90% CIs for the ratios of maximum serum concentration, area under the serum concertation-time curve from time zero to time of last quantifiable concentration and zero to infinity were all within 80.00-125.00% bioequivalence acceptance window for the comparisons of PF-06439535 to bevacizumab-EU or bevacizumab-US, and of bevacizumab-EU to bevacizumab-US.…”

Section: Bevacizumab Biosimilars: Considerations For Development and Apmentioning

confidence: 99%

Bevacizumab Biosimilars: Scientific Justification for Extrapolation of Indications

et al. 2018

View full text Add to dashboard Cite

The first biosimilar of bevacizumab was approved by the US FDA; other potential biosimilars of bevacizumab are in late-stage clinical development. Their availability offers opportunity for increased patient access across a number of oncologic indications. The regulatory pathway for biosimilar approval relies on the totality of evidence that includes a comprehensive analytical assessment, and a clinical comparability study in a relevant disease patient population. Extrapolation of indications for a biosimilar to other eligible indications held by the originator, in the absence of direct clinical comparison, frequently forms part of the regulatory judgment. Herein, we consider the evidence required to demonstrate biosimilarity for bevacizumab biosimilars, with particular focus on the rationale for extrapolation across oncologic indications. Bevacizumab (Avastin R ; Roche, Welwyn Garden City, UK; Genentech, CA, USA) is a monoclonal antibody directed against VEGF. It is approved in Europe and the USA for the treatment of a range of cancers, including metastatic or recurrent nonsquamous non-small-cell lung cancer (NSCLC), metastatic renal cell carcinoma, metastatic colorectal cancer (CRC), cervical cancer, and platinum-resistant or platinum-sensitive recurrent epithelial ovarian, fallopian tube and primary peritoneal cancers [1,2]. In addition, in the USA, Japan, and many other countries, bevacizumab is indicated for the treatment of patients with glioblastoma. In Europe, it is also authorized for use in metastatic breast cancer and in combination with erlotinib for the first-line treatment of advanced, metastatic nonsquamous NSCLC with EGF receptor-activating mutations [3]. Randomized Phase III trials have shown that progression-free survival (PFS) and/or overall survival (OS) in patients with these cancers is prolonged with treatment combining bevacizumab with standard chemotherapy (Table 1) [4][5][6][7][8][9][10][11][12]. Nonetheless, patient access to bevacizumab may be limited.Barriers to bevacizumab use stem from factors such as insurance coverage and cost of treatment, manufacturing and supply and uncertainty as to its cost-effectiveness in some clinical settings [13][14][15]. A survey conducted by the European Society of Medical Oncology Consortium found budget constraints, affordability and issues related to the manufacture and assured supply of the product were cited most frequently as reasons for access to bevacizumab to be considered suboptimal [13]. Oncologists who were surveyed in the USA, Europe and in some emerging market countries (Brazil, Mexico and Turkey) stated the major barriers to prescribing bevacizumab were the high out-of-pocket costs for patients and a lack of reimbursement. These barriers were commonly cited as reasons for reducing the number of drug treatment cycles that were planned for patients [15].Protein-based biologics, such as bevacizumab, are produced in living cells rather than by chemical synthesis, and are large and structurally complex [16]. Their structure and activity are in...

show abstract

“…PF-06439535 has followed a similar clinical program to ABP 215, first demonstrating PK equivalence and comparable safety to both US-sourced and EU-sourced reference bevacizumab in healthy males [40]. A Phase III trial is currently ongoing to assess the efficacy and safety of PF-06439535 in previously untreated patients with advanced nonsquamous nonsmall-cell lung cancer in combination with paclitaxel and carboplatin [41].…”

Section: • Clinical Trials Of Trastuzumab Biosimilarsmentioning

confidence: 99%

Clinical development of CT-P10 and other biosimilar cancer therapeutics

2017

View full text Add to dashboard Cite

Biosimilars are highly similar versions of approved biologic drugs that may confer equivalent efficacy at a reduced cost. Patents for several biological cancer therapeutics are past or approaching expiry, presenting an opportunity to increase affordability and global accessibility of key drugs through the development of biosimilars. To receive approval, a biosimilar must show no clinically meaningful differences from the reference product in terms of efficacy or safety. The first monoclonal antibody biosimilar cancer therapeutic to gain approval was CT-P10, a biosimilar of rituximab. Here, we review the oncology clinical development program for CT-P10, providing insights into the rationale for, and design of, CT-P10 clinical trials in patients with cancer. Trials of biosimilar cancer therapeutics in development are also discussed.

show abstract

A phase I pharmacokinetics study comparing PF-06439535 (a potential biosimilar) with bevacizumab in healthy male volunteers

Cited by 47 publications

References 1 publication

Population pharmacokinetic modeling of PF-06439535 (a bevacizumab biosimilar) and reference bevacizumab (Avastin®) in patients with advanced non-squamous non-small cell lung cancer

Population pharmacokinetic modeling of PF-06439535 (a bevacizumab biosimilar) and reference bevacizumab (Avastin®) in patients with advanced non-squamous non-small cell lung cancer

Bevacizumab Biosimilars: Scientific Justification for Extrapolation of Indications

Clinical development of CT-P10 and other biosimilar cancer therapeutics

Contact Info

Product

Resources

About