Daclizumab HYP a new kid on the block

Othman AA, Tran JQ, Tang MT, Dutta S.Population Pharmacokinetics of Daclizumab High-Yield Process in Healthy Volunteers: Integrated Analysis of Intravenous and Subcutaneous, Single- and Multiple-Dose Administration. Clin Pharmacokinet. 2014 Sep 12. [Epub ahead of print]

BACKGROUND AND OBJECTIVE:Daclizumab is a humanized monoclonal antibody that blocks the α-subunit of the interleukin-2 receptor with demonstrated benefits in the treatment of multiple sclerosis. The present work aimed to characterize the pharmacokinetics of daclizumab high-yield process (HYP) in healthy volunteers.
METHODS:Three double-blind, randomized, placebo-controlled, phase I studies evaluated the pharmacokinetics of daclizumab HYP in healthy volunteers following single subcutaneous administration (50, 150, or 300 mg), multiple subcutaneous administrations (100 or 200 mg biweekly with a 200 mg loading dose), or single intravenous administration (200 or 400 mg). Measurable serum concentrations (n = 925) from 70 subjects treated with daclizumab HYP in the three studies were analyzed using non-linear mixed-effects modeling.
RESULTS:A two-compartment model with a first-order absorption and elimination adequately described daclizumab HYP pharmacokinetics. Daclizumab HYP clearance, inter-compartmental clearance, and central and peripheral volumes of distribution were 10 mL/h, 44 mL/h, 3.89 L, and 2.52 L, respectively, scaled by [bodyweight (kg)/70] with 0.54 and 0.64 exponents for clearance and volume parameters, respectively. Lag-time, mean absorption time, and absolute bioavailability (100-300 mg) for subcutaneous administration were 2 h, 4.6 days, and 84 %, respectively. Bodyweight explained only ~20 % of daclizumab HYP pharmacokinetic variability. With this limited dataset, sex, age, race, or presence of antibodies did not correlate with daclizumab HYP clearance. The estimated effective half-life was 21-25 days. The developed model was robust in bootstrap evaluation and predicted the data adequately in stochastic simulations.
CONCLUSIONS:Daclizumab HYP is characterized by slow clearance, linear pharmacokinetics (at doses ≥100 mg), high subcutaneous bioavailability, and a half-life suitable for monthly administration.

This is data of early studies looking at how people handle daclizumab (an antibody that blocks T cell function and augments a subset of Natural killer cells. They found they could get the dose for a once a month dosing. The results of the phase III trial inMS was presented at ECTRIMS2014 and there was a significantly better effect than using beta interferon. The major side effect was skin reactions at the site of injections, which could be treated with steroids. So this is going to be the next new MS drug. We will report on this as the data is published