Vyndaqel: genotox, carcinogenicity and repro: done or skipped?

“Fx-1006A was negative for genotoxicity in an in vitro bacterial reverse mutation assay, an in vitro chromosomal aberration assay in human lymphocytes, and an in vivo rat micronucleus assay.”

“Carcinogenicity were evaluated in Tg.rasH2 transgenic mice dosed at 10, 30, or 90 mg/kg/day for 26 weeks and in Sprague Dawley rats dosed at 3, 10 or 30 mg/kg/day for 2 years. Both studies were considered adequate and found to be negative for increases in tumor findings with the Executive CAC’s concurrence.”

“Reduced survival, birth weight, postweaning body weight, delayed male sexual maturity, and impaired learning and memory were observed in the offspring of dams dosed at 15 mg/kg/day.”

“In the core GLP battery of safety pharmacology studies, tafamidis meglumine had no effects on the central nervous, cardiovascular, and pulmonary systems.”

“Fx-1006A was negative for genotoxicity in an in vitro bacterial reverse mutation assay, an in vitro chromosomal aberration assay in human lymphocytes, and an in vivo rat micronucleus assay.”

“Fx-1006A was negative for genotoxicity in an in vitro bacterial reverse mutation assay, an in vitro chromosomal aberration assay in human lymphocytes, and an in vivo rat micronucleus assay.”

“Fx-1006A was negative for genotoxicity in an in vitro bacterial reverse mutation assay, an in vitro chromosomal aberration assay in human lymphocytes, and an in vivo rat micronucleus assay.”

“Carcinogenicity were evaluated in Tg.rasH2 transgenic mice dosed at 10, 30, or 90 mg/kg/day for 26 weeks and in Sprague Dawley rats dosed at 3, 10 or 30 mg/kg/day for 2 years. Both studies were considered adequate and found to be negative for increases in tumor findings with the Executive CAC’s concurrence.”

“Carcinogenicity were evaluated in Tg.rasH2 transgenic mice dosed at 10, 30, or 90 mg/kg/day for 26 weeks and in Sprague Dawley rats dosed at 3, 10 or 30 mg/kg/day for 2 years. Both studies were considered adequate and found to be negative for increases in tumor findings with the Executive CAC’s concurrence.”

“In a definitive GLP hERG assay, tafamidis meglumine stimulated hERG current by (mean ± standard error of the mean) 0.5% at 1 μM, 4.7% at 10 μM, and 9.3% at 30 μM and inhibited hERG current by 5.4% at 3 μM, versus 0.1% in control. An IC50 could not be calculated, however no clinically relevant effect on hERG current was apparent.”