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

“Genetic toxicity studies have not been conducted with anifrolumab. Genetic toxicity studies are generally not applicable for biotechnology-derived pharmaceuticals such as anifrolumab, as discussed in the ICH S6(R1) guidance document.”

“Carcinogenicity studies with anifrolumab were not conducted. Anifrolumab does not bind to murine IFNAR1 and does not inhibit the biological activity of murine IFN-α.”

“There was no evidence of anifrolumab-fnia related maternal toxicity, embryo-fetal toxicity, or post-natal developmental effects.”

“No stand-alone safety pharmacology studies were conducted with anifrolumab. The effect of anifrolumab on the CV system was evaluated in a GLP-compliant 39-week general IV toxicity study in monkeys (Study# 7140-129).”

“Genetic toxicity studies have not been conducted with anifrolumab. Genetic toxicity studies are generally not applicable for biotechnology-derived pharmaceuticals such as anifrolumab, as discussed in the ICH S6(R1) guidance document.”

“Genetic toxicity studies have not been conducted with anifrolumab. Genetic toxicity studies are generally not applicable for biotechnology-derived pharmaceuticals such as anifrolumab, as discussed in the ICH S6(R1) guidance document.”

“Genetic toxicity studies have not been conducted with anifrolumab. Genetic toxicity studies are generally not applicable for biotechnology-derived pharmaceuticals such as anifrolumab, as discussed in the ICH S6(R1) guidance document.”

“Instead, a weight of evidence approach consisting of data from chronic toxicity studies with anifrolumab and literature data was presented to address the risk of carcinogenicity.”

“Based on the weight of evidence, treatment with anifrolumab is likely associated with an increased carcinogenicity risk that has been followed throughout the clinical development programme and addressed in the RMP (see Section 2.7), and thus, no further animal studies are necessary (SmPC section 5.3).”

“Electrocardiography (ECG) parameters and blood pressure (BP) parameters were measured once during the predose phase, on Days 3 and 276 of the dosing phase, and on Day 83 of the recovery phase for these animals after they were anesthetized with ketamine. No drug-related adverse CV findings were noted.”