031: Pharmacokinetic Drug Interaction Between Nipocalimab & Fremanezumab in Healthy Subjects

Statement of Purpose: Nipocalimab is a fully human immunoglobulin (Ig) G1 monoclonal antibody (mAb) which selectively binds, saturates, and blocks the IgG binding site on endogenous neonatal fragment crystallizable receptor (FcRn). Nipocalimab is currently in clinical development for the treatment of myasthenia gravis and other allo- and auto-antibody related diseases. By block IgG recycling, nipocalimab could impact the pharmacokinetics (PK) and efficacy of Fc-containing IgG-based mAbs. To test this hypothesis, a Phase 1 study (MOM-M281-008) was conducted to determine the effect of nipocalimab on the PK of a representative mAb, fremanezumab (a humanized IgG2Δa/kappa mAb).

Description of Methods & Materials: Study MOM-M281-008 was a Phase 1, open-label, parallel, three-way, drug interaction study to assess the effect of nipocalimab co-administration or offset-administration on the PK of fremanezumab in healthy subjects.

Data & Results: When co-administered with nipocalimab at the same day/time, fremanezumab C_max decreased 42% and AUC_inf decreased 66% compared to fremanezumab dosing alone. When co-administered with nipocalimab on Day 15 (nipocalimab administered 14 days after fremanezumab dosing), fremanezumab C_max remained unchanged but AUC_inf decreased 54% compared to fremanezumab dosing alone.

Interpretation, Conclusion or Significance: The clinical data are consistent with nipocalimab’s mechanism-of-action and confirm the hypothesis that nipocalimab significantly reduces the PK of IgG-based mAbs with an Fc portion. Hence, nipocalimab may reduce the efficacy of such therapeutics in the case of simultaneous co-administration, and when nipocalimab is dosed 2 weeks after fremanezumab. This study is part of an overall nipocalimab drug-drug interaction strategy that will inform various nipocalimab indications.

Disclosures: All authors are or were employees of Janssen Pharmaceuticals and may hold stock or stock options in Johnson & Johnson.