Safety, tolerability and pharmacokinetics of subcutaneous and intravenous anifrolumab in healthy volunteers.

OBJECTIVES

To compare the pharmacokinetics (PK), safety and tolerability of subcutaneous (SC) and intravenous anifrolumab, an anti-type I interferon receptor monoclonal antibody in development for SLE, in healthy volunteers.

METHODS

In this Phase I randomised, placebo-controlled study, 30 adults were assigned to three treatment cohorts (anifrolumab 300 mg SC (n=6), anifrolumab 300 mg intravenous (n=6), anifrolumab 600 mg SC (n=6)) and placebo (n=4/cohort). Serial blood samples were collected up to Day 84 to measure anifrolumab concentrations and antidrug antibodies (ADAs). PK parameters were estimated by noncompartmental analysis.

RESULTS

Maximum serum concentrations in SC cohorts occurred after 4-7 days. Anifrolumab serum concentrations were below the limit of detection in all individuals by Day 84. Exposure to SC anifrolumab increased dose proportionally from 300 mg to 600 mg based on area under the serum concentration-time curve. Anifrolumab 300 mg SC exposure reached 87% of the intravenous exposure. Anifrolumab 300 mg SC and placebo administration elicited minimal injection-site reactions. Transient injection-site induration occurred in five of six individuals after anifrolumab 600 mg SC and two of four individuals after placebo. Transient, mild to moderate injection-site induration and pruritus occurred simultaneously in two of six individuals after anifrolumab 600 mg SC. Adverse events were reported by 50% (n=9) of anifrolumab-treated individuals and 33% (n=4) of placebo-treated individuals. ADAs were detected in only one individual in the anifrolumab 300-mg intravenous group at the Day 84 assessment.

CONCLUSION

Anifrolumab 300-mg SC exposure was 87% of intravenous administration, with single SC anifrolumab administrations well tolerated in healthy volunteers.