Further Immunomodulatory Evidence for Daclizumab HYP in Relapsing-Remitting MS

VANCOUVER, BC—Data from patients with relapsing-remitting multiple sclerosis (MS) who received the humanized monoclonal antibody daclizumab high-yield process (DAC HYP) “extend previous observations” on the agent’s rapid pharmacodynamic effects on CD56^bright natural killer (NK) cells and regulatory T-cells (Tregs) at treatment initiation, providing additional evidence for an immunomodulatory effect, investigators reported at the 68^th AAN Annual Meeting.

“Decreases in total and differential lymphocyte counts during DAC HYP treatment were modest and reversible upon treatment discontinuation,” reported Sami Fam, PhD, of Biogen in Cambridge, MA, and coauthors, in a poster presentation. “Total lymphocyte counts returned to baseline levels ~8–12 weeks after the last dose of DAC HYP. The CD4+/CD8+ ratio remained stable.”

“The absence of profound depletion of total lymphocytes and CD4+ and CD8+ T cells during treatment and the reversibility of the changes in cell counts examined, provide further evidence of the targeted immunomodulatory mechanism of action of DAC HYP in MS,” they noted.

Daclizumab HYP has been shown to modulate interleukin-2 receptor signaling selectively, which leads to inhibitory effects on pro-inflammatory effector T-cell activities and increased immunoregulatory CD56^bright NK cell numbers.

To evaluate effects of daclizumab HYP 150mg on total and differential lymphocyte populations in patients with relapsing-remitting MS, CD56^bright NK cells, Tregs, CD4⁺, and CD8⁺ T-cells were assessed using validated flow cytometry assays in patients who received daclizumab HYP 150mg in the SELECT and SELECTION trials comprising the SELECT Trilogy.

After completing SELECT, 55 patients were randomly assigned to a 24-week washout period followed by reinitiation of daclizumab HYP 150mg and completed treatment in SELECTION. Fifty-seven were randomly assigned to continue DAC HYP 150mg SC for two consecutive years, the coauthors wrote.

“At the end of the washout period, mean total lymphocyte counts were not notably different from baseline,” they noted. “The mean CD4+/CD8+ T cell ratio remained stable throughout SELECT and SELECTION.”

By Week 52 of SELECT, compared with baseline, mean CD56^bright NK counts expanded by approximately 5-fold and median Tregs declined by 58.4%, the authors reported.

“In patients receiving 2 years of continuous treatment with DAC HYP 150mg SC, the increase in CD56^bright NK cells and reductions in Treg, CD4+, and CD8+ cells reached a plateau at the end of Year 1 and did not progress indefinitely,” they reported.