FDA approves Zinbryta to treat multiple sclerosis.

May 27, 2016

The U.S. Food and Drug Administration today approved Zinbryta (daclizumab) for the treatment of adults with relapsing forms of multiple sclerosis (MS). Zinbryta is a long-acting injection that is self- administered by the patient monthly.

Daclizumab is a humanized monoclonal antibody that binds to the alpha subunit of the interleukin-2 receptor (IL-2Rα, CD25). Daclizumab is composed of two humanized gamma-1 heavy chains and two humanized kappa light chains and has a molecular weight of approximately 144 kilodaltons (kDa).

CLINICAL PHARMACOLOGY

 Mechanism of Action

The precise mechanism by which daclizumab exerts therapeutic effects in multiple sclerosis is unknown but is presumed to involve modulation of IL-2 mediated activation of lymphocytes through binding to CD25, a subunit of the high-affinity IL-2 receptor.

INDICATIONS AND USAGE

ZINBRYTA is an interleukin-2 receptor blocking antibody indicated for the treatment of adult patients with relapsing forms of multiple sclerosis (MS). 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.

DOSAGE AND ADMINISTRATION

  • Recommended dosage: 150 milligrams once monthly
  •  For subcutaneous use only
  •  Train patients in the proper technique for self-administration.
  • Conduct laboratory tests at baseline and at periodic intervals to monitor for early signs of potentially serious adverse reactions.

SAFETY & EFFICACY

The effectiveness of Zinbryta was shown in two clinical trials. One trial compared Zinbryta and Avonex in 1,841 participants who were studied for 144 weeks. Patients on Zinbryta had fewer clinical relapses than patients taking Avonex. The second trial compared Zinbryta with placebo and included 412 participants who were treated for 52 weeks. In that study, those receiving Zinbryta had fewer relapses compared to those receiving placebo.

Zinbryta should generally be used only in patients who have had an inadequate response to two or more MS drugs because Zinbryta has serious safety risks, including liver injury and immune conditions. Because of the risks, Zinbryta has a boxed warning and is available only through a restricted distribution program under a Risk Evaluation and Mitigation Strategy.

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).

CONTRAINDICATIONS

  • Pre-existing hepatic disease or hepatic impairment, including ALT or AST at least 2 times the ULN
  • History of autoimmune hepatitis or other autoimmune condition involving the liver
  • History of hypersensitivity to daclizumab or any other component of the formulation

 WARNINGS AND PRECAUTIONS

  •  Hypersensitivity Reactions: Risk of anaphylaxis and angioedema. Discontinue and do not re-start ZINBRYTA if anaphylaxis or other allergic reactions occur
  • Infections: Increased risk of infections. If serious infection develops, consider withholding ZINBRYTA until infection resolves
  • Depression and Suicide: Advise patients to immediately report symptoms of depression and/or suicidal ideation to their health care provider.
  • Consider discontinuation if severe depression and/or suicidal ideation occur.

ADVERSE REACTIONS

The most common adverse reactions (incidence ≥5% and ≥2% higher incidence than comparator) reported for ZINBRYTA were nasopharyngitis, upper respiratory tract infection, rash, influenza, dermatitis, oropharyngeal pain, bronchitis, eczema and lymphadenopathy compared with AVONEX; and upper respiratory tract infection, depression, rash, pharyngitis, and increased alanine aminotransferase (ALT) compared with placebo.

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