Biogen, one of the world’s oldest independent biotechnology companies, and AbbVie, a global, research-based biopharmaceutical company, announced that the European Commission (EC) has granted marketing authorization for Zinbryta (daclizumab) for the treatment of adult patients with relapsing forms of multiple sclerosis (RMS). Zinbryta is a once-monthly, self-administered, subcutaneous injection.
“Clinical data showed Zinbryta significantly reduced relapses, 24-week confirmed disability progression and new brain lesions for up to three years compared to Avonex (interferon beta-1a) intramuscular injection, providing a valuable new option for people with RMS,” said Professor Gavin Giovannoni, Chair of Neurology, Blizard Institute, Barts and The London School of Medicine and Dentistry. “Zinbryta has an immunomodulatory mechanism of action (MOA) that regulates inflammation without broadly depleting the immune system, and immune cell effects are reversible within six months. This offers an alternative approach to treating multiple sclerosis (MS) and is an important consideration when deciding how to sequence therapies throughout the course of a patient’s disease.”
The EC approval of Zinbryta is supported by results from two studies, including DECIDE, the largest and longest head-to-head phase 3 study ever conducted in MS. The phase 2b SELECT and phase 3 DECIDE studies were global, randomized, double-blind, controlled studies that involved approximately 2,400 people living with RMS. Some patients in DECIDE were treated for up to three years.
In DECIDE and SELECT, Zinbryta significantly reduced patients’ annualized relapse rate (ARR), the primary endpoint of the studies, by 45 per cent compared to Avonex up to 144 weeks and by 54 per cent compared to placebo at 52 weeks (both p<0.0001), respectively. Analyses of these studies demonstrated the consistent effect of Zinbryta relative to placebo and Avonex across various subgroups of patients defined by demographic and MS disease characteristics.
“With the approval of Zinbryta in the European Union, we are providing a much needed treatment option for people living with MS,” said Michael Severino, executive vice president, research and development and chief scientific officer, AbbVie. “This is an important part of AbbVie’s ongoing commitment to advancing neuroscience research specifically in the area of MS.”
“Zinbryta is an important new once-monthly option for people with RMS, including those whose disease activity has been insufficiently controlled by their prior therapy,” said Alfred Sandrock, executive vice president and chief medical officer at Biogen. “MS manifests differently in each person, with varied symptoms and progressions; therefore, it is important that people living with the disease have treatment choices to address their diverse and evolving needs.”
Zinbryta’s MOA is thought to block the activation of autoreactive T-cells, a major contributor to inflammation in the nervous system of people with MS. Zinbryta leads to an increase in immunoregulatory CD56bright natural killer (NK) cells, which have been shown to selectively decrease activated T-cells that contribute to the nerve injury caused by MS. These immunomodulatory effects of Zinbryta are believed to reduce central nervous system pathology in MS and thereby reduce the occurrence of relapse and disability progression.
During Zinbryta treatment, mean cell counts for the major immune subsets (T, B, and NK cells) remained within normal ranges; total lymphocyte, T and B cell counts decreased on average =10 per cent from baseline during the first year of treatment.
Total lymphocyte counts returned to baseline within approximately eight to 12 weeks after the last dose, and all other cell counts studied returned to baseline within approximately 20 to 24 weeks after the last dose.
DECIDE was a two- to three-year, phase 3, 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 compared to treatment with Avonex (interferon beta-1a) 30 mcg intramuscular (IM) injection. DECIDE was an active comparator study with two groups: 150 mg of subcutaneous Zinbryta every four weeks (n=919) was compared to Avonex IM once weekly (n=922).
SELECT was a multicenter, randomized, double-blind, phase 2b study that evaluated the efficacy and safety of Zinbryta 150 mg (n=208) and 300 mg (n=209) subcutaneous every four weeks for one year versus placebo (n=204) in patients with relapsing forms of multiple sclerosis (RMS).
Zinbryta is being developed globally for relapsing forms of multiple sclerosis (RMS). The recommended dosage of Zinbryta is 150 mg, self-administered subcutaneously on a monthly basis. Zinbryta is also approved in the United States and is under regulatory review in Switzerland, Canada and Australia.
In clinical trials, Zinbryta demonstrated superior efficacy in relapse reduction and MRI, key measures of MS disease activity, compared to Avonex (interferon beta-1a) intramuscular injection and placebo. In the EU, an educational program to inform physicians and patients about the risk of severe hepatic injury and the procedures related to the appropriate management of this risk to minimize its occurrence and its severity.
Zinbryta is a humanized IgG1 monoclonal antibody that selectively binds to the high-affinity interleukin-2 (IL-2) receptor subunit (CD25). CD25 is expressed at high levels on T-cells that become activated in people with MS.