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  • BMJ  (2)
  • Alvarez, D.  (2)
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  • 1
    Online Resource
    Online Resource
    AB0285 RANDOMIZED, OPEN-LABEL, SINGLE-DOSE, PARALLEL-GROUP PHARMACOKINETIC STUDY OF PF-06410293, AN ADALIMUMAB BIOSIMILAR, BY SUBCUTANEOUS DOSING USING A PREFILLED SYRINGE OR A PREFILLED PEN IN HEALTHY SUBJECTS
    BMJ ; 2020
    In:  Annals of the Rheumatic Diseases Vol. 79, No. Suppl 1 ( 2020-06), p. 1441.2-1442
    Details
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 79, No. Suppl 1 ( 2020-06), p. 1441.2-1442
    Abstract: Similarity in efficacy, safety, and immunogenicity (IMG) of PF-06410293 (ADL-PF), an adalimumab (ADL) biosimilar, and reference ADL sourced from the European Union (ADL-EU), by subcutaneous (SC) injection using a prefilled syringe (PFS), have been demonstrated in a randomised controlled trial in patients with rheumatoid arthritis (RA) ( NCT02480153 ). Objectives: To determine if the pharmacokinetics (PK), safety and tolerability of ADL-PF were similar following a single SC dose by prefilled pen (PFP) or PFS in healthy subjects ( NCT02572245 ). Methods: In this phase 1, 2-arm study, healthy subjects, aged 18–55 years, were randomised (1:1) to receive ADL-PF (40 mg, SC) in the lower abdomen or upper anterior thigh by PFS or PFP. Primary endpoints were maximum observed serum concentration (C max ) and area under the serum concentration–time profile from time 0–2 weeks after dosing (AUC 0-2wk ). Safety, including injection-site reactions (ISRs), and secondary PK endpoints, were also assessed. Bioequivalence between ADL-PF administered by PFS or PFP device was demonstrated if the 90% confidence intervals (CIs) for the test/reference ratios of AUC 0-2wk and C max fell within the 80.00–125.00% pre-specified margin. Results: A total of 164 subjects, stratified by body weight were randomised and assigned to treatment; ADL-PF PFS (n=81) and PFP (n=83). Baseline characteristics were comparable between treatment arms. 163 subjects were included in the primary PK analysis. The concentration–time profiles were comparable between the ADL-PF PFS and PFP treatment arms, and were characterized by an increase in serum drug concentrations, with the C max achieved at approximately 6-7 days, followed by a multi-phasic decline in drug concentrations. The 90% CIs for test/reference ratios of the geometric means for the primary PK parameters fell within the pre-specified margin ( Table ). In total, 50 and 51 treatment-emergent adverse events (AEs) were reported in 31 (38.3%) and 29 subjects (34.9%), respectively, in the ADL-PF PFS and PFP groups. One subject experienced an unrelated serious AE in the ADL-PF PFS group. Injection-site pain was similar between treatment arms at all time points, and for the 2 injection-site locations. IMG testing was limited to subjects experiencing an ISR and/or rash AE, and a matched control group, with 11 (11/15; 73.3%) and 7 (7/15; 46.7%) subjects, respectively, testing anti-drug antibody (ADA)-positive. Amongst ADA-positive subjects, a majority (12/18) also tested positive for neutralising ADAs (7/11 [63.6%] and 5/7 [71.4%] subjects, respectively). Conclusion: This study demonstrated that the PK of ADL-PF was comparable following SC administration using either a PFS or PFP device. ADL-PF by PFS or PFP injection was well tolerated by healthy subjects, with the distribution of AEs, including ISRs, being similar between treatment arms. Table. Summary of Statistical Comparisons of PK Exposure Parameters between Test and Reference