Afuco™ Anti-Human FGF23 ADCC Recombinant Antibody (KRN23), ADCC Enhanced (CAT#: AFC-268CL)

Figure 1 Effect of i.v. and s.c administration of KRN23 on TmP/GFR, serum Pi, and 1,25(OH)2D compared with placebo.

(A and B) TmP/GFR; (C and D) serum Pi; and (E and F) 1,25(OH)2D. For the i.v. cohorts, six profiles are shown for panels A, C, and E: placebo (gray), 0.003 (yellow), 0.01 (red), 0.03 (green), 0.1 (blue), and 0.3 mg/kg (black). For s.c. cohorts, five profiles are shown for panels B, D, and F: placebo (gray), 0.1 (blue), 0.3 (black), 0.6 (pink), and 1 mg/kg (brown). Data are presented as the mean ± SEM.

Carpenter, T. O., Imel, E. A., Ruppe, M. D., Weber, T. J., Klausner, M. A., Wooddell, M. M., ... & Insogna, K. L. (2014). Randomized trial of the anti-FGF23 antibody KRN23 in X-linked hypophosphatemia. The Journal of clinical investigation, 124(4), 1587-1597.

Figure 2 Mean serum KRN23 concentration increased as mean dose increased.

Mean serum KRN23 concentration over time (A) and dose proportionality between mean log KRN23 AUCn and mean log dose during the 4 dosing intervals (B). Error bars represent standard deviation (SD). The mean ± SD dose was 0.05 ± 0.0, 0.10 ± 0.01, 0.28 ± 0.06, and 0.48 ± 0.16 mg/kg for dosing intervals 1, 2, 3, and 4, respectively. N = 27 for dosing intervals 1 to 3 and n = 26 for dosing interval 4.

Zhang,X.,Imel,E.A.,Ruppe,M.D.,Weber,T.J.,Klausner,M A.,Ito,T.,& Insogna, K. (2016). Pharmacokinetics and pharmacodynamics of a human monoclonal anti-FGF23 antibody (KRN23) in the first multiple ascending-dose trial treating adults with X-linked hypophosphatemia. The Journal of Clinical Pharmacology, 56(2), 176-185.

Figure 3 Relationship of pharmacokinetic and bone marker change from baseline.

(A) BALP; (B) P1NP; (C) Osteocalcin; (D) CTx; (E) NTx/creatinine. AUCn, area under the KRN23 serum concentration–time curve; AUECn, area under the effect concentration–time curve for bone marker change from baseline during interval n (n = 1, 2, 3, or 4); R, Pearson correlation coefficient.

Zhang,X.,Imel,E.A.,Ruppe,M.D.,Weber,T.J.,Klausner,M A.,Ito,T.,& Insogna, K. (2016). Pharmacokinetics and pharmacodynamics of a human monoclonal anti-FGF23 antibody (KRN23) in the first multiple ascending-dose trial treating adults with X-linked hypophosphatemia. The Journal of Clinical Pharmacology, 56(2), 176-185.

Figure 4 Pharmacodynamic (PD) profiles over 4 dosing intervals (left) and relationship of PK and PD parameters (right).

(A and B) Serum calcium; (C and D) serum PTH; (E and F) 2-hour urine calcium/creatinine ratio; (G and H) 24-hour urine calcium. AUCn: area under the KRN23 serum concentration–time curve; AUECn, area under the effect concentration–time curve for PD change from baseline during interval n (n = 1, 2, 3, or 4); R, Pearson correlation coefficient.

Zhang,X.,Imel,E.A.,Ruppe,M.D.,Weber,T.J.,Klausner,M A.,Ito,T.,& Insogna, K. (2016). Pharmacokinetics and pharmacodynamics of a human monoclonal anti-FGF23 antibody (KRN23) in the first multiple ascending-dose trial treating adults with X-linked hypophosphatemia. The Journal of Clinical Pharmacology, 56(2), 176-185.