Disease-modifying therapies (DMTs) are important tools in the fight against multiple sclerosis. To date, the U.S. Food and Drug Administration (FDA) has approved 14 DMTs: 13 therapies for the treatment of relapsing forms of MS, some of which are also approved for clinically isolated syndrome; and one therapy, Novantrone, for the treatment of “worsening MS;” however, Novantrone is no longer customarily used in the United States.
In May 2016, daclizumab (under the brand name, Zinbryta) was approved by the FDA as the fourteenth DMT option for people diagnosed with MS in the U.S. In July 2016, Zinbryta was approved for use in Europe. The FDA suggests that because of its safety profile, the use of Zinbryta should generally be reserved for patients who have had an inadequate response to two or more drugs indicated for the treatment of MS. Editor's note: On March 2, 2018, Zinbryta was taken off the market by Biogen and AbbVie.
Daclizumab has been on the market before under another brand name — Zenapax — with a different drug delivery system. But that drug was pulled from the market by its drug manufacturer, Roche, in 2009, due to lack of demand.
What is Zinbryta?
According to the prescribing information and published studies on the topic (see the Sources list below), Zinbryta (daclizumab high-yield process, or DAC-HYP) is an interleukin-2 receptor (IL-2R) blocking monoclonal antibody indicated for the treatment of adults with relapsing forms of MS, developed by Biogen and Abbvie. The drug is supplied in a single-dose prefilled syringe (150 mg/mL) that is given once monthly by subcutaneous injection.
It should be stored in the refrigerator in the original container to protect from light. It must not be frozen or exposed to high temperatures above 86°F. You should allow Zinbryta to reach room temperature before injecting; however, do not place it back into the refrigerator for storage after allowing it to warm to room temperature. It can be stored at room temperature, protected from light, for up to 30 days.
How does the drug work?
DAC-HYP Daclizumab is a humanized IgG1 monoclonal antibody that binds to the αlpha subunit (CD25) of IL-2R expressed on activated T lymphocytes. Researchers originally thought that daclizumab demonstrated anti-inflammatory properties by binding directly to CD25 on activated T cells; however, alternative mechanisms of action have been identified. Daclizumab increases the number of immunoregulatory CD56bright natural killer (NK) cells. It promotes the differentiation of innate lymphoid precursor cells away from pro-inflammatory lymphoid tissue inducer cells. Daclizumab may also prevent mature dendritic cells from activating T cells. Activated T cells are one of the type of cells that cause damage in MS.
Is Zinbryta the same medication as Zenapax?
Zenapax (daclizumab) was an intravenous medication approved to prevent acute rejection to kidney transplants, but as previously mentioned, left the market in 2009. Early studies of daclizumab in multiple sclerosis were conducted using intravenous Zenapax. The controlled clinical trials leading to FDA approval for MS were conducted using subcutaneous Zinbryta.
How effective is the drug?
In two randomized, double-blind, controlled clinical trials, daclizumab (Zinbryta) was shown to be more effective in reducing the frequency of relapses and reducing the development of brain lesions compared to placebo or interferon beta-1a (brand name, Avonex) in patients with relapsing-remitting MS.
In a three-year study, 919 people who used daclizumab had 45 percent fewer relapses compared to 922 people who used interferon beta-1a. The average number of new or newly enlarging T2 hyperintense lesions also were reduced by 54 percent. Sixty-seven percent of patients taking daclizumab were relapse-free compared with 51 percent of people using interferon beta-1a. Improvement in disability progression was not statistically significant.
In a 1-year clinical trial, 208 people treated with daclizumab had 54 percent fewer relapses compared to 204 people who took placebo. Eighty-one percent of patients taking daclizumab were relapse-free compared with 64 percent taking placebo. The average number of new or newly enlarging T2 hyperintense lesions and new T1 Gd-enhancing lesions were reduced by 70 and 69 percent, respectively, in people using daclizumab. Twelve-week confirmed disability progression was reduced by 57 percent in people using daclizumab compared to placebo.
What are the side effects or safety concerns of daclizumab (Zinbryta)?
In an analysis of six clinical studies, researchers report that 84 percent of 2,236 daclizumab-treated patients experienced at least one adverse event (AE), the most of which were mild or moderate in severity. Twelve percent of patients experienced a severe AE. Forty-one percent of side effects were connected to treatment and about 15 percent of patients discontinued treatment or withdrew from the studies due to AEs.
Daclizumab can cause serious side effects: serious liver problems (including autoimmune-related liver problems) that may lead to death and other immune-mediated disorders or immune system problems. During clinical trials, one patient experienced a serious rash and died due to ischemic colitis that occurred as a complication of a psoas abscess; another died of liver failure due to autoimmune hepatitis.
The most common side effects of daclizumab include: upper respiratory tract infection, flu, pain or swelling in the nose, throat, or mouth, bronchitis, abnormal liver function tests, dry itchy, scaly, or inflamed skin (eczema), rash, depression and depressed mood, swollen lymph glands.
Who should not use it?
Patients with preexisting liver disease, liver impairment (e.g. liver enzymes measured at 5 times the upper normal limit), or history of autoimmune hepatitis or other autoimmune condition involving the liver should not use daclizumab.
Is the drug safe to use during pregnancy?
Data on pregnancies exposed to daclizumab is limited but do not suggest an increased risk of preterm birth or adverse fetal or maternal outcomes. In human clinical trials, there were 38 pregnancies exposed to daclizumab. Among those were 20 live births, four spontaneous abortions or miscarriages, eight elective terminations, and two ectopic pregnancies. The spontaneous abortions occurred early in pregnancy (>= 10 weeks’ gestation) at a rate consistent with early pregnancy loss in the general population.
See more helpful articles:
Cohan S. Therapeutic efficacy of monthly subcutaneous injection of daclizumab in relapsing multiple sclerosis. Biologics: Targets & Therapy. 2016;10:119-138. doi:10.2147/BTT.S89218.
Giovannoni G, Kappos L, Gold R, et al. Safety and tolerability profile of daclizumab in patients with relapsing-remitting multiple sclerosis: An integrated analysis of clinical studies. Mult Scler Rel Disord. 2016;9:36-46.
Gold R, Stefoski D, Selmaj K, et al. Pregnancy Experience: Nonclinical Studies and Pregnancy Outcomes in the Daclizumab Clinical Study Program. Neurol Ther. 2016 Jul 13. [Epub ahead of print]
Milo R. The efficacy and safety of daclizumab and its potential role in the treatment of multiple sclerosis. Ther Adv Neurol Disord. 2014;7(1):7-21. doi: 10.1177/1756285613504021.
Morton, CC. The Paradox of Daclizumab. Multiple Sclerosis Discovery Forum. 2014. doi/10.7493/msdf.10.13945.1
Zinbryta Prescribing Information accessed at Zinbryta.com.