Biogen and AbbVie Present New Data Showing Zinbryta, an RRMS Drug Candidate, Aids Cognition Without Immune Depletion

New data presented by Biogen and AbbVie at the recent 68th annual meeting of the American Academy of Neurology (AAN) showed that Zinbryta (daclizumab high-yield process) improved cognitive outcome measures in patients with relapsing forms of multiple sclerosis (RMS).

Additional results — from post-hoc analyses of clinical trials — also offer a better understanding of Zinbryta’s targeted mechanism of action, showing the drug does not cause a broad depletion of immune cells and that its effects on total lymphocyte counts were reversible 8 to 12 weeks after treatment discontinuation.

Zinbryta (daclizumab HYP) is a compound being developed by Biogen and AbbVie for the treatment of relapsing-remitting multiple sclerosis (RRMS). It consists of a humanized monoclonal antibody that binds to the receptor subunit CD25 of interleukin-2 (IL-2), highly expressed in immune T-cells. These immune cells are overly expressed in MS, and Zinbryta is thought to deplete the overly activated cells and, in turn, increase those cells that regulate the immune response (NK cells). A Phase 3 trial, DECIDE, was designed to compare clinical results of subcutaneously delivered Zinbryta (every four weeks) and a commonly used intramuscular injection (IM) of interferon beta-1a (Avonex).

“We are pleased to present additional analyses from the ZINBRYTA clinical program. This work provides important insights into the immunology behind ZINBRYTA,” said Michael Severino, MD, executive vice president, research and development, and chief scientific officer, AbbVie, in a press release. “We are very encouraged by the results we have seen from ZINBRYTA and are focused on bringing a potential new treatment option to patients who suffer from this devastating disease.”

Post-hoc analyses of DECIDE’s exploratory efficacy endpoints demonstrated that patients treated with Zinbryta had a statistically significant improvement in cognitive functioning. New results from 144 weeks of treatment demonstrated superior improvements from baseline in patients treated with Zinbryta on the Symbol Digit Modalities Test (a test that assesses attention and visual information processing speed) compared to those given Avonex.

“ZINBRYTA is an investigational therapy that is thought to work by regulating inflammation without broadly depleting the immune system — an important consideration for people living with the disease,” said Ralph Kern, MD, senior vice president, Worldwide Medical, Biogen. “ZINBRYTA has been shown to increase certain types of immunoregulatory cells and reduce cells that contribute to neurological injury caused by multiple sclerosis (MS).”

A post-hoc analysis from the SELECT program of Phase 2 trials assessed Zinbryta’s effects on total and differential counts of lymphocytes in patients who were treated for two years, and from its one-year extension (SELECTION) study, in treated patients randomly assigned to a 24-week washout period before returning to Zinbryta treatment at a previous dose level.

Data again demonstrated that Zinbryta has a reversible effect on immune cells without causing broad immune cell depletion. Specifically, results showed:

• Total lymphocyte counts return to baseline levels after 8 to 12 weeks of treatment discontinuation
• All studied cell counts measured returned to baseline values in SELECT within 6 months of treatment discontinuation
• Treatment increased CD56^bright  NK, a molecule that regulates immune cells, with mean counts at SELECT’s end showing about a five-fold increase
• The drug’s immunomodulatory mechanism of action was further verified, with an absence of broad depletion of total lymphocytes, CD4+, and CD8+ T-cells

Results from a safety post-hoc analysis of  the DECIDE study also found that 94 percent of cutaneous adverse events (AEs) related to Zinbryta treatment were mild or moderate in severity. Serious cutaneous AEs occurred in 2 percent of the treated patients, and were clinically resolved with antihistamines, topical and/or systemic steroids, other therapies, or treatment discontinuation.

A complete list of Zinbryta presentations made at the AAN meeting, held April 15–21 in Vancouver, Canada, are available through this link.