Zinbryta™ (daclizumab) – New Drug Approval

• On May 27, 2016, the FDA announced the approval of Biogen and AbbVie’s Zinbryta (daclizumab), 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.

• MS is a chronic, inflammatory, autoimmune disease of the central nervous system that disrupts communication between the brain and other parts of the body. It is among the most common causes of neurological disability in young adults and occurs more frequently in women than men.

— For most people with MS, episodes of worsening function (relapses) are initially followed by recovery periods (remissions). Over time, recovery may be incomplete, leading to progressive decline in function and increased disability.

• Zinbryta is a long-acting monoclonal antibody. Zinbryta works by binding to CD25, a subunit of the interleukin-2 (IL-2) receptor found on lymphocytes involved in the underlying biology of MS.

• The safety and efficacy of Zinbryta were based on two clinical trials. One study compared Zinbryta 150 mg monthly to Avonex® (interferon beta-1a) 30 mcg weekly in 1,841 patients for 144 weeks. The second study compared Zinbryta to placebo in 412 patients for 52 weeks. The primary outcome measure in both studies was the annualized relapse rate (ARR).

— Zinbryta had a statistically significant effect on the ARR compared to Avonex (0.216 vs. 0.393; 45% relative reduction in ARR, p < 0.0001). — Zinbryta had a statistically significant effect on the ARR compared to placebo (0.211 vs. 0.458; 54% relative reduction in ARR, p < 0.0001).

• Zinbryta carries a boxed warning for hepatic injury including autoimmune hepatitis and other immune- mediated disorders.

— Zinbryta is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Zinbryta REMS Program, because of the risks described in the boxed warning.

• Zinbryta is contraindicated in those with pre-existing hepatic disease or hepatic impairment, including alanine aminotransferase (ALT) or aspartate aminotransferase (AST) at least 2 times the upper limit of normal; history of autoimmune hepatitis or other autoimmune condition involving the liver; and history of hypersensitivity to daclizumab or any other components of the formulation – use in such patients may result in anaphylaxis or life-threatening multi-organ hypersensitivity.

• Other warnings and precautions of Zinbryta include acute hypersensitivity, infections, and depression and suicide.

Continued . . .

• The most common adverse events (≥ 5% and ≥ 2% higher than comparator) with Zinbryta use 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 ALT compared with placebo.

• The recommended dose of Zinbryta is 150 mg injected subcutaneously once monthly.

— Hepatic function and assessment for tuberculosis and other infections should be evaluated prior to initiating Zinbryta therapy. — Avoid initiating Zinbryta in patients with tuberculosis or other severe active infection.

• Biogen and AbbVie plan to launch Zinbryta within a few weeks. Zinbryta will be available as a 150 mg/mL solution in a single-dose prefilled syringe for self-administration.

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