Brian Maas (United States of America)

MSD Quantitative Pharmacology and Pharmacometrics
Dr Brian Maas is an associate principal scientist in the quantitative pharmacology and pharmacometrics group at Merck Sharp & Dohme. Brian graduated from the University of Florida in 2015 with his Doctor of Pharmacy. He went on to complete a clinical pharmacology and pharmacometrics fellowship at the University of North Carolina, with a focus on tissue distribution of antiretrovirals and pharmacokinetics of monoclonal antibodies. Since joining Merck Sharp and Dohme in 2017, Brian has served as the clinical pharmacology lead for several candidate compounds for RSV, HIV, and COVID-19. He is interested in applying mathematical models across different modalities to streamline development and bring drugs to patients in need.

Author Of 1 Presentation

 Conference Calendar

PHARMACOKINETICS AND SERUM NEUTRALIZING ACTIVITY FROM A PHASE 1B/2A STUDY IN INFANTS SUPPORT MODEL-BASED EFFICACY PREDICTIONS FOR MK-1654, AN RSV NEUTRALIZING MONOCLONAL ANTIBODY

Date
Wed, 11.05.2022
Session Time
10:00 - 11:10
Session Type
Oral Presentations Session
Session Name
0255 - ORAL PRESENTATION SESSION 01: Respiratory Infections (ID 89)
Room
NIKOS SKALKOTAS HALL
Presenter
Lecture Time
10:52 - 11:02

Abstract

Backgrounds:

MK-1654 is an investigational RSV-neutralizing monoclonal antibody in development for the prevention of medically-attended lower respiratory tract infection (MALRI) in infants. This work summarizes interim pharmacokinetic (PK) and serum neutralizing antibody (SNA) results in infants. The efficacy of MK-1654 is also predicted using a published model.

Methods

This phase 1b/2a double-blind, randomized, placebo-controlled, study evaluated the safety, tolerability, PK, and SNA of MK-1654 in pre-term (born 29-35 weeks gestational age) and full-term infants. Participants (n=180) 2 weeks to 8 months of age were randomized in a 4:1 ratio within five separate panels (pre-term: 20, 50, 75 or 100-mg, full-term: 100mg) to receive a single intramuscular dose of MK-1654 or placebo. Blood samples were collected to quantify MK-1654 serum concentrations and SNA titers. A preliminary population PK (popPK) model was developed to describe PK of MK-1654 in infants. The efficacy of MK-1654 was predicted using clinical trial simulations which were based on the popPK model and a published model-based meta-analysis.

Results:

Concentration data from 111 pre-term infants and 32 full-term infants through at least 150 days post-administration were available. The pharmacokinetics of MK-1654 were best characterized by a linear two-compartment popPK model with first-order absorption and elimination. Clearance and volume of distribution (Vd) were scaled allometrically using time-varying body weight. Age was also a covariate on Vd. The half-life of MK-1654 was approximately 42 days. A linear relationship was observed between increasing concentrations of MK-1654 and increasing SNA. Clinical trial simulations predict that a single dose of ≥75 mg of MK-1654 will provide >75% efficacy for the prevention of RSV MALRI for a duration of 5 months in infants.

Conclusions/Learning Points:

These findings support the continued evaluation of MK-1654 in ongoing Phase 3 studies.

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Presenter of 1 Presentation

 Conference Calendar

PHARMACOKINETICS AND SERUM NEUTRALIZING ACTIVITY FROM A PHASE 1B/2A STUDY IN INFANTS SUPPORT MODEL-BASED EFFICACY PREDICTIONS FOR MK-1654, AN RSV NEUTRALIZING MONOCLONAL ANTIBODY

Date
Wed, 11.05.2022
Session Time
10:00 - 11:10
Session Type
Oral Presentations Session
Session Name
0255 - ORAL PRESENTATION SESSION 01: Respiratory Infections (ID 89)
Room
NIKOS SKALKOTAS HALL
Presenter
Lecture Time
10:52 - 11:02

Abstract

Backgrounds:

MK-1654 is an investigational RSV-neutralizing monoclonal antibody in development for the prevention of medically-attended lower respiratory tract infection (MALRI) in infants. This work summarizes interim pharmacokinetic (PK) and serum neutralizing antibody (SNA) results in infants. The efficacy of MK-1654 is also predicted using a published model.

Methods

This phase 1b/2a double-blind, randomized, placebo-controlled, study evaluated the safety, tolerability, PK, and SNA of MK-1654 in pre-term (born 29-35 weeks gestational age) and full-term infants. Participants (n=180) 2 weeks to 8 months of age were randomized in a 4:1 ratio within five separate panels (pre-term: 20, 50, 75 or 100-mg, full-term: 100mg) to receive a single intramuscular dose of MK-1654 or placebo. Blood samples were collected to quantify MK-1654 serum concentrations and SNA titers. A preliminary population PK (popPK) model was developed to describe PK of MK-1654 in infants. The efficacy of MK-1654 was predicted using clinical trial simulations which were based on the popPK model and a published model-based meta-analysis.

Results:

Concentration data from 111 pre-term infants and 32 full-term infants through at least 150 days post-administration were available. The pharmacokinetics of MK-1654 were best characterized by a linear two-compartment popPK model with first-order absorption and elimination. Clearance and volume of distribution (Vd) were scaled allometrically using time-varying body weight. Age was also a covariate on Vd. The half-life of MK-1654 was approximately 42 days. A linear relationship was observed between increasing concentrations of MK-1654 and increasing SNA. Clinical trial simulations predict that a single dose of ≥75 mg of MK-1654 will provide >75% efficacy for the prevention of RSV MALRI for a duration of 5 months in infants.

Conclusions/Learning Points:

These findings support the continued evaluation of MK-1654 in ongoing Phase 3 studies.

Hide