FDA Approves Zinbryta™ (Daclizumab) for Relapsing Forms of Multiple Sclerosis
Approval and Medication Overview
Late on Friday, May 27, 2016, the United States Food and Drug Administration announced the approval of Zinbryta™ (daclizumab) for adults with relapsing forms of multiple sclerosis (RMS). This monoclonal antibody is self-administered subcutaneously (under-the-skin) once per month and has been shown to reduce the number of relapses as well as new or newly enhancing lesions, as compared to another approved MS medication and to placebo, in two separate studies. Zinbryta is co-promoted in the United States by Biogen and AbbVie.
While the FDA approved Zinbryta because they determined that the benefits outweigh the potential for adverse events, this medication does carry safety risks, which include liver injury and immune conditions. Monthly liver-function tests are required with Zinbryta. The FDA states, “Zinbryta should generally be used only in patients who have had an inadequate response to two or more MS drugs. Zinbryta has a boxed warning and is available only through a restricted distribution program under a Risk Evaluation and Mitigation Strategy.”
According to the 2016 edition of the MS Research Update (published jointly by the Multiple Sclerosis Association of America, the Consortium of Multiple Sclerosis Centers, and the International Organization of MS Nurses), “Daclizumab (Zinbryta) is a genetically engineered monoclonal antibody that binds to CD25, a receptor on T cells that is thought to become activated in response to MS. Daclizumab is believed to work by selectively targeting these activated T cells without causing general T-cell depletion. It is approved by the FDA for use in rheumatoid arthritis and other autoimmune diseases.”
Zinbryta is the 14th disease-modifying therapy to be approved for the long-term treatment of relapsing forms of MS. It is the first approved medication for MS that is self-administered subcutaneously (under-the-skin) once per month, versus the other approved self-administered medications that are given more frequently (ranging from once every two weeks to once daily). Zinbryta is also the first monoclonal antibody approved for MS that may be self-administered at home by subcutaneous injection, versus an intravenous (IV) infusion, which often requires going to an infusion center.
The United States is the first country to approve Zinbryta for the long-term treatment of relapsing forms of MS. According to Biogen and AbbVie, “The European Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) recently granted a positive opinion for Zinbryta. The opinion of the CHMP has been referred to the European Commission for final decision on approval. Zinbryta is also currently under regulatory review in Switzerland, Canada, and Australia.”
Clinical Trials and Results
The FDA evaluated the effectiveness and safety of Zinbryta according to the results of two clinical trials. The larger, Phase III DECIDE study compared Zinbryta to Avonex® (interferon beta-1a) in 1,841 participants who were studied for two-to-three years. Biogen and AbbVie note that DECIDE was a global, randomized, double-blind, multicenter study in patients with relapsing forms of multiple sclerosis (RMS) designed to determine if Zinbryta would provide superior outcomes for certain clinical endpoints.
The smaller SELECT trial was a Phase IIb study comparing Zinbryta to placebo in 621 participants who were treated for one year. SELECT was a multicenter, randomized, double-blind, study that evaluated the efficacy and safety of Zinbryta in two dose levels, with 208 participants with RMS receiving 150 mg and 209 participants with RMS receiving 300 mg via subcutaneous injection every four weeks, versus 204 participants with RMS receiving placebo. Please note that the FDA lists 412 participants for this study, due to the fact that the FDA did not include the 209 participants taking the higher dose of Zinbryta, which was not submitted for approval. Study results listed in this article are limited to those in the lower-dose group.
In the DECIDE study, individuals taking Zinbryta experienced a 45-percent reduction in annualized relapse rate (ARR) compared to individuals taking Avonex for up to 144 weeks. Results from this study also showed that participants taking Zinbryta had a significant reduction in new or newly enlarging T2-hyperintense lesions by 54 percent, compared to Avonex at 96 weeks. Additionally, 67 percent of participants taking Zinbryta for up to 144 weeks were relapse-free, compared to 51 percent of the individuals who were given Avonex.
In the SELECT study, individuals taking 150-mg Zinbryta experienced a 54-percent reduction in annualized relapse rate (ARR) compared to individuals taking placebo for up to 52 weeks (one year). According to the 2016 edition of the MS Research Update, compared to placebo, individuals in the 150-mg group in the SELECT study experienced the following results: the number of new gadolinium-enhancing lesions was reduced by 69 percent; the number of new or newly enlarging T2-hyperintense lesions was reduced by 70 percent; and the proportion of patients who relapsed was reduced by 50 percent. Sustained disability progression at one year was reduced by 57 percent.
Adverse Reactions and Boxed Warning
The FDA lists a different set of adverse reactions for each of the two trials. In the DECIDE study, the most common adverse reactions reported by patients receiving Zinbryta (versus Avonex) were cold symptoms, upper-respiratory-tract infection, rash, influenza, dermatitis, throat pain, eczema, and enlargement of lymph nodes. In the SELECT study, the most common adverse reactions reported by patients receiving Zinbryta (versus placebo) were depression, rash, and increased alanine aminotransferase (measuring the amount of liver enzymes in the blood).
As noted earlier, the FDA requires Zinbryta to have a boxed warning. The FDA explains, “The boxed warning tells prescribers that the drug can cause severe liver injury, including life-threatening and fatal events. Health care professionals should perform blood tests to monitor the patient’s liver function prior to starting Zinbryta, monthly before each dose, and for up to six months after the last dose. The boxed warning also highlights other important risks of Zinbryta treatment including immune conditions, such as inflammation of the colon (non-infectious colitis), skin reactions, and enlargement of lymph nodes (lymphadenopathy). Additional highlighted warnings include hypersensitivity reactions (anaphylaxis or angioedema), increased risk of infections, and symptoms of depression and/or suicidal ideation.”
Response from Jack Burks, MD
MSAA Chief Medical Officer Dr. Jack Burks comments, “I am pleased to see Zinbryta as an option for treating relapsing MS patients. A once-a-month subcutaneous injection (self-injected just under the skin) of a monoclonal antibody (MAB) with superior efficacy to interferon beta-1a (Avonex) is very encouraging. I was further encouraged by the results obtained from the relatively specific target of just one T cell (CD25) while sparing other lymphocytes that are needed to protect us from illnesses and infection.
“The FDA’s ‘black box warning’ is related to the 6-percent risk of increased liver enzymes in the blood of Zinbryta-treated patients, compared to the 3-percent increase in liver enzymes in the placebo group. Fortunately, no fatalities were related to liver damage. Nonetheless, the Zinbryta-treated patients must have liver-enzyme tests performed monthly.”
For More Information
Extra support for individuals taking or interested in taking Zinbryta will be provided through Biogen’s Above MS™ program. To learn more about the Above MS program, please call (800) 456-2255, Monday through Friday, 8:30 am to 8:00 pm ET. For more information on this medication, including prescribing information and the boxed warning, individuals may visit www.ZINBRYTA.com.
For more information or to speak with a trained MSAA Client Services Specialist, please call MSAA’s Helpline at (800) 532-7667, extension 154. Questions to MSAA’s Client Services department may also be emailed to MSquestions@mymsaa.org. Information on other approved disease-modifying therapies for relapsing forms of MS may be found on this website (at mymsaa.org) by selecting “Treatments” under “MS Information.”
Written by Susan Wells Courtney, MSAA Senior Writer
Reviewed by Jack Burks, MD, MSAA Chief Medical Officer