Treatments (PK Analysis Set) PK parameter (units) Adjusted geometric means Ratioa,b 90% CI for ratiob ADL-PF PFP (test) ADL-PF PFS (reference) C max (μg/mL) 4.45 4.13 107.74 99.16–117.06 AUC 0-2wk (μg•hr/mL) 1150 1100 104.89 95.76–114.89 AUC T (μg•hr/mL) 2040 2100 97.23 86.75 – 108.98 AUC 0-inf (μg•hr/mL) 2200 2150 102.27 91.12 – 114.78 T max (hr) c 142 (45.4, 336) 166 (47.7, 674) a (test/reference) of adjusted means. b Ratios and 90% CIs are expressed as percentages. c Median (range). ADL-PF, PF-06410293; AUC, area under the serum concentration–time profile; AUC 0-2wk , AUC from time 0–2 weeks after dosing; AUC inf , AUC from time 0 extrapolated to infinity; AUC T , AUC from time 0 to the time point of the last quantifiable concentration; C max , maximum observed serum concentration; CI, confidence interval; h, hour(s); PK, pharmacokinetic(s); PFP, prefilled pen; PFS, prefilled syringe; T max , time of maximum serum concentration. Acknowledgments: Medical writing support was provided by Iain McDonald of Engage Scientific Solutions. The study was funded by Pfizer. Disclosure of Interests: Donna Cox Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Daniel Alvarez Shareholder of: Pfizer, Employee of: Pfizer, Amy Bock Shareholder of: Pfizer, Employee of: Pfizer, Carol Cronenberger Shareholder of: Pfizer, Employee of: Pfizer
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    URL: Article
    DOI: 10.1136/annrheumdis-2020-eular.454
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 1481557-6
    Location Call Number Limitation Availability
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  • 2
    Online Resource
    Online Resource
    AB0289 EFFICACY, SAFETY AND IMMUNOGENICITY IN PATIENTS WITH RHEUMATOID ARTHRITIS COMPARING PF-06410293 (ADL-PF), AN ADALIMUMAB (ADL) BIOSIMILAR, AND REFERENCE ADL: RESULTS FROM WEEK 26–52 OF A DOUBLE-BLIND, RANDOMISED PHASE 3 STUDY INCLUDING PATIENTS WHO SWITCHED FROM ADL-PF TO REFERENCE ADL AT WEEK 26
    BMJ ; 2020
    In:  Annals of the Rheumatic Diseases Vol. 79, No. Suppl 1 ( 2020-06), p. 1443.1-1444
    Details
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 79, No. Suppl 1 ( 2020-06), p. 1443.1-1444
    Abstract: PF-06410293 (ADL-PF) is an adalimumab biosimilar approved for the treatment of several inflammatory and autoimmune indications. 1 The efficacy, safety and immunogenicity of ADL-PF and reference adalimumab sourced from the European Union (ADL-EU) in patients with rheumatoid arthritis (RA) have been demonstrated to be similar in a randomised controlled trial up to 26 weeks (wks; treatment period 1 [TP1]). 2 Objectives: To evaluate the efficacy, safety and immunogenicity of ADL-PF and ADL-EU in patients with moderate to severe RA on longer-term treatment, and following a treatment switch from ADL-EU to ADL-PF in a subset of patients. Methods: This multinational, randomised, double-blind, parallel-group study compared ADL-PF and ADL-EU in essentially biologic-naïve patients with active RA despite methotrexate (MTX) ( NCT02480153 ). In TP1, patients were randomised (1:1) to ADL-PF or ADL-EU (40 mg subcutaneous injection every 2 wks) for 26 wks while continuing MTX (10–25 mg/wk). The primary endpoint was achievement of American College of Rheumatology response (ACR20) at Wk 12. At Wk 26, the start of treatment period 2 (TP2), patients receiving ADL-EU were blindly re-randomised (1:1) to remain on ADL-EU or switch to ADL-PF for 26 wks while patients receiving ADL-PF continued treatment in a blinded manner. Secondary efficacy endpoints at Wks 26, 30, 36, 44 and 52 (ACR20/50/70, European League