PF-05280586 US Randomised, Patients with 90% CI of ratios for No observed [13] Rituximab (Rituxan) active Cmax, AUCT, AUC0–∞ differences among (Pfizer) and EU two-dose, rheumatoid and AUC2-90% CIs of treatment groups in the (MabThera) arthritis on a the geometric mean incidence of ADAs, time Rituximab study background ratios of AUClast, of ADA emergence or 1000mg (1:1:1) of AUCinf and Cmax were ADA titres. No samples methotrexate within the prespecified were positive for and acceptance criteria of antibodies. inadequate 80-125%. Thirteen patients response to No observed tested positive for anti-TFN differences among ADAs at baseline (n=4, therapy groups in the CD19+ n=6 and n=3 receiving (n=220; B cell count versus time PF-05280586, 50M/170F; profile and the rituximab-EU and 198PPP) parameters determined rituximab-US, (B cell AUClast, Cmin, respectively). Of these, Tmin and eight (n=4, n=3 and τ). n=1, respectively) tested negative in all subsequent post-dose samples. The remaining 5 patients tested positive for ADAs at at least one post-dose time-point. A total of 26 patients tested positive for ADAs at at least one post-dose time (n=7, n=10 and n=9 receiving PF-05280586, rituximab-EU and rituximab-US, respectively). Of these, 22 patients did not have detectable levels of ADAs until Day 85 or later (n=6, n=7 and n=9, respectively). Potential biosimilar medicines that demonstrate appropriate pharmacokinetic parameters in phase I studies are then subject to phase III clinical trials to evaluate efficacy and safety outcomes in comparison with the reference product. Within the update period there were three reports describing the clinical outcomes obtained in phase III clinical trials of potential biosimilar medicines.
PF-05280586 Rituximab (Pfizer) US (Rituxan) and EU (MabThera) Rituximab 1000mg Randomised, two-dose, study (1:1:1) Patients with active rheumatoid arthritis on a background of methotrexate and inadequate response to anti-TFN therapy (n=220; 50M/170F; 198PPP) 90% CI of ratios for Cmax, AUCT, AUC0–∞ and AUC2-90% CIs of the geometric mean ratios of AUClast, AUCinf and Cmax were within the prespecified acceptance criteria of 80-125%. No observed differences among groups in the CD19+ B cell count versus time profile and the parameters determined (B cell AUClast, Cmin, Tmin and τ). No observed differences among treatment groups in the incidence of ADAs, time of ADA emergence or ADA titres. No samples were positive for antibodies. Thirteen patients tested positive for ADAs at baseline (n=4, n=6 and n=3 receiving PF-05280586, rituximab-EU and rituximab-US, respectively). Of these, eight (n=4, n=3 and n=1, respectively) tested negative in all subsequent post-dose samples. The remaining 5 patients tested positive for ADAs at at least one post-dose time-point. A total of 26 patients tested positive for ADAs at at least one post-dose time (n=7, n=10 and n=9 receiving PF-05280586, rituximab-EU and rituximab-US, respectively). Of these, 22 patients did not have detectable levels of ADAs until Day 85 or later (n=6, n=7 and n=9, respectively). [13] Potential biosimilar medicines that demonstrate appropriate pharmacokinetic parameters in phase I studies are then subject to phase III clinical trials to evaluate efficacy and safety outcomes in comparison with the reference product. Within the update period there were three reports describing the clinical outcomes obtained in phase III clinical trials of potential biosimilar medicines.
biosimilars-literature-review-december-2016-update.docx