RT Journal Article
SR Electronic
T1 MEMP1972A, an anti-M1 prime monoclonal antibody, reduces serum IgE in healthy and allergic rhinitis subjects
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P4831
VO 40
IS Suppl 56
A1 Heleen Scheerens
A1 Wendy Putnam
A1 Yanan Zheng
A1 Yehong Wang
A1 Sofia Mosesova
A1 Romeo Maciuca
A1 Charlene Liao
A1 Lawren Wu
A1 John Matthews
A1 Jeffrey Harris
YR 2012
UL http://erj.ersjournals.com/content/40/Suppl_56/P4831.abstract
AB Background: MEMP1972A, a humanized monoclonal antibody specific for the M1 prime epitope of membrane IgE, depletes M1 prime-expressing IgE-switched B cells, IgE memory B cells and IgE plasmablasts. MEMP1972A is in development for the treatment for allergic asthma.Aim: To evaluate the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of MEMP1972A in healthy and allergic rhinitis (AR) subjects.Methods: Two Phase I, randomized, controlled trials investigated the safety, tolerability, PK and PD of MEMP1972A in (1) healthy adults (n=31 MEMP1972A, n=14 placebo [PB]) and (2) AR subjects (n=24 MEMP1972A, n=12 PB [NCT01160861]). In healthy adults, MEMP1972A was given as single escalating doses of 0.003–5 mg/kg intravenous (IV) or 3 mg/kg subcutaneous (SC). In AR subjects, monthly doses were given for 3 months at 1.5 and 5 mg/kg IV and 3 mg/kg SC.Results: MEMP1972A was well tolerated, and the exposure of serum MEMP1972A was dose proportional. Following IV administration, the mean terminal half-life of MEMP1972A was 20–21 days and mean clearance was 2.2–2.7 mL/day/kg. MEMP1972A administration led to a dose dependent reduction in serum IgE in both studies. In healthy adults, a single dose of MEMP1972A at 3 and 5 mg/kg IV significantly reduced serum IgE by ∼25% relative to baseline at Day 85, with no significant reductions observed in the PB, lower IV or 3 mg/kg SC cohorts. Monthly doses of MEMP1972A at 5 mg/kg IV or 3 mg/kg SC in AR subjects reduced serum IgE by ∼25% relative to baseline at Day 85. Serum IgE reductions were sustained for 6 months.Conclusion: MEMP1972A was well tolerated and reduced serum IgE in adults with or without allergic disease.