Against Rheumatism [EULAR] response, Disease Activity Score [DAS] 28-4[CRP] 〈 2.6 and ACR/EULAR defined remission), safety events and percentage of patients with anti-drug antibodies (ADA) were assessed. Results: In TP1, 597 patients were randomised to ADL-PF (n=297) or ADL-EU (n=300). At Wk 26, 552 patients were re-randomised for TP2 (continued ADL-PF, n=283; continued ADL-EU, n=135; switched from ADL-EU to ADL-PF, n=134). Patients who demonstrated at least minimal efficacy continued in TP2. Observed ACR20 rates were comparable between treatment groups at all visits during TP2 ( Figure ). Other measures of deep response (ACR70, EULAR good response, DAS28-4(CRP) 〈 2.6 and ACR/EULAR defined remission) showed maintained efficacy during TP2 in all treatment groups. Incidences of treatment-emergent adverse events were comparable between treatment groups ( Table ). Overall, incidences of ADA through Wk 52 were comparable between treatment groups (47.3%, 54.1% and 45.9% for patients who continued ADL-PF, continued ADL-EU or switched from ADL-EU to ADL-PF, respectively). In patients who switched from ADL-EU to ADL-PF compared with patients who continued ADL-EU, the increase in ADA incidence over TP2 was 0.8% (from 45.1% to 45.9%) versus 6.7% (from 47.4% to 54.1%), respectively. Conclusion: TP2 results demonstrated comparable efficacy, safety and immunogenicity between ADL-PF and ADL-EU was maintained up to Wk 56 and was unaffected by a blinded switch from ADL-EU to ADL-PF at Wk 26. References: [1]Pfizer Inc, 2019. http://labeling.pfizer.com/ShowLabeling.aspx?id=12780 [2]Fleischmann RM et al, Arthritis Res Ther 2018;20:178. Table. All-causality TEAEs: Treatment Period 2 (Safety population) Continued ADL-PF (n=283) Continued ADL-EU (n=135) Switched from ADL-EU to ADL-PF (n=133) Number of AEs 243 112 100 Patients with events, n (%)  AEs 123 (43.5) 60 (44.4) 51 (38.3)  Serious AEs 4 (1.4) 6 (4.4) 3 (2.3)  ≥ Grade 3 AEs 7 (2.5) 7 (5.2) 4 (3.0) TEAEs leading to treatment discontinuation 6 (2.1) 8 (5.9) 2 (1.5) Deaths 0 0 0 ADL-EU, adalimumab sourced from the European Union; ADL-PF, adalimumab biosimilar PF-06410293; AE, adverse event; TEAE, treatment-emergent AE. Acknowledgments: Medical writing support, provided by Jacqui Oliver of Engage Scientific Solutions. The study was funded by Pfizer. Disclosure of Interests: Roy Fleischmann Grant/research support from: AbbVie, Akros, Amgen, AstraZeneca, Bristol-Myers Squibb, Boehringer, IngelhCentrexion, Eli Lilly, EMD Serono, Genentech, Gilead, Janssen, Merck, Nektar, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Samsung, Sandoz, Sanofi Genzyme, Selecta, Taiho, UCB, Consultant of: AbbVie, ACEA, Amgen, Bristol-Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, Novartis, Pfizer, Sanofi Genzyme, UCB, Daniel Alvarez Shareholder of: Pfizer, Employee of: Pfizer, Amy Bock Shareholder of: Pfizer, Employee of: Pfizer, Carol Cronenberger Shareholder of: Pfizer, Employee of: Pfizer, Ivana Vranic Shareholder of: Pfizer, Employee of: Pfizer, Wuyan Zhang Shareholder of: Pfizer, Employee of: Pfizer, Rieke Alten Grant/research support from: Pfizer, Galapagos, Galapagos NV, Gilead, Gilead Sciences, Inc., Novartis, Consultant of: Pfizer, Speakers bureau: Pfizer
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
    URL: Article
    DOI: 10.1136/annrheumdis-2020-eular.279
    RVK:
    XA 10000
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 1481557-6
    Location Call Number Limitation Availability
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    Online Resource
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