Repatha: which risks did reviewers probe?

“Since the interpretation of the TDAR relies on comparisons between groups of KLH-naïve animals, these animals were excluded from the TDAR analysis; the results were no longer statistically significant.”

“Measurable evolocumab serum concentrations were observed in the infant monkeys at birth at comparable levels to maternal serum, indicating that evolocumab, like other IgG antibodies, crosses the placental barrier.”

“Of note, humoral immune suppression was observed in infant monkeys exposed in utero to another drug in this class (alirocumab); effects on humoral immunity were not evaluated in the developmental studies for the evolocumab program.”

“In hamster, evolocumab was not immunogenic. In Cynomolgus monkey the incidence of anti-evolocumab antibodies (antidrug antibodies, ADA) was not higher than 10%. In some animals these ADA were neutralising.”

“In a pool of placebo- and active-controlled clinical trials, 0.3% (48 out of 17,992) of adult patients treated with at least one dose of REPATHA tested positive for the development of binding antibodies. Patients whose sera tested positive for binding antibodies were further evaluated for neutralizing antibodies; none of the patients tested positive for neutralizing antibodies